Background

KEYNOTE-355 (NCT02819518) evaluated pembro + chemo vs pbo + chemo in previously untreated patients (pts) with locally recurrent inoperable or metastatic TNBC. Pembro + chemo improved the PFS and OS in pts with PD-L1 combined positive score (CPS) ≥10 disease. We present results for patient-reported outcome (PRO) measures among pts with PD-L1 CPS ≥10.

Methods

Pts were randomized 2:1 to pembro 200 mg or pbo Q3W for up to 35 cycles + chemo (investigator’s choice of nab-paclitaxel, paclitaxel, or gemcitabine/carboplatin). QLQ-C30 (including global health status/quality of life [GHS/QoL]) and physical and emotional functioning scales), QLQ-BR23, and EQ-5D visual analogue scale (VAS) were prespecified. PROs were assessed at baseline, during treatment, and the 30-day safety follow-up visit and analyzed for pts who received ≥1 dose of study treatment and completed ≥1 PRO assessment. Change in PRO scores from baseline were assessed at wk 15 (latest timepoint at which completion/compliance rates were ≥60%/≥80%; negative values favor the pembrolizumab group). Time to deterioration (TTD) in PROs was defined as time to first onset of ≥10-point worsening in score from baseline.

Results

These PRO analyses included 317 pts with PD-L1 CPS ≥10 (pembro + chemo; n = 217; pbo + chemo, n = 100). Completion/compliance at wk 15 was 77.0%/87.0% with pembro + chemo and 70.0%/81.4% with pbo + chemo. There were no between-group differences in change from baseline to wk 15 in the QLQ-C30 GHS/QoL, emotional functioning, physical functioning, or the EQ-5D VAS scale scores, and no between-group difference in TTD in QLQ-C30 GHS/QoL, emotional functioning, or physical functioning (Table). Analyses by QLQ-BR23 showed no decrease in HRQoL with pembro + chemo vs pbo + chemo. Table: 164O

Conclusions

Addition of pembro to chemo did not result in a decrease in HRQoL in pts with previously untreated, PD-L1–positive (CPS ≥10) advanced, TNBC.

Clinical trial identification

NCT02819518, EudraCT 2016-001432-35.

Editorial acknowledgement

Additional support was provided by Wilbur Panof Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Medical writing assistance was provided by Kara Nyberg, PhD, of ICON plc (Blue Bell, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme Corp.

Funding

Merck Sharp & Dohme Corp.

Disclosure

D.W. Cescon: Financial Interests, Personal, Consultancy/Advisory role: AstraZeneca, Exact Sciences, Eisai, Gilead, GlaxoSmithKline, Merck, Novartis, Pfizer Roche; Financial Interests, Institutional, Research Funding: GlaxoSmithKline, Inivata, Merck, Pfizer, Roche; Other: is a member of a trial steering committee for AstraZeneca, Merck and GlaxoSmithKline; Other: holds a holds a patent (US62/675,228) for methods of treating cancers characterized by a high expression level of spindle and kinetochore associated complex subunit 3 (ska3) gene. P. Schmid: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, Pfizer, Puma, Roche, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Astellas, AstraZeneca, Genentech, Novartis, Oncogenex, Roche; Other, Spouse - Employee: Roche. H.S. Rugo: Financial Interests, Personal, Invited Speaker: Puma; Financial Interests, Personal, Advisory Board: Samsung; Financial Interests, Personal, Invited Speaker: Mylan; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Invited Speaker: Lilly; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: OBI Pharma; Financial Interests, Institutional, Invited Speaker: Immunomedics; Financial Interests, Institutional, Invited Speaker: Macrogenics; Financial Interests, Institutional, Invited Speaker: Daiichi; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker: Merck; Financial Interests, Institutional, Invited Speaker: Odonate; Financial Interests, Institutional, Invited Speaker: Sermonix; Financial Interests, Institutional, Invited Speaker: Seattle Genetics; Financial Interests, Institutional, Invited Speaker: Polyphor; Financial Interests, Institutional, Invited Speaker: Boehringer Ingelheim; Non-Financial Interests, Advisory Role, I advise a number of companies without compensation: various. S-A. Im: Financial Interests, Personal, Consulting/Advisory role: Amgen, AstraZeneca, Eisai, Hanmi, Lilly, Medpacto, Inc., Novartis, Pfizer, Roche/Genentech; Financial Interests, Personal, Research Funding: AstraZeneca, Pfizer, Roche/Genentech; Financial Interests, Personal, Other, Travel, accommodations, expenses: Novartis; Roche/Genentech; Financial Interests, Personal, Other: Roche. M. Md Yusof: Financial Interests, Personal, Honoraria: AstraZeneca, Bayer, Boehringer Ingelheim, Merck, MSD, Specialised Therapeutics, Zuellig Pharma, Novartis, Pfizer, Roche, Eisai, Celgene; Financial Interests, Institutional, Research grant: Astellas, AstraZeneca, Arcus, Genentech, Mundi Pharma, Novartis, Pfizer, Roche. C.E. Gallardo: Financial Interests, Personal, Consulting/Advisory role: Lilly, MSD, Roche; Financial Interests, Personal, Speakers Bureau: Bristol Myers Squibb; Financial Interests, Personal, Research Funding: Novartis Pharma SAS, Roche; Financial Interests, Personal, Other, Travel, accommodations, expenses: MSD, Roche. C.H. Barrios: Financial Interests, Personal, Consulting/Advisory role: Boehringer Ingelheim, Eisai Europe Ltd., GlaxoSmithKline, Novartis Pharma SAS, Pfizer Pharmaceuticals Israel, Roche/Genentech; Financial Interests, Personal, Research Funding: AB Science, Abraxis BioScience, Amgen, Asana Biosciences, Astellas Pharma, AstraZeneca, Biomarin, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Exelixis, GlaxoSmithKline, ImClone Systems, Investigator in AbbVie-sponsored cl. Trials, LEO Pharma, Lilly, Medivation, Merck, Merrimack, Millennium, Mylan, Novartis Pharma SAS, Pfizer Pharmaceuticals Israel, Roche/Genentech, Sanofi, Taiho Pharmaceutical. J.M. Perez Garcia: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Expert Testimony: Eisai. H. Iwata: Financial Interests, Personal, Advisory Board: Chugai; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Taiho; Financial Interests, Personal and Institutional, Invited Speaker: Chugai; Financial Interests, Personal and Institutional, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca; Financial Interests, Personal and Institutional, Invited Speaker: MSD; Financial Interests, Personal and Institutional, Invited Speaker: Amgen; Financial Interests, Personal and Institutional, Invited Speaker: Sanofi; Financial Interests, Personal and Institutional, Invited Speaker: Lilly; Financial Interests, Personal and Institutional, Invited Speaker: Novartis; Financial Interests, Personal and Institutional, Invited Speaker: Bayer; Financial Interests, Personal and Institutional, Invited Speaker: Pfizer; Financial Interests, Personal and Institutional, Invited Speaker: Kyowa Hakko Kirin; Financial Interests, Personal and Institutional, Invited Speaker: Behringer; Financial Interests, Personal and Institutional, Invited Speaker: Nihon Kayaku. N. Masuda: Financial Interests, Other, Leadership: Japan Breast Cancer Research Group Association (JBCRG); Financial Interests, Personal, Honoraria: AstraZeneca, Chugai Pharma, Eisai, Lilly Japan, Pfizer; Financial Interests, Institutional, Research Funding: AstraZeneca, Chugai Pharma, Daiichi Sankyo, Eisai, Eli Lilly, Kyowa-Kirin, MSD, Novartis, Pfizer, Sanofi. E. Gokmen: Financial Interests, Other: Eli Lilly, Janssen Oncology, Novartis, Pfizer, Roche; Financial Interests, Personal, Consulting/Advisory Role: Lilly, Novartis, Pfizer, Roche; Financial Interests, Personal, Speaker Bureau: Lilly, Novartis, Pfizer, Roche; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: BMS, MSD Oncology, Novartis, Pfizer, Roche. S. Loi: Financial Interests, Institutional, Expert Testimony, Consultant: Aduro Biotech; Financial Interests, Institutional, Advisory Board, Consultant: Novartis; Financial Interests, Institutional, Advisory Board, Consultant: GlaxoSmithKline; Financial Interests, Institutional, Advisory Board, Consultant: Roche Genentech; Financial Interests, Institutional, Advisory Board, Consultant: AstraZeneca; Financial Interests, Institutional, Advisory Board, Consultant: Silverback Therapeutics; Financial Interests, Institutional, Advisory Board, Consultant: G1 Therapeutics; Financial Interests, Institutional, Expert Testimony, Consultant: Puma Biotechnologies; Financial Interests, Institutional, Expert Testimony, Consultant: Pfizer; Financial Interests, Institutional, Expert Testimony, Consultant: Seattle Genetics; Financial Interests, Institutional, Expert Testimony, Consultant: BMS; Financial Interests, Institutional, Funding, Research: Novartis; Financial Interests, Institutional, Funding, Research: BMS; Financial Interests, Institutional, Funding, Research: Merck; Financial Interests, Institutional, Funding, Research: Puma Biotechnology; Financial Interests, Institutional, Funding, Research: Eli Lilly; Financial Interests, Institutional, Funding, Research: Nektar Therapeutics; Financial Interests, Institutional, Funding, Research: AstraZeneca; Financial Interests, Institutional, Funding, Research: Seattle Genetics; Financial Interests, Institutional, Funding, Research: Roche - Genentech; Non-Financial Interests, Advisory Role, Consultant (Non remunerated): Seattle Genetics; Non-Financial Interests, Advisory Role, Consultant (Non remunerated): Novartis; Non-Financial Interests, Advisory Role, Consultant (Non remunerated): Bristol Myers Squibb; Non-Financial Interests, Advisory Role, Consultant (Non remunerated): Merck; Non-Financial Interests, Advisory Role, Consultant (Non remunerated): AstraZeneca; Non-Financial Interests, Advisory Role, Consultant (Non remunerated): Roche Genentech. A. Haiderali, Z. Guo, A. Martin Nguyen: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.; Financial Interests, Personal, Ownership Interest, Stock and Other Ownership Interests: Merck & Co., Inc. X. Zhou: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. J. Cortés: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal, Advisory Board: Cellestia; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Erytech; Financial Interests, Personal, Advisory Board: Athenex; Financial Interests, Personal, Advisory Board: Polyphor; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: LEUKO; Financial Interests, Personal, Advisory Board: Bioasis; Financial Interests, Personal, Advisory Board: Clovis oncology; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Celgene; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Samsung Bioepis; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Merck Sharp & Dohme; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Ellipses; Financial Interests, Personal, Advisory Board: Hibercell; Financial Interests, Personal, Advisory Board: BioInvent; Financial Interests, Personal, Advisory Board: Zymeworks; Financial Interests, Personal, Advisory Board: Gemoab; Financial Interests, Personal, Advisory Board: Gilead; Financial Interests, Personal, Advisory Board: Menarini; Financial Interests, Personal, Advisory Board: Reveal Genomics; Financial Interests, Personal, Stocks/Shares: MedSIR; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Stocks/Shares: Nektar Therapeutics; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Ariad Pharmaceuticals; Financial Interests, Institutional, Research Grant: Baxalta GMBH/Servier Affaires; Financial Interests, Institutional, Research Grant: Bayer healthcare; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: Guardanth Health; Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Piqur Therapeutics; Financial Interests, Institutional, Research Grant: Puma B; Financial Interests, Institutional, Research Grant: Queen Mary University of London; Other, Other, Travel cost and expenses: Roche; Other, Travel cost and expenses: Novartis; Other, Travel cost and expenses: Eisai; Other, Travel cost and expenses: Daiichi Sankyo. All other authors have declared no conflicts of interest.

Background

HER2 IHC1+ or IHC2+ and in situ hybridization (ISH)-negative results are sometimes referred to as HER2-Low. SG is a novel antibody-drug conjugate composed of an anti–Trop-2 antibody coupled to SN-38 via a proprietary, hydrolyzable linker. SG is approved in mTNBC for the second line (2L) onwards. In the ASCENT study, SG had significant progression-free survival (PFS) and overall survival (OS) benefit vs chemotherapy of physician’s choice (TPC). This ASCENT post hoc subgroup analysis evaluates SG efficacy in HER2 IHC0 and HER2-Low mTNBC.

Methods

Patients (pts) with mTNBC refractory/relapsing after ≥2 prior chemotherapies (≥1 in the metastatic setting) were randomized 1:1 to receive SG (10 mg/kg IV on d 1 and 8, every 21 d) or TPC (capecitabine, eribulin, vinorelbine, or gemcitabine) until unacceptable toxicity/progression. Primary endpoint was PFS per RECIST 1.1 by central review. Pts with known HER2-positive disease were ineligible, but HER2 status was not assessed centrally in ASCENT. Local HER2 IHC results were analyzed retrospectively.

Results

In the intent-to-treat (ITT) population (SG vs TPC), 149 vs 144, 63 vs 60, and 55 vs 58 pts had HER2 IHC0, HER2-Low, and missing HER2 IHC results, respectively; 79% of the ITT population was HER2-evaluable. Baseline characteristics between HER2 IHC0 vs HER2-Low were comparable and similar to the ITT population. Median PFS and OS were significantly improved, and objective response rate was numerically higher with SG vs TPC in the HER2 IHC0 and HER2-Low groups (Table). HER2-Low had numerically better outcomes vs HER2 ICH0 in both the SG and TPC arms.

Conclusions

Clinical benefit with SG in HER2 IHC0 and HER2-Low mTNBC was consistent with that of the ASCENT ITT population, regardless of HER2 status. SG should be considered an effective treatment option for pts with mTNBC eligible for 2L or later therapy. Table: 168P

Clinical trial identification

NCT02574455.

Editorial acknowledgement

Editorial support was provided by Yao Bian, PhD, of Team 9 Science and funded by Gilead Sciences, Inc.

Legal entity responsible for the study

Gilead Sciences, Inc.

Funding

Gilead Sciences, Inc.

Disclosure

S.A. Hurvitz: Financial Interests, Personal, Invited Speaker: Clinical Care Options; Financial Interests, Personal, Invited Speaker: aptitude health; Financial Interests, Personal, Invited Speaker: axis medical; Financial Interests, Personal, Invited Speaker: cancer expert now; Financial Interests, Personal, Invited Speaker: ICHE; Financial Interests, Personal, Invited Speaker: MJH Associates; Financial Interests, Personal, Invited Speaker: PER; Financial Interests, Personal, Invited Speaker: Primo; Financial Interests, Personal, Invited Speaker: Projects in Knowledge; Financial Interests, Personal, Invited Speaker: Prova Education; Financial Interests, Personal, Invited Speaker: Research to Practice; Financial Interests, Personal, Invited Speaker: Ultimate Medical Academy; Financial Interests, Personal, Invited Speaker: Vaniam; Financial Interests, Personal, Invited Speaker: WebMD; Financial Interests, Personal, Invited Speaker: Rockpointe; Financial Interests, Personal, Invited Speaker: OBR; Financial Interests, Personal, Invited Speaker: Peer Education; Financial Interests, Personal, Invited Speaker: Spire Learning; Financial Interests, Personal, Invited Speaker: PrecisCA; Financial Interests, Personal, Stocks/Shares, stock options: NK Max; Financial Interests, Personal, Stocks/Shares, spouse owns: ROM Tech; Financial Interests, Personal, Ownership Interest, spouse: Ideal Implant; Financial Interests, Personal, Royalties, author medical book: McGraw; Financial Interests, Personal, Royalties: Elsevier; Financial Interests, Personal, Royalties: Springer; Financial Interests, Personal, Royalties: Sage; Financial Interests, Personal, Royalties: Wolters Kluwer; Financial Interests, Personal, Royalties: Wiley; Financial Interests, Institutional, Invited Speaker: Ambrx; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Arvinas; Financial Interests, Institutional, Invited Speaker: Bayer; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: Genentech/Roche; Financial Interests, Institutional, Invited Speaker: Gilead; Financial Interests, Institutional, Invited Speaker: GSK; Financial Interests, Institutional, Invited Speaker: Immunomedics; Financial Interests, Institutional, Invited Speaker: Lilly; Financial Interests, Institutional, Invited Speaker: Macrogenics; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: OBI Pharma; Financial Interests, Institutional, Invited Speaker: Pieris; Financial Interests, Institutional, Invited Speaker: Puma; Financial Interests, Institutional, Invited Speaker: Radius; Financial Interests, Institutional, Invited Speaker: sanofi; Financial Interests, Institutional, Invited Speaker: Seattle Genetics; Financial Interests, Institutional, Invited Speaker: Dignitana; Financial Interests, Institutional, Invited Speaker: Zymeworks; Financial Interests, Institutional, Invited Speaker: Phoenix Molecular Designs, Ltd.; Financial Interests, Institutional, Research Grant: Samumed; Financial Interests, Institutional, Research Grant: Ambrx; Non-Financial Interests, Advisory Role: Daiichi Sankyo; Non-Financial Interests, Principal Investigator: Daiichi Sankyo; Non-Financial Interests, Advisory Role: Novartis; Non-Financial Interests, Principal Investigator: Genentech; Non-Financial Interests, Principal Investigator: Seattle Genetics; Non-Financial Interests, Advisory Role: Ambrx; Non-Financial Interests, Advisory Role: 4DPharma; Non-Financial Interests, Advisory Role: Dantari; Non-Financial Interests, Advisory Role: Macrogenics; Non-Financial Interests, Advisory Role: Lilly; Non-Financial Interests, Advisory Role: Artios; Non-Financial Interests, Advisory Role: Roche; Non-Financial Interests, Advisory Role: Pyxis; Non-Financial Interests, Advisory Role: Amgen; Non-Financial Interests, Advisory Role: Pieris; Non-Financial Interests, Advisory Role: Arvinas; Non-Financial Interests, Advisory Role: Immunomedics/Gilead; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Member: AACR; Non-Financial Interests, Other, speaker: National Breast Cancer Coalition; Non-Financial Interests, Member, site representative for breast cancer guidelines: National Comprehensive Cancer Network. A. Bardia: Financial Interests, Institutional, Financial Interests, grants: Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health/Menarini, Immunomedics/Gilead, Daiichi Pharma/AstraZeneca, Eli Lilly; Financial Interests, Personal, Financial Interests, consulting fees: Pfizer, Novartis, Genentech, Merck, Radius Health/Menarini, Immunomedics/Gilead, Sanofi, Daiichi Pharma/AstraZeneca, Phillips, Eli Lilly, Foundation Medicine. K. Punie: Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Advisory Board: Roche; Financial Interests, Institutional, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Advisory Board: Vifor Pharma; Financial Interests, Institutional, Advisory Board: Eli Lilly; Financial Interests, Institutional, Invited Speaker: Eli Lilly; Financial Interests, Institutional, Invited Speaker: Mundi Pharma; Financial Interests, Institutional, Advisory Board: Pierre Fabre; Financial Interests, Institutional, Advisory Board: McCann Health; Financial Interests, Institutional, Advisory Board: Roularta; Financial Interests, Institutional, Advisory Board: Teva; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Advisory Board: Gilead Sciences; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Other, Consultancy: Roche; Financial Interests, Institutional, Funding: Sanofi; Non-Financial Interests, Principal Investigator: EORTC 1745-ETF-BCG trial; Non-Financial Interests, Other, Committee member: ESMO Young Oncologists Committee; Non-Financial Interests, Invited Speaker: BSMO; Non-Financial Interests, Other, Committee Member: ESMO Resilience Task Force; Non-Financial Interests, Advisory Role: Commission personalized medecine Federal Government Belgium. K. Kalinsky: Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Immunomedics; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Advisory Board: Cyclacel; Financial Interests, Personal, Advisory Board: Oncosec; Financial Interests, Personal, Advisory Board: 4D Pharma; Financial Interests, Personal, Advisory Board: Puma; Financial Interests, Personal, Stocks/Shares, Employment + Stock = spouse: Grail; Financial Interests, Institutional, Invited Speaker: Incyte; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Invited Speaker: Genentech; Financial Interests, Institutional, Invited Speaker: Eli Lilly; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: Calithera; Financial Interests, Institutional, Invited Speaker: Immunomedics; Financial Interests, Institutional, Invited Speaker: Acetylon; Financial Interests, Institutional, Invited Speaker: Seattle Genetics; Financial Interests, Institutional, Invited Speaker: Amgen; Financial Interests, Institutional, Invited Speaker: Zentalis; Financial Interests, Institutional, Invited Speaker: CytomX Therapeutics; Other, Support for attending meetings and/or travel: Eli Lilly; Other, Support for attending meetings and/or travel: AstraZeneca; Other, Support for attending meetings and/or travel: Pfizer; Other, Steering Committee: Immunomedics; Other, Steering Committee: AstraZeneca; Other, Steering Committee: Ambryx; Other, Steering Committee: Genentech. J. Cortés: Financial Interests, Personal, Financial Interests, stock: Leuko, MedSIR, Nektar; Financial Interests, Personal, Financial Interests, honoraria: Novartis, Eisai, Celgene, Pfizer, Roche, Samsung, Lilly, Merck Sharp & Dohme, Daachi Sankyo; Financial Interests, Personal, Financial Interests, consulting or advisory role: Celgene, Cellestia Biotech, AstraZeneca, Roche, Seattle Genetics, Daachi Sankyo, ERYTECH Pharma, Polyphor, Athenex, Lilly, Servier, Merck Sharp & Dohme, GlaxoSmithKline, Leuko, Clovis Oncology, Bioasis, Boehringer, Ingelheim, Ellipses Pharma, HiberCell; Financial Interests, Institutional, Financial Interests, research funding: Ariad, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer, Eisai Farmaceutica, Guardaanth Health, Merck Sharp & Dohme, Pfizer, Puma Co, Queen Mary University of London, Roche, Piqur; Financial Interests, Personal, Financial Interests, travel, accomodations, expenses: Roche, Pfizer, Eisai, Novartis, Daiichi Sankyo. J. O'Shaughnessy: Financial Interests, Personal, Advisory Board: AbbVie; Financial Interests, Personal, Advisory Board: Agendia; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Aptitude Health; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: G1 Therapeutics; Financial Interests, Personal, Advisory Board: Genentech; Financial Interests, Personal, Advisory Board: Immunomedics; Financial Interests, Personal, Advisory Board: Ipsen Biopharmaceuticals; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Myriad; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Ondonate; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Puma; Financial Interests, Personal, Advisory Board: prIME Oncology; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Advisory Board: Syndax. H.S. Rugo: Financial Interests, Personal, Invited Speaker: Puma; Financial Interests, Personal, Advisory Board: samsung; Financial Interests, Personal, Invited Speaker: mylan; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Invited Speaker: Lilly; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: OBI Pharma; Financial Interests, Institutional, Invited Speaker: Immunomedics; Financial Interests, Institutional, Invited Speaker: Macrogenics; Financial Interests, Institutional, Invited Speaker: Daiichi; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker: Merck; Financial Interests, Institutional, Invited Speaker: Odonate; Financial Interests, Institutional, Invited Speaker: sermonix; Financial Interests, Institutional, Invited Speaker: seattle genetics; Financial Interests, Institutional, Invited Speaker: polyphor; Financial Interests, Institutional, Invited Speaker: Boehringer Ingelheim; Non-Financial Interests, Advisory Role, I advise a number of companies without compensation: various. O.K. Yoon: Financial Interests, Personal, Financial Interests, employee, stock options: Gilead. Y. Pan: Financial Interests, Personal, Financial Interests, employee: Gilead. R.J. Delaney: Financial Interests, Personal, Financial Interests, employee, stock or stock options: Gilead. S. Hofsess: Financial Interests, Personal, Financial Interests, employee, meeting attendance, stock options: Gilead; Non-Financial Interests, Personal, Non-Financial Interests, unpaid: Chair of the William Paterson University Professional Science Master’s External Advisory Board. P. Hodgkins: Financial Interests, Personal, Financial Interests, employee, stock options: Gilead Sciences. S. Phan: Financial Interests, Personal, Financial Interests, employee, grants or contracts, meeting attendance, stock or stock options, receipt of materials: Gilead. V. Dieras: Financial Interests, Personal, Financial Interests, consulting fees: Roche Genentech, Novartis, Pfizer, Lilly, AbbVie, Eisai, AstraZeneca, Daiichi Sankyo, Seagen, Gilead, MSD, Pierre Fabre Oncologie; Financial Interests, Personal, Financial Interests, honoraria: Novartis, Pfizer, Lilly, AstraZeneca, Seagen, Daiichi Sankyo, Gilead, MSD; Financial Interests, Personal, Financial Interests, meeting attendance and/or travel: Roche, Novartis, Pfizer, Seagen, Lilly, AstraZeneca, Daiichi Sankyo, Gilead; Financial Interests, Personal, Financial Interests, data safety monitoring board or advisory board: Roche Genentech, Novartis, Pfizer, Lilly, AbbVie, Eisai, AstraZeneca, Daiichi Sankyo, Seagen, Gilead, MSD, Pierre Fabre Oncologie. All other authors have declared no conflicts of interest.

Background

Palbociclib (PB), the first clinically available oral CDK4/6 inhibitor, in combination with endocrine therapy has become standard of care for HR+/HER2– advanced/metastatic breast cancer (MBC). This study compared overall survival (OS) of MBC patients treated with first-line PB+AI vs AI alone in US routine clinical practices.

Methods

We conducted a retrospective analysis of HR+/HER2– MBC patients in the Flatiron Health longitudinal database, representing more than 2.4 million actively treated cancer patients in the US. Between February 2015 and March 2020, 2888 postmenopausal MBC women and men aged ≥18 years started first-line PB+AI or AI therapy. Patients were evaluated from start of PB+AI or AI to September 2020, death, or last visit, whichever came first. Both stabilized inverse probability treatment weighting (sIPTW) and propensity score matching (PSM) statistical methods were used to balance patient characteristics.

Results

Of the eligible patients (1324 with PB+AI and 1564 with AI), median age was 70.0 years, 67.8% were white, 34.8% had de novo MBC, 29.4% had lung or liver involvement, 38.7% had bone-only disease. Median OS in PB+AI vs AI was 53.4 (95%CI=48.7-58.6) vs 40.4 (95%CI=36.3-44.9) months (mo) (HR=0.67, 95%CI=0.60-0.76, p<.0001), respectively. After sIPTW, median OS was 49.1 mo (95%CI=45.2-57.7) for PB+AI vs 43.2 mo (95%CI=37.6-48.0) for AI (HR=0.76, 95%CI=0.65-0.87, p<.0001). After 1:1 PSM, median OS was 57.8 mo (95%CI=47.2—NR) with matched PB+AI vs 43.5 mo (95%CI=37.6-48.9) with matched AI (HR=0.72, 95%CI=0.62-0.83, p<.0001). Table presents key patient characteristics and OS results.

Conclusions

This largest to date real-world comparative effectiveness study demonstrated that palbociclib +AI was significantly associated with prolonged overall survival vs AI alone, supporting first-line palbociclib plus AI as a standard of care for HR+/HER2– MBC patients. Table: 169P

Legal entity responsible for the study

Pfizer Inc.

Funding

Pfizer Inc.

Disclosure

H.S. Rugo: Financial Interests, Institutional, Financial Interests: Pfizer Inc.; Financial Interests, Institutional, Financial Interests: Merck; Financial Interests, Institutional, Financial Interests: Novartis; Financial Interests, Institutional, Financial Interests: Eli Lilly; Financial Interests, Institutional, Financial Interests: Roche; Financial Interests, Institutional, Financial Interests: Daiichi Sankyo; Financial Interests, Institutional, Financial Interests: Seattle Genetics; Financial Interests, Institutional, Financial Interests: Macrogenics; Financial Interests, Institutional, Financial Interests: Sermonix; Financial Interests, Institutional, Financial Interests: Boehringer Ingelheim; Financial Interests, Institutional, Financial Interests: Polyphor; Financial Interests, Institutional, Financial Interests: AstraZeneca; Financial Interests, Institutional, Financial Interests: Ayala; Financial Interests, Institutional, Financial Interests: Gilead; Financial Interests, Institutional, Financial Interests: Puma; Financial Interests, Institutional, Financial Interests: Samsung; Financial Interests, Institutional, Financial Interests: Mylan. A. Brufsky, X. Liu, B. Li, L. McRoy, C. Chen: Financial Interests, Institutional, Financial Interests: Pfizer Inc. R.M. Layman: Financial Interests, Institutional, Financial Interests: Pfizer Inc.; Financial Interests, Institutional, Financial Interests: Novartis; Financial Interests, Institutional, Financial Interests: Eli Lilly; Financial Interests, Institutional, Financial Interests: GlaxoSmithKline; Financial Interests, Institutional, Financial Interests: Zentalis. M. Cristofanilli: Financial Interests, Institutional, Financial Interests: Merck; Financial Interests, Institutional, Financial Interests: AstraZeneca; Financial Interests, Institutional, Financial Interests: Pfizer Inc.; Financial Interests, Institutional, Financial Interests: Menarini; Financial Interests, Institutional, Financial Interests: Eli Lilly; Financial Interests, Institutional, Financial Interests: G1 Therapeutics; Financial Interests, Institutional, Financial Interests: Novartis; Financial Interests, Institutional, Financial Interests: Sermonix; Financial Interests, Institutional, Financial Interests: Foundation Medicine. M.A. Torres: Financial Interests, Institutional, Financial Interests: Pfizer Inc.; Financial Interests, Institutional, Financial Interests: Genentech; Financial Interests, Institutional, Financial Interests: Centers for Disease Control; Financial Interests, Institutional, Financial Interests: Oncohealth; Financial Interests, Institutional, Financial Interests: MJH Life Sciences. G. Curigliano: Financial Interests, Institutional, Financial Interests: Seagen; Financial Interests, Institutional, Financial Interests: Roche; Financial Interests, Institutional, Financial Interests: Novartis; Financial Interests, Institutional, Financial Interests: Lilly; Financial Interests, Institutional, Financial Interests: Daiichi Sankyo; Financial Interests, Institutional, Financial Interests: AstraZeneca; Financial Interests, Institutional, Financial Interests: Pfizer; Financial Interests, Institutional, Financial Interests: Sanofi; Financial Interests, Institutional, Financial Interests: Pierre Fabre; Financial Interests, Institutional, Financial Interests: Gilead. R.S. Finn: Financial Interests, Institutional, Financial Interests: Pfizer Inc.; Financial Interests, Institutional, Financial Interests: Eli Lilly; Financial Interests, Institutional, Financial Interests: Novartis. A. Demichele: Financial Interests, Institutional, Financial Interests: Pfizer Inc.; Financial Interests, Institutional, Financial Interests: Novartis; Financial Interests, Institutional, Financial Interests: Calithera; Financial Interests, Institutional, Financial Interests: Genentech.

Background

The phase 2, noncomparative BYLieve study showed efficacy of ALP (PI3K-α inhibitor and degrader) + ET in pts with PIK3CA-mutated, HR+, HER2– ABC progressing on/after (Cohort A) cyclin-dependent kinase 4/6 inhibitor (CDKi) + aromatase inhibitor (AI), (Cohort B) CDKi + fulvestrant (FUL), or (Cohort C) AI followed by chemotherapy or ET as immediate prior treatment (Tx). Here we report efficacy for subgroups of interest.

Methods

Pts received ALP + FUL (Cohorts A and C) or ALP + letrozole (Cohort B). Subgroups were pre- (PreM) or postmenopausal (PM; includes surgically sterile) status, and presence of bone lesion-only (BO) or visceral disease (VD) regardless of PreM/PM status for each cohort, and prior Tx for Cohort C (prior CDKi + FUL or AI; used only once in any line/setting). Efficacy endpoints assessed in pts with centrally confirmed PIK3CA mutation were progression-free survival (PFS) and overall survival (OS) for Cohort A (18-mo follow-up [FU]) and PFS for Cohorts B and C (6-mo FU).

Results

A total of 16.5%, 5.2%, and 13.9% of pts were PreM in Cohorts A, B, and C, respectively; 18.2% and 67.8%, 9.6% and 76.5%, and 12.2% and 73.9% had BO and VD in Cohorts A, B, and C, respectively. 19.1% and 40.0% of Cohort C pts had prior CDKI + FUL or CDKi + AI Tx, respectively. Median (m) PFS was numerically higher for PM vs PreM pts, pts with vs without BO, and pts without vs with VD (Cohorts A and B). In Cohort C, mPFS was overall similar across subgroups. In Cohort A, mOS was 5.5-mo longer in PM vs PreM pts; Cohorts B and C OS data were immature by cutoff. Efficacy data are summarized in the table. Table: 175P

Conclusions

Overall, these ad hoc exploratory analyses demonstrate clinical benefit of ALP + ET across subgroups of interest (despite low number of pts in some subgroups) in all cohorts, including PreM pts, and pts with VD who typically have worse prognosis.

Clinical trial identification

NCT03056755; EUDRACT2016-004586-67.

Editorial acknowledgement

We thank Marcelene Yumul, MD, and Casandra M. Monzon, PhD, of Healthcare Consultancy Group, LLC, for their medical editorial assistance with this abstract, which was funded by Novartis.

Legal entity responsible for the study

Novartis Pharmaceuticals Corporation.

Funding

Novartis Pharmaceuticals Corporation.

Disclosure

F. Cardoso: Financial Interests, Personal, Other, Consultancy: Amgen; Financial Interests, Personal, Other, Consultancy: Astellas/Medivation; Financial Interests, Personal, Other, Consultancy: AstraZeneca; Financial Interests, Personal, Other, Consultancy: Celgene; Financial Interests, Personal, Other, Consultancy: Daiichi Sankyo; Financial Interests, Personal, Other, Consultancy: Eisai; Financial Interests, Personal, Other, Consultancy: GE Oncology; Financial Interests, Personal, Other, Consultancy: Genentech; Financial Interests, Personal, Other, Consultancy: GlaxoSmithKline; Financial Interests, Personal, Other, Consultancy: Macrogenics; Financial Interests, Personal, Other, Consultancy: Medscape; Financial Interests, Personal, Other, Consultancy: Merck-Sharp; Financial Interests, Personal, Other, Consultancy: Merus BV; Financial Interests, Personal, Other, Consultancy: Mylan; Financial Interests, Personal, Other, Consultancy: Mundipharma; Financial Interests, Personal, Other, Consultancy: Novartis; Financial Interests, Personal, Other, Consultancy: Pfizer; Financial Interests, Personal, Other, Consultancy: Pierre Fabre; Financial Interests, Personal, Other, Consultancy: prIME Oncology; Financial Interests, Personal, Other, Consultancy: Roche; Financial Interests, Personal, Other, Consultancy: Sanofi; Financial Interests, Personal, Other, Consultancy: Samsung Bioepis; Financial Interests, Personal, Other, Consultancy: Seagen; Financial Interests, Personal, Other, Consultancy: Teva; Financial Interests, Institutional, Invited Speaker: Amgen; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Boehringer-Ingelheim; Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker: Bayer; Financial Interests, Institutional, Invited Speaker: Daiichi; Financial Interests, Institutional, Invited Speaker: Eisai; Financial Interests, Institutional, Invited Speaker: Fresenius GmbH; Financial Interests, Institutional, Invited Speaker: Genentech; Financial Interests, Institutional, Invited Speaker: GlaxoSmithKline; Financial Interests, Institutional, Invited Speaker: Ipsen; Financial Interests, Institutional, Invited Speaker: Incyte; Financial Interests, Institutional, Invited Speaker: Nektar Therapeutics; Financial Interests, Institutional, Invited Speaker: Nerviano; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Invited Speaker: Macrogenics; Financial Interests, Institutional, Invited Speaker: Medigene; Financial Interests, Institutional, Invited Speaker: MedImmune; Financial Interests, Institutional, Invited Speaker: Merck; Financial Interests, Institutional, Invited Speaker: Millenium; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: Pierre Fabre; Financial Interests, Institutional, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker: Sanofi-Aventis; Financial Interests, Institutional, Invited Speaker: Sonus; Financial Interests, Institutional, Invited Speaker: Taiho Oncology; Financial Interests, Institutional, Invited Speaker: Tesaro; Financial Interests, Institutional, Invited Speaker: Tigris; Financial Interests, Institutional, Invited Speaker: Wilex; Financial Interests, Institutional, Invited Speaker: Wyeth; Non-Financial Interests, Leadership Role, President: ABC Global Alliance and ABC Consensus Conference and Guidelines; Non-Financial Interests, Member: ESMO; Non-Financial Interests, Member: ESO; Non-Financial Interests, Member: EORTC; Non-Financial Interests, Member: BCG; Non-Financial Interests, Member: IBCSG; Non-Financial Interests, Member: SOLTI; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Member: AACR; Non-Financial Interests, Member: EACR; Non-Financial Interests, Member: SIS; Non-Financial Interests, Member: ASPIC. D. Juric: Financial Interests, Personal, Other, Consulting fees: Novartis, EMD Serono, Eisai, Genentech, Ipsen, Syros Pharmaceuticals, Vibliome Therapeutics, Mapkure, Petra Pharma, Relay Therapeutics; Silverback Therapeutics, PIC Therapeutics; Financial Interests, Institutional, Other, Research funding: Novartis, Genentech, Takeda, Eisai, EMD Serono, Placon, Amgen, Syros Pharmaceuticals, InventisBio, Infinity Pharmaceuticals, Takeda, Pfizer; Financial Interests, Personal, Other, Ownership interest: Relay Therapeutics, PIC Therapeutics, Vibliome Therapeutics. F. Lerebours: Financial Interests, Personal, Other, Support for attending meetings and travel: Eisai, Mundipharma, Novartis, Pfizer, Roche; Financial Interests, Personal, Other, Participation on a Data Safety Monitoring Board or Advisory Board/Honoraria: AstraZeneca/Daiichi Sankyo, Eisai, Lilly, Novartis, Pierre Fabre, Pfizer, Roche, Seagen. I. Krop: Financial Interests, Personal, Other, Support for the present publication: Novartis; Financial Interests, Personal, Other, Payment or honoraria for lectures: Novartis, AstraZeneca, Context Therapeutics, Daiichi Sankyo, Genentech/Roche; Macrogenics, Merck, Seagen; Financial Interests, Institutional, Other, Grants: Genentech/Roche, Macrogenics, Pfizer. M. Ruiz Borrego: Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: AstraZeneca. P. Neven: Financial Interests, Institutional, Other, Consulting or advisory role: Eli Lilly, Gilead, Novartis, Pfizer, Roche, AstraZeneca; Financial Interests, Institutional, Other, Travel, accommodations, expenses: Amgen, AstraZeneca, Eisai, Eli Lilly, Mylan, Novartis, Pierre Fabre, Pfizer, Roche; Financial Interests, Institutional, Research funding non-profit organization: Kom op Tegen Kanker, Think Pink. Y.H. Park: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Other, Research Grant: AstraZeneca; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Institutional, Other, Research Grant: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Institutional, Other, Research Grant: Roche; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Institutional, Other, Research Grant: MSD; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Non-Financial Interests, Principal Investigator: AstraZeneca; Non-Financial Interests, Principal Investigator: Pfizer; Non-Financial Interests, Principal Investigator: Novartis; Non-Financial Interests, Principal Investigator: MSD; Non-Financial Interests, Principal Investigator: Lilly; Non-Financial Interests, Principal Investigator: Roche; Non-Financial Interests, Principal Investigator: Daiichi Sankyo. D. Yardley: Financial Interests, Institutional, Other, Research funding: AbbVie, Amgen, Biomarin, Biothera Pharmaceuticals, Clovis Pharma, Dana Farber Cancer Institute, Lilly, Roche/Genentech, Inycte, Innocrin Pharmaceuticals, MacroGenics, MedImmune, Medivation, Merck, Merrimack Pharmaceuticals, Nektar Therapeutics, Novartis, NSABP, Pfizer, Tesaro, Polyphor; Financial Interests, Institutional, Other, Consulting/Advisory role: Athenex, bioTheranostics, G1 Therapeutics, Immunomedics, Lilly, Merck, Novartis, Pfizer, Sanofi-Aventis. K. Jhaveri: Financial Interests, Personal, Other, Consulting/Advisory role fees: AbbVie, AstraZeneca, Blueprint Medicines, Biotheranostics, BMS, Genentech, Jounce Therapeutics, Lilly Pharmaceuticals, Novartis, Pfizer, Seattle Genetics, SunPharma Pvt Ltd, Taiho Oncology; Financial Interests, Institutional, Other, Research funding: ADC Therapeutics, AstraZeneca, Clovis Oncology, Debio Pharmaceuticals, Genentech, Immunomedics, Novartis, Lilly Pharmaceuticals, Merck/VelosBio, Novartis, Novita Pharmaceuticals, Pfizer, Puma Biotechnology, Zymeworks. C. Arce, M. Akdere: Financial Interests, Personal, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks/Shares: Novartis. E. Gu: Financial Interests, Personal, Full or part-time Employment: Novartis; Financial Interests, Personal, Other, Travel: Novartis. H.S. Rugo: Financial Interests, Personal, Invited Speaker: Puma; Financial Interests, Personal, Advisory Board: samsung; Financial Interests, Personal, Invited Speaker: mylan; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Invited Speaker: Lilly; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: OBI Pharma; Financial Interests, Institutional, Invited Speaker: Immunomedics; Financial Interests, Institutional, Invited Speaker: Macrogenics; Financial Interests, Institutional, Invited Speaker: Daiichi; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker: Merck; Financial Interests, Institutional, Invited Speaker: Odonate; Financial Interests, Institutional, Invited Speaker: sermonix; Financial Interests, Institutional, Invited Speaker: Seattle Genetics; Financial Interests, Institutional, Invited Speaker: polyphor; Financial Interests, Institutional, Invited Speaker: Boehringer Ingelheim; Non-Financial Interests, Advisory Role, I advise a number of companies without compensation: various.

Background

Gaps in RW evidence exist regarding pts’ and health-care professionals’ (HCPs) perspectives on SEs impacting QOL. Previously, RW survey results showed disconnects between pts with ABC and HCPs on the importance of QOL discussions (Cardoso, SABCS 2021). Here, we examine how SEs impacting QOL in pts with ABC are perceived.

Methods

The survey was designed by a committee of oncologists, nurses, advocates, and pts. After ethical approval, data were collected from July 2020 to May 2021 via a cross-sectional online survey of oncologists, nurses, and pts with HR+/HER2− ABC in 7 countries. HCPs and pts were surveyed on the impact of SEs on QOL and HCP interactions. Observations were assessed using a 4-point Likert scale.

Results

The survey was completed by 467 pts and 502 HCPs. Most pts and HCPs believed fear of progression (76% & 92%, respectively) and pain (73% & 96%) had a moderate/severe impact on QOL. The most common SEs experienced by pts since starting ABC tx or their current tx were fatigue (73% & 64%) and pain (64% & 42% [back pain]). Fatigue relieved by rest was believed to have a moderate/severe impact on QOL more so by pts (78%) than HCPs (40%). Most pts did not discuss SEs with HCPs (79% for fatigue, 74% for pain) until these were moderate/severe. Pts reported that insomnia (83%), anxiety (82%), back pain (78%), fatigue (77%), and diarrhea (71%) had a moderate/severe impact on their QOL. Pts were least willing to live with back pain (52%), fatigue (42%), diarrhea (41%), and loss of appetite (41%) even if tx was working. In pts on a CDK4/6i, 83% experienced ≥ 1 moderate/severe SE, with insomnia (85%), diarrhea (75%), back pain (75%), and fatigue (74%) having a moderate/severe impact on QOL.

Conclusions

Pts with ABC and HCPs were generally aligned on SEs that severely impacted QOL, but HCPs may undervalue the impact of mild SEs on pts. Fatigue and pain were the most common SEs experienced by pts. In pts on a CDK4/6i, insomnia, diarrhea, back pain, and fatigue had a moderate/severe impact on QOL. These data support close monitoring, early intervention, and when indicated, prophylaxis of SEs that may greatly impact QOL in pts with ABC.

Editorial acknowledgement

Medical writing support was provided by Shashank Tandon at MediTech Media, funded by Novartis Pharmaceuticals Corporation.

Legal entity responsible for the study

Novartis Pharmaceuticals Corporation.

Funding

Novartis Pharmaceuticals Corporation.

Disclosure

F. Cardoso: Financial Interests, Personal, Other: Amgen; Financial Interests, Personal, Other: Astellas/Medivation; Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal, Other: Celgene; Financial Interests, Personal, Other: Daiichi Sankyo; Financial Interests, Personal, Other: EISAI; Financial Interests, Personal, Other: GE Oncology; Financial Interests, Personal, Other: Genentech; Financial Interests, Personal, Other: GSK; Financial Interests, Personal, Other: Macrogenics; Financial Interests, Personal, Other: Medscape; Financial Interests, Personal, Other: Merck-Sharp; Financial Interests, Personal, Other: Merus; Financial Interests, Personal, Other: Mylan; Financial Interests, Personal, Other: Mundipharma; Financial Interests, Personal, Other: Novartis; Financial Interests, Personal, Other: Pfizer; Financial Interests, Personal, Other: Pierre Fabre; Financial Interests, Personal, Other: prIME Oncology; Financial Interests, Personal, Other: Roche; Financial Interests, Personal, Other: Sanofi; Financial Interests, Personal, Other: Samsung Bioepis; Financial Interests, Personal, Other: Teva; Financial Interests, Personal, Other: Seagen; Financial Interests, Personal, Other: Debiopharm; Financial Interests, Personal, Other: Gilead; Financial Interests, Personal, Other: Iqvia; Financial Interests, Personal, Other: Touchime; Other, Personal, Writing Engagements, Medical Writer Support: Novartis. J. Rihani: Financial Interests, Personal, Invited Speaker, For participating in various Novartis (sponsored) events, i.e. giving talks, a member in committees and on patient engagement panels: Novartis. D. Aubel: Financial Interests, Personal, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks/Shares: Novartis. J. de Courcy: Financial Interests, Institutional, Other, Adelphi Real World received payment from Novartis to conduct the study: Novartis; Financial Interests, Institutional, Other, Adelphi Real World received payment from Novartis to conduct the study: Adelphi Real World. N. Harbeck: Financial Interests, Personal, Other, Consulting: Novartis; Financial Interests, Personal, Invited Speaker, Lectures: Novartis; Financial Interests, Personal, Invited Speaker, Lectures: Lilly; Financial Interests, Personal, Other, Consulting: Lilly; Financial Interests, Personal, Invited Speaker, Lectures: AstraZeneca; Financial Interests, Personal, Other, Consulting: AstraZeneca; Financial Interests, Personal, Invited Speaker, Lectures: Daiichi Sankyo; Financial Interests, Personal, Other, Consulting: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker, Lectures: MSD; Financial Interests, Personal, Other, Consulting: MSD; Financial Interests, Personal, Invited Speaker, Lectures: Pierre Fabre; Financial Interests, Personal, Other, Consulting: Pierre Fabre; Financial Interests, Personal, Invited Speaker, Lectures: Roche; Financial Interests, Personal, Other, Consulting: Roche; Financial Interests, Personal, Invited Speaker, Lectures: Sandoz/Hexal; Financial Interests, Personal, Other, Consulting: Sandoz/Hexal; Financial Interests, Personal, Invited Speaker, Lectures: Seattle Genetics; Financial Interests, Personal, Other, Consulting: Seattle Genetics; Non-Financial Interests, Personal, Member of the Board of Directors, Co-Director WSG: West German Study Group. H.S. Rugo: Financial Interests, Institutional, Research Grant, Grant - Institution: Plexxikon; Financial Interests, Institutional, Research Grant, Grant - Institution: Macrogenics; Financial Interests, Institutional, Research Grant, Grant - Institution: OBI Pharma; Financial Interests, Institutional, Research Grant, Grant - Institution: Eisai; Financial Interests, Institutional, Research Grant, Grant - Institution: Pfizer; Financial Interests, Institutional, Research Grant, Grant - Institution: Novartis; Financial Interests, Institutional, Research Grant, Grant - Institution: Eli Lilly; Financial Interests, Institutional, Research Grant, Grant - Institution: GlaxoSmithKline; Financial Interests, Institutional, Research Grant, Grant - Institution: Genentech; Financial Interests, Institutional, Research Grant, Grant - Institution: Celsion; Financial Interests, Institutional, Research Grant, Grant - Institution: Merck; Financial Interests, Personal, Other, Travel, Accomodations, and Expenses: Novartis; Financial Interests, Personal, Other, Travel, Accomodations, and Expenses: Roche/Genentech; Financial Interests, Personal, Other, Travel, Accomodations, and Expenses: OBI Pharma; Financial Interests, Personal, Other, Travel, Accomodations, and Expenses: Bayer; Financial Interests, Personal, Other, Travel, Accomodations, and Expenses: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Genomic Health. P.A. Fasching: Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Institutional, Funding, Institutional Funding: BioNTech; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Invited Speaker: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Institutional, Funding, Institutional Funding: Cepheid; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Seagen; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Hexal; Financial Interests, Personal, Advisory Board: Agendia; Financial Interests, Personal, Advisory Board: Sanofi Aventis; Financial Interests, Personal, Invited Speaker: Gilead; Financial Interests, Personal, Advisory Board: Gilead.

S. Haftchenary: Financial Interests, Personal, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks/Shares, Stock ownership: Novartis. P. Pathak: Financial Interests, Personal, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks/Shares, Stock ownership: Novartis. All other authors have declared no conflicts of interest.

Background

²²³Ra extends overall survival (OS) in pts with bone-metastatic castration-resistant prostate cancer. This study evaluated if the addition of ²²³Ra to EXE-EVE provided increased benefit over EXE-EVE in pts with bone dominant HR+/HER2- MBC.

Methods

This was a multinational, double-blind, placebo-controlled phase II study (NCT02258451). Pts with bone dominant HR+/HER2- MBC received EXE-EVE and were randomized 1:1 to ²²³Ra or placebo (Pbo). The primary end point (EP) was symptomatic skeletal event-free survival (SSE-FS). 160 events gave 90% power to detect a 50% increase in SSE-FS with a 1-sided alpha of 0.10 (2-sided: 0.20). Secondary EPs included OS, radiographic progression-free survival (rPFS), and safety. Exploratory EPs included time to bone-alkaline phosphatase (B-ALP) progression.

Results

142 pts were assigned to ²²³Ra and 141 to Pbo. Accrual was stopped after an unblinded interim analysis of efficacy as authorized by protocol amendment. Due to lack of promising efficacy and poor enrollment the study was closed. There were 149 SSE-FS events. SSE-FS was 21.1 months (m) for ²²³Ra versus (vs) 19.9 m for Pbo (hazard ratio [HR] 0.891, 95% confidence interval [CI] 0.643–1.233, p=0.4843). OS was 25.0 m vs 26.4 m for ²²³Ra and Pbo, respectively (HR 0.968, 95% CI 0.697–1.343, p=0.8438). rPFS was 7.9 m vs 6.7 m for ²²³Ra and Pbo, respectively (HR 0.874, 95% CI 0.660–1.157, p=0.3467). Incidence of treatment-emergent adverse events (TEAEs) is shown in the table. Time to B-ALP progression was 6.1 m for ²²³Ra and 4.3 m for Pbo (HR 0.645, 95% CI 0.374–1.114, p=0.1135).

Conclusions

This study closed before full enrollment. Available data demonstrated similar efficacy between the arms. The safety profile of the ²²³Ra and EXE-EVE combination was consistent with the known safety profiles of each drug. Table: 182P

Clinical trial identification

NCT02258451 EudraCT number: 2014-002114-23.

Editorial acknowledgement

Dr Egle McDonald of Cancer Communications and Consultancy Ltd, Plumley, UK, provided editorial assistance in the writing of the abstract.

Legal entity responsible for the study

Bayer.

Funding

Bayer.

Disclosure

H.S. Rugo: Financial Interests, Personal, Invited Speaker: PUMA; Financial Interests, Personal, Advisory Board: samsung; Financial Interests, Personal, Invited Speaker: mylan; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Invited Speaker: Lilly; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: OBI Pharma; Financial Interests, Institutional, Invited Speaker: Immunomedics; Financial Interests, Institutional, Invited Speaker: Macrogenics; Financial Interests, Institutional, Invited Speaker: Daiichi; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker: Merck; Financial Interests, Institutional, Invited Speaker: Odonate; Financial Interests, Institutional, Invited Speaker: sermonix; Financial Interests, Institutional, Invited Speaker: seattle genetics; Financial Interests, Institutional, Invited Speaker: polyphor; Financial Interests, Institutional, Invited Speaker: Boehringer Ingelheim; Non-Financial Interests, Advisory Role, I advise a number of companies without compensation: various. S.C. Lee: Financial Interests, Personal, Research Grant: Pfizer; Financial Interests, Personal, Research Grant: Eisai; Financial Interests, Personal, Research Grant: Taiho; Financial Interests, Personal, Research Grant: Act Genomics; Financial Interests, Personal, Research Grant: Bayer; Financial Interests, Personal, Research Grant: Karyopharm; Financial Interests, Personal, Other, Honorarium for advisory board or speaking engagements: Pfizer; Financial Interests, Personal, Other, Honorarium for advisory board or speaking engagements: Novartis; Financial Interests, Personal, Other, Honorarium for advisory board or speaking engagements: AstraZeneca; Financial Interests, Personal, Other, Honorarium for advisory board or speaking engagements: Act Genomics; Financial Interests, Personal, Other, Honorarium for advisory board or speaking engagements: Eli Lilly; Financial Interests, Personal, Other, Honorarium for advisory board or speaking engagements: MSD; Financial Interests, Personal, Other, Honorarium for advisory board or speaking engagements: Roche; Financial Interests, Personal, Other, Honorarium for advisory board or speaking engagements: Eisai; Financial Interests, Personal, Other, Support for conference: Amgen; Financial Interests, Personal, Other, Support for conference: Pfizer; Financial Interests, Personal, Other, Support for conference: Roche. M. Campone: Financial Interests, Institutional, Other, Consulting/advisory role/fees: AstraZeneca; Financial Interests, Institutional, Other, Consulting/advisory role/fees: Sanofi; Financial Interests, Institutional, Other, Consulting/advisory role/fees: Servier; Financial Interests, Institutional, Other, Consulting/advisory role/fees: AbbVie; Financial Interests, Personal, Other, Consulting/advisory role/honoraria: Lilly; Financial Interests, Institutional, Other, Consulting/advisory role/fees: Accord; Financial Interests, Personal, Other, Consulting/advisory role/Speaker's bureau: Novartis; Financial Interests, Personal, Other, Consulting/advisory role/personnal fee: Pfizer; Financial Interests, Personal, Other, Consulting/advisory role: GT1; Financial Interests, Personal, Other, Consuting/advisory role/personnal fee: Daiichi Sankyo; Financial Interests, Institutional, Other, Consulting/advisory role: GILEAD. C. Van Poznak: Financial Interests, Institutional, Principal Investigator, Research funding: Bayer. J.M. Siegel, R. Li, D. Uema, V.J. Wagner: Financial Interests, Personal, Full or part-time Employment: Bayer. R.E. Coleman: Financial Interests, Personal, Other, Consultancy fees: Amgen; Financial Interests, Personal, Other, Consultancy fees: AstraZeneca; Financial Interests, Personal, Other, Consultancy fees: Boehringer Ingelheim; Financial Interests, Personal, Other, Consultancy fees: ITM; Financial Interests, Personal, Other, Consultancy fees: Menarini; Financial Interests, Personal, Other, Consultancy fees: Sanofi; Financial Interests, Personal, Other, Speaker fees: Amgen; Financial Interests, Personal, Other, Speaker fees: ITM; Financial Interests, Personal, Other, Speaker fees: Novartis; Financial Interests, Personal, Other, Speaker fees: Pierre Fabre; Financial Interests, Personal, Other, Co-inventor and patent holder with share options of a biomarker under development: Inbiomotion. All other authors have declared no conflicts of interest.

Background

One of the most devastating complications of metastatic breast cancer (MBC) is the development leptomeningeal disease (LMD), which has a median overall survival of 2-4 months. In order to develop better diagnostic and therapeutic tools for LMD, it is important to better understand the biology of this condition. The objective of this project is to characterize the cerebrospinal fluid (CSF) immune microenvironment at the proteomic level, with a focus on better understanding the exhaustion state of T cells in patients with MBC and LMD.

Methods

Patients with histologically confirmed MBC with known or suspected LMD who were undergoing CSF sampling per standard of care were eligible to enroll in this non-therapeutic study at the University of California, San Francisco. We used a high-dimensional, multiplexed flow cytometry to profile CSF and peripheral blood mononuclear cell (PMBC) immune cell populations, comparing patients with LMD versus those without.

Results

Twelve patients enrolled in this study, including 7 with LMD (based on positive CSF cytology and/or MRI imaging) and 5 without LMD. Six patients were hormone receptor positive (HR+), human epidermal receptor 2 negative (HER2-) and 6 patients were ER+/HER2+. Most patients were heavily pre-treated (median lines MBC therapy = 3, range 0-12). Comparing the CSF immune profiles, patients with LMD had a lower frequency of total immune cells as well as CD8+ T cells compared to patients without LMD. Using unsupervised clustering to further dissect the immune population, we found the frequency of partially exhausted CD8+ T cells (PD-1^low/int, LAG3^high, TIM3^high, CD38^low) was 2-fold higher while a subset of nonclassical monocytes was lower in patients with LMD compared to those without. There were no significant differences in the PMBC immune profiles between patients with LMD and those without.

Conclusions

This study suggests that there may be unique CSF immune composition among patients with LMD versus those without. Larger studies are needed to validate these findings and determine whether there are prognostic or predictive features of the CSF immune cell profile which may have clinical utility.

Legal entity responsible for the study

The authors.

Funding

UCSF Marcus Award Seeding Bold Ideas.

Disclosure

H.S. Rugo: Financial Interests, Personal, Invited Speaker: Puma, Mylan; Financial Interests, Personal, Advisory Board: Samsung; Financial Interests, Institutional, Invited Speaker: Novartis, Lilly, Pfizer, OBI Pharma, Immunomedics, Macrogenics, Daiichi, AstraZeneca, Roche, Merck, Odonate, Sermonix, Seattle Genetics, Polyphor, Boehringer Ingelheim; Non-Financial Interests, Advisory Role, I advise a number of companies without compensation: Various. M. Krummel: Financial Interests, Personal, Ownership Interest, Founder and shareholder: Pionyr Immunotherapeutics, Foundery Innovations Studio; Financial Interests, Personal, Advisory Board: Deciduous Therapeutics. M. Melisko: Financial Interests, Institutional, Research Grant: Novartis, KCRN Research, Puma, Seattle Genetics, OBI Pharma; Financial Interests, Personal, Invited Speaker, Spouse- speaker bureau/honoraria: Genentech; Financial Interests, Personal, Stocks/Shares, Spouse: Merrimack. All other authors have declared no conflicts of interest.

Background

Targeting the androgen receptor (AR) may be the next important endocrine therapy for advanced breast cancer. Enobosarm is an oral selective AR targeting agonist that activates the AR in breast cancer. Enobosarm has an extensive clinical experience in 25 clinical trials including in 2 phase 2 studies conducted in patients (pts) with AR+ ER+ HER2- metastatic breast cancer (MBC). An open-label, parallel design phase 2 study, was conducted in 136 women with heavily pretreated ER+ HER2- MBC that were randomized to oral daily enobosarm at a dose of 9 or 18 mg. The primary endpoint of clinical benefit rate (CBR) at 24 weeks was 32% (9 mg) and 29% (18 mg). A post-hoc AR expression subset analysis conducted in the ITT population with measurable disease at baseline revealed that the best overall response rate (ORR) was significantly higher in pts with ≥40% AR nuclei staining versus <40%, 34% and 2.7% respectively (p=0.0003) and the CBR at 24 weeks was significantly higher for ≥40% AR versus <40%, 52% and 14% respectively (p<0.0004). Overall, enobosarm was well tolerated with significant positive effects on quality-of-life measurements.

Trial design

The ARTEST trial is an ongoing phase 3 multicenter, international, randomized, and open-label study. Approximately, 210 pts with AR+ ER+ HER2- MBC and with AR nuclei staining ≥40% are being randomized 1:1 to either enobosarm 9 mg oral daily dose or an active comparator (physician’s choice of exemestane ± everolimus or SERM). Pts must have previously received a nonsteroidal AI inhibitor, fulvestrant, and a CDK 4/6 inhibitor for MBC and had a ≥ 6 months response to hormone therapy for MBC. The primary endpoint is imaging based progression free survival as measured by RECIST 1.1. The secondary endpoints on this study include the ORR, duration of response, overall survival, change from baseline in Short Physical Performance Battery (SPPB) and change in EORTC Quality of Life Questionnaire (EORTC-QLQ).

Clinical trial identification

NCT04869943.

Legal entity responsible for the study

Veru Inc.

Funding

Veru Inc.

Disclosure

A. Brufsky: Financial Interests, Personal, Advisory Role: Veru Inc. H. Linden, H.S. Rugo, C. Vogel, J. O'Shaughnessy, E. Mayer: Financial Interests, Institutional, Research Grant: Veru Inc. R.H. Getzenberg, K.G. Barnette, D. Rodriguez, M.S. Steiner: Financial Interests, Personal, Full or part-time Employment: Veru Inc.

Background

HER2-targeted therapies have changed the treatment landscape for pts with HER2-positive (+) breast cancer (BC), but the clinical benefit of these first-generation HER2 targeted agents is just emerging for patients with HER2-low disease. HER2-low, defined as IHC 1-2+ without HER2 gene amplification, comprises between 40-65% of HER2-negative breast cancer. While HER2-positive BC comprises approximately 20% of newly diagnosed cases, a greater proportion of patients (∼50%) have BC categorized as HER2-low (IHC 1-2+ but ISH negative) and have a high unmet medical need. Even with the success of anti-HER2 treatments for HER2+ patients, many patients become resistant or are refractory to treatment. A new generation of anti-HER2 targeted agents has recently demonstrated both clinical activity and safety in HER2-low BC, including ARX788, an anti-HER2 antibody drug conjugate (ADC). ARX788 is a site-specific conjugated ADC that consists of a HER2 targeting monoclonal antibody (mAb) with payload AS269, a highly potent tubulin inhibitor. Site-specificity, high homogeneity, and stable covalent conjugation of ARX788 leads to its slow release and prolonged peak of serum pAF-AS269, which may contribute to the lower systemic toxicity and increased targeted delivery of payload to tumor cells at a lower effective dose compared to other HER2 ADCs.

Trial design

ACE-Pan tumor-01 (NCT03255070) is a global phase 1 study to assess efficacy and safety of ARX788 in patients with metastatic HER2+ BC, HER2-low BC, HER2+ GC (gastric cancer), or other advanced solid tumors with HER2 overexpression or activating mutations (including BC). Eligibily includes non-operable Stage III-IV disease, measurable lesions. HER2+ cohort must be resistant/refractory to T-DM1, and/or T-DXd, and/or tucatinib containing regimens, while HER2 low cohort must have no standard curative/palliative measures. Endpoints: ORR, DOR, TTR, BOR, DCR, PFS, and OS using RECIST1.1. Safety assessed by PE, AEs, VS, ECG, and lab tests PK, immunogenicity, biomarkers to be analyzed. Descriptive statistics will be used. As of Feb/2022, 28 patients with ongoing enrollment.

Clinical trial identification

NCT03255070.

Legal entity responsible for the study

Ambrx, Inc.

Funding

Ambrx, Inc.

Disclosure

D. Xu, M. Li, T. Le: Financial Interests, Personal, Full or part-time Employment: Ambrx. J. Yan: Financial Interests, Personal, Member of the Board of Directors: Ambrx. All other authors have declared no conflicts of interest.

Background

Palbociclib (PB), the first clinically available oral CDK4/6 inhibitor, in combination with endocrine therapy has become standard of care for HR+/HER2– advanced/metastatic breast cancer (MBC). This study compared overall survival (OS) of MBC patients treated with first-line PB+AI vs AI alone in US routine clinical practices.

Methods

We conducted a retrospective analysis of HR+/HER2– MBC patients in the Flatiron Health longitudinal database, representing more than 2.4 million actively treated cancer patients in the US. Between February 2015 and March 2020, 2888 postmenopausal MBC women and men aged ≥18 years started first-line PB+AI or AI therapy. Patients were evaluated from start of PB+AI or AI to September 2020, death, or last visit, whichever came first. Both stabilized inverse probability treatment weighting (sIPTW) and propensity score matching (PSM) statistical methods were used to balance patient characteristics.

Results

Of the eligible patients (1324 with PB+AI and 1564 with AI), median age was 70.0 years, 67.8% were white, 34.8% had de novo MBC, 29.4% had lung or liver involvement, 38.7% had bone-only disease. Median OS in PB+AI vs AI was 53.4 (95%CI=48.7-58.6) vs 40.4 (95%CI=36.3-44.9) months (mo) (HR=0.67, 95%CI=0.60-0.76, p<.0001), respectively. After sIPTW, median OS was 49.1 mo (95%CI=45.2-57.7) for PB+AI vs 43.2 mo (95%CI=37.6-48.0) for AI (HR=0.76, 95%CI=0.65-0.87, p<.0001). After 1:1 PSM, median OS was 57.8 mo (95%CI=47.2—NR) with matched PB+AI vs 43.5 mo (95%CI=37.6-48.9) with matched AI (HR=0.72, 95%CI=0.62-0.83, p<.0001). Table presents key patient characteristics and OS results.

Conclusions

This largest to date real-world comparative effectiveness study demonstrated that palbociclib +AI was significantly associated with prolonged overall survival vs AI alone, supporting first-line palbociclib plus AI as a standard of care for HR+/HER2– MBC patients. Table: 169P

Legal entity responsible for the study

Pfizer Inc.

Funding

Pfizer Inc.

Disclosure

H.S. Rugo: Financial Interests, Institutional, Financial Interests: Pfizer Inc.; Financial Interests, Institutional, Financial Interests: Merck; Financial Interests, Institutional, Financial Interests: Novartis; Financial Interests, Institutional, Financial Interests: Eli Lilly; Financial Interests, Institutional, Financial Interests: Roche; Financial Interests, Institutional, Financial Interests: Daiichi Sankyo; Financial Interests, Institutional, Financial Interests: Seattle Genetics; Financial Interests, Institutional, Financial Interests: Macrogenics; Financial Interests, Institutional, Financial Interests: Sermonix; Financial Interests, Institutional, Financial Interests: Boehringer Ingelheim; Financial Interests, Institutional, Financial Interests: Polyphor; Financial Interests, Institutional, Financial Interests: AstraZeneca; Financial Interests, Institutional, Financial Interests: Ayala; Financial Interests, Institutional, Financial Interests: Gilead; Financial Interests, Institutional, Financial Interests: Puma; Financial Interests, Institutional, Financial Interests: Samsung; Financial Interests, Institutional, Financial Interests: Mylan. A. Brufsky, X. Liu, B. Li, L. McRoy, C. Chen: Financial Interests, Institutional, Financial Interests: Pfizer Inc. R.M. Layman: Financial Interests, Institutional, Financial Interests: Pfizer Inc.; Financial Interests, Institutional, Financial Interests: Novartis; Financial Interests, Institutional, Financial Interests: Eli Lilly; Financial Interests, Institutional, Financial Interests: GlaxoSmithKline; Financial Interests, Institutional, Financial Interests: Zentalis. M. Cristofanilli: Financial Interests, Institutional, Financial Interests: Merck; Financial Interests, Institutional, Financial Interests: AstraZeneca; Financial Interests, Institutional, Financial Interests: Pfizer Inc.; Financial Interests, Institutional, Financial Interests: Menarini; Financial Interests, Institutional, Financial Interests: Eli Lilly; Financial Interests, Institutional, Financial Interests: G1 Therapeutics; Financial Interests, Institutional, Financial Interests: Novartis; Financial Interests, Institutional, Financial Interests: Sermonix; Financial Interests, Institutional, Financial Interests: Foundation Medicine. M.A. Torres: Financial Interests, Institutional, Financial Interests: Pfizer Inc.; Financial Interests, Institutional, Financial Interests: Genentech; Financial Interests, Institutional, Financial Interests: Centers for Disease Control; Financial Interests, Institutional, Financial Interests: Oncohealth; Financial Interests, Institutional, Financial Interests: MJH Life Sciences. G. Curigliano: Financial Interests, Institutional, Financial Interests: Seagen; Financial Interests, Institutional, Financial Interests: Roche; Financial Interests, Institutional, Financial Interests: Novartis; Financial Interests, Institutional, Financial Interests: Lilly; Financial Interests, Institutional, Financial Interests: Daiichi Sankyo; Financial Interests, Institutional, Financial Interests: AstraZeneca; Financial Interests, Institutional, Financial Interests: Pfizer; Financial Interests, Institutional, Financial Interests: Sanofi; Financial Interests, Institutional, Financial Interests: Pierre Fabre; Financial Interests, Institutional, Financial Interests: Gilead. R.S. Finn: Financial Interests, Institutional, Financial Interests: Pfizer Inc.; Financial Interests, Institutional, Financial Interests: Eli Lilly; Financial Interests, Institutional, Financial Interests: Novartis. A. Demichele: Financial Interests, Institutional, Financial Interests: Pfizer Inc.; Financial Interests, Institutional, Financial Interests: Novartis; Financial Interests, Institutional, Financial Interests: Calithera; Financial Interests, Institutional, Financial Interests: Genentech.

Background

²²³Ra extends overall survival (OS) in pts with bone-metastatic castration-resistant prostate cancer. This study evaluated if the addition of ²²³Ra to EXE-EVE provided increased benefit over EXE-EVE in pts with bone dominant HR+/HER2- MBC.

Methods

This was a multinational, double-blind, placebo-controlled phase II study (NCT02258451). Pts with bone dominant HR+/HER2- MBC received EXE-EVE and were randomized 1:1 to ²²³Ra or placebo (Pbo). The primary end point (EP) was symptomatic skeletal event-free survival (SSE-FS). 160 events gave 90% power to detect a 50% increase in SSE-FS with a 1-sided alpha of 0.10 (2-sided: 0.20). Secondary EPs included OS, radiographic progression-free survival (rPFS), and safety. Exploratory EPs included time to bone-alkaline phosphatase (B-ALP) progression.

Results

142 pts were assigned to ²²³Ra and 141 to Pbo. Accrual was stopped after an unblinded interim analysis of efficacy as authorized by protocol amendment. Due to lack of promising efficacy and poor enrollment the study was closed. There were 149 SSE-FS events. SSE-FS was 21.1 months (m) for ²²³Ra versus (vs) 19.9 m for Pbo (hazard ratio [HR] 0.891, 95% confidence interval [CI] 0.643–1.233, p=0.4843). OS was 25.0 m vs 26.4 m for ²²³Ra and Pbo, respectively (HR 0.968, 95% CI 0.697–1.343, p=0.8438). rPFS was 7.9 m vs 6.7 m for ²²³Ra and Pbo, respectively (HR 0.874, 95% CI 0.660–1.157, p=0.3467). Incidence of treatment-emergent adverse events (TEAEs) is shown in the table. Time to B-ALP progression was 6.1 m for ²²³Ra and 4.3 m for Pbo (HR 0.645, 95% CI 0.374–1.114, p=0.1135).

Conclusions

This study closed before full enrollment. Available data demonstrated similar efficacy between the arms. The safety profile of the ²²³Ra and EXE-EVE combination was consistent with the known safety profiles of each drug. Table: 182P

Clinical trial identification

NCT02258451 EudraCT number: 2014-002114-23.

Editorial acknowledgement

Dr Egle McDonald of Cancer Communications and Consultancy Ltd, Plumley, UK, provided editorial assistance in the writing of the abstract.

Legal entity responsible for the study

Bayer.

Funding

Bayer.

Disclosure

H.S. Rugo: Financial Interests, Personal, Invited Speaker: PUMA; Financial Interests, Personal, Advisory Board: samsung; Financial Interests, Personal, Invited Speaker: mylan; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Invited Speaker: Lilly; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: OBI Pharma; Financial Interests, Institutional, Invited Speaker: Immunomedics; Financial Interests, Institutional, Invited Speaker: Macrogenics; Financial Interests, Institutional, Invited Speaker: Daiichi; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker: Merck; Financial Interests, Institutional, Invited Speaker: Odonate; Financial Interests, Institutional, Invited Speaker: sermonix; Financial Interests, Institutional, Invited Speaker: seattle genetics; Financial Interests, Institutional, Invited Speaker: polyphor; Financial Interests, Institutional, Invited Speaker: Boehringer Ingelheim; Non-Financial Interests, Advisory Role, I advise a number of companies without compensation: various. S.C. Lee: Financial Interests, Personal, Research Grant: Pfizer; Financial Interests, Personal, Research Grant: Eisai; Financial Interests, Personal, Research Grant: Taiho; Financial Interests, Personal, Research Grant: Act Genomics; Financial Interests, Personal, Research Grant: Bayer; Financial Interests, Personal, Research Grant: Karyopharm; Financial Interests, Personal, Other, Honorarium for advisory board or speaking engagements: Pfizer; Financial Interests, Personal, Other, Honorarium for advisory board or speaking engagements: Novartis; Financial Interests, Personal, Other, Honorarium for advisory board or speaking engagements: AstraZeneca; Financial Interests, Personal, Other, Honorarium for advisory board or speaking engagements: Act Genomics; Financial Interests, Personal, Other, Honorarium for advisory board or speaking engagements: Eli Lilly; Financial Interests, Personal, Other, Honorarium for advisory board or speaking engagements: MSD; Financial Interests, Personal, Other, Honorarium for advisory board or speaking engagements: Roche; Financial Interests, Personal, Other, Honorarium for advisory board or speaking engagements: Eisai; Financial Interests, Personal, Other, Support for conference: Amgen; Financial Interests, Personal, Other, Support for conference: Pfizer; Financial Interests, Personal, Other, Support for conference: Roche. M. Campone: Financial Interests, Institutional, Other, Consulting/advisory role/fees: AstraZeneca; Financial Interests, Institutional, Other, Consulting/advisory role/fees: Sanofi; Financial Interests, Institutional, Other, Consulting/advisory role/fees: Servier; Financial Interests, Institutional, Other, Consulting/advisory role/fees: AbbVie; Financial Interests, Personal, Other, Consulting/advisory role/honoraria: Lilly; Financial Interests, Institutional, Other, Consulting/advisory role/fees: Accord; Financial Interests, Personal, Other, Consulting/advisory role/Speaker's bureau: Novartis; Financial Interests, Personal, Other, Consulting/advisory role/personnal fee: Pfizer; Financial Interests, Personal, Other, Consulting/advisory role: GT1; Financial Interests, Personal, Other, Consuting/advisory role/personnal fee: Daiichi Sankyo; Financial Interests, Institutional, Other, Consulting/advisory role: GILEAD. C. Van Poznak: Financial Interests, Institutional, Principal Investigator, Research funding: Bayer. J.M. Siegel, R. Li, D. Uema, V.J. Wagner: Financial Interests, Personal, Full or part-time Employment: Bayer. R.E. Coleman: Financial Interests, Personal, Other, Consultancy fees: Amgen; Financial Interests, Personal, Other, Consultancy fees: AstraZeneca; Financial Interests, Personal, Other, Consultancy fees: Boehringer Ingelheim; Financial Interests, Personal, Other, Consultancy fees: ITM; Financial Interests, Personal, Other, Consultancy fees: Menarini; Financial Interests, Personal, Other, Consultancy fees: Sanofi; Financial Interests, Personal, Other, Speaker fees: Amgen; Financial Interests, Personal, Other, Speaker fees: ITM; Financial Interests, Personal, Other, Speaker fees: Novartis; Financial Interests, Personal, Other, Speaker fees: Pierre Fabre; Financial Interests, Personal, Other, Co-inventor and patent holder with share options of a biomarker under development: Inbiomotion. All other authors have declared no conflicts of interest.