Oh Kyu Yoon (Foster City, United States of America)
Gilead Sciences, IncAuthor Of 1 Presentation
168P - Sacituzumab govitecan (SG) efficacy in patients with metastatic triple-negative breast cancer (mTNBC) by HER2 immunohistochemistry (IHC) status: Findings from the Phase 3 ASCENT study (ID 176)
- Sara A. Hurvitz (Los Angeles, United States of America)
- Aditya Bardia (Boston, United States of America)
- Kevin Punie (Leuven, Belgium)
- Kevin Kalinsky (Atlanta, United States of America)
- Javier Cortes (Madrid and Barcelona, Spain)
- Joyce O'Shaughnessy (Dallas, United States of America)
- Lisa A. Carey (Chapel Hill, United States of America)
- Hope S. Rugo (San Francisco, United States of America)
- Oh Kyu Yoon (Foster City, United States of America)
- Yang Pan (Foster City, United States of America)
- Rosemary J. Delaney (Foster City, United States of America)
- Scott Hofsess (Foster City, United States of America)
- Paul Hodgkins (Foster City, United States of America)
- See-Chun Phan (Foster City, United States of America)
- Veronique Dieras (Rennes, France)
Abstract
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. ISH, in situ hybridization; HR, hazard ratio; IHC, immunohistochemistry; mPFS, median progression-free survival; mOS, median overall survival, ORR, objective response rate; SG, sacituzumab govitecan; TPC, treatment of physician’s choice ∗HER2-Low defined as IHC1+ or ICH2+ and ISH-neg
HER2 IHC0 HER2-Low∗ SG (n=149) TPC (n=144) SG (n=63) TPC (n=60) mPFS, mo 4.3 1.6 6.2 2.9 HR (95% CI) 0.38 (0.28-0.50) 0.44 (0.27-0.72) mOS, mo 11.3 5.9 14.0 8.7 HR (95% CI) 0.51 (0.39-0.66) 0.43 (0.28-0.67) ORR, n (%) 46 (31) 5 (3) 20 (32) 5 (8)
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.