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LBA3 - Patritumab deruxtecan (HER3-DXd) in early-stage HR+/HER2- breast cancer: final results of the SOLTI TOT-HER3 window of opportunity trial (ID 303)
- Aleix Prat (Barcelona, Spain)
- Claudette Falato (Barcelona, Spain)
- Laia Pare Brunet (Barcelona, Spain)
- Olga Martinez Saez (Barcelona, Spain)
- Juan Miguel Cejalvo Andujar (Valencia, Spain)
- Mireia Margeli Vila (Badalona, Spain)
- Pablo Tolosa (Madrid, Spain)
- Francisco Javier Salvador Bofill (Seville, Spain)
- Josefina Cruz Jurado (San Cristobal de la Laguna, Spain)
- Blanca Gonzalez-Farre (Barcelona, Spain)
- Esther Sanfeliu Torres (Barcelona, Spain)
- Eva M. Ciruelos (Madrid, Spain)
- Martin Espinosa-Bravo (Barcelona, Spain)
- Yann Izarzugaza Peron (Madrid, Spain)
- Sonia Pernas Simon (L'Hospitalet de Llobregat, Spain)
- Stephen Esker (Basking Ridge, Spain)
- Pang-Dian Fan (Edison, United States of America)
- Juan M. Ferrero-Cafiero (Barcelona, Spain)
- Tomas Pascual (Barcelona, Spain)
- Ana Mafalda Antunes De Melo e Oliveira (Barcelona, Spain)
Abstract
Background
SOLTI TOT-HER3 study (NCT04610528) previously reported the biologic and clinical activity of HER3-DXd, a HER3 directed antibody drug conjugate, across the first 30 patients (Prat A, SABCS 2021). Here, we present the efficacy and safety results across all patients in the initial study cohort.
Methods
This window of opportunity, multicenter, pre-operative trial enrolled patients with untreated HR+/HER2- operable (≥1 cm) breast cancer (BC). Patients were categorized based on pre-treatment (pre-) ERBB3 mRNA levels and received a single dose of HER3-DXd (6.4 mg/kg). Primary objective was to evaluate the CelTIL score (Nuciforo P, Ann Oncol 2018) variation between pre- and post-treatment (C1D21) samples. Clinical, proteomic and genomic variables were associated with CelTIL changes. Adverse events (AEs) were graded according to CTCAE v5.0.
Results
Overall, 78 patients were enrolled and 77 were evaluable for the primary endpoint. Baseline characteristics were: mean age 53 years; median tumor size 21 mm; cN0 71%; mean Ki67 27%. Based on pre-ERBB3, tumors were classified as high (n=21), medium (n=21), low (n=21) and ultralow (n=14). All PAM50 subtypes were identified: Luminal (Lum) A 52%, LumB 41%, HER2-Enriched 3% and Basal-like 4%. The overall response rate was 45%. CelTIL increased significantly at C1D21 (mean diff.+6.8, p<0.001). This increase was observed among responders (p<0.001) but not in patients with stable disease (p=0.135). Non-Lum subtypes and high Risk Of Recurrence score were associated with high CelTIL response. Pre-ERBB3 was not associated with CelTIL change or clinical response. Paired Ki67 significantly decreased (p<0.001), while ERBB3 mRNA did not (p=0.13). At C1D21, immune genes were induced and proliferation genes were suppressed (False Discovery Rate=5%). Overall, 74 (95%) patients reported any grade AEs. Most common grade 3-4 AEs were: neutropenia (n=6), ALT increase (n=2) and diarrhea (n=1).
Conclusions
In untreated early HR+/HER2- BC, a single dose of HER3-DXd led to clinically meaningful response, increased immune infiltration and suppression of proliferation across varied levels of baseline ERBB3 mRNA. The safety profile was consistent with that previously reported.
Clinical trial identification
NCT04610528, released on October 30th 2020.
Legal entity responsible for the study
SOLTI Cancer Research Group.
Funding
Daiichi Sankyo.
Disclosure
A. Prat: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Institutional, Other, Contracted research: Roche, Nanostring, Novartis, Roche, Pfizer; Financial Interests, Personal, Invited Speaker, Lecture fees: Pfizer, Novartis, Amgen, BMS, Nanostring, Contracted research, Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Novartis, Pfizer, Amgen, BMS, Puma, Oncolytics, MSD, Guardant Health, Lilly; Financial Interests, Institutional, Invited Speaker, Lecture fees: Nanostring; Financial Interests, Institutional, Invited Speaker, Clinical trials: Daiichi Sankyo; Financial Interests, Personal, Expert Testimony, Advisory role/consultancy: Peptomyc; Financial Interests, Institutional, Other, Clinical trials: Lilly, Roche, Amgen, Boehringer; Financial Interests, Institutional, Other, Contracted research: Boehringer, Sysmex Europa GmbH, Medica Scientia inno. Research, Celgene, Astellas; Financial Interests, Personal, Invited Speaker, Leadership role: Reveal Genomics, SL.; Non-Financial Interests, Institutional, Other, Leadership roles: Patronage committee: SOLTI Foundation, Actitud Frente al Cáncer Foundation. O. Martinez Saez: Financial Interests, Personal, Invited Speaker: Novartis, Eisai; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Other, Travel expenses: Roche. J.M. Cejalvo Andujar: Financial Interests, Personal, Speaker’s Bureau: Novartis, Pfizer, Roche. M. Margeli Vila: Financial Interests, Personal, Advisory Board: Novartis, Roche, Pfizer; Financial Interests, Personal, Research Grant: Roche, AstraZeneca, Eisai, Novartis, Pfizer. P. Tolosa: Financial Interests, Personal, Speaker’s Bureau: Pfizer, Novartis, Roche, Eli Lilly, AstraZeneca. J. Cruz Jurado: Financial Interests, Personal, Advisory Role: AstraZeneca, Roche, Novartis, PharmaMar, Eisai, Lilly, Amgen, GlaxoSmithKline, Seagen, Daiichi Sankyo, Pfizer; Financial Interests, Personal, Speaker’s Bureau: GlaxoSmithKline, AstraZeneca, Roche, Novartis, PharmaMar, Eisai, Lilly, Celgene, Astellas, Amgen, Pfizer. E.M. Ciruelos: Financial Interests, Personal, Other, Speakers Bureau, Educational activities: Roche, Lilly; Financial Interests, Personal, Invited Speaker, Symposia and Educational activities: Roche; Financial Interests, Personal, Advisory Board, Non-permanent advisor: Roche, Lilly, Novartis, Pfizer, AstraZeneca, Daiichi Sankyo, MSD; Financial Interests, Personal, Invited Speaker, Symposia and Education: Lilly; Financial Interests, Personal, Invited Speaker, Educational activities: Pfizer; Financial Interests, Institutional, Funding, PI for Patricia 2 trial (sponsor: SOLTI Group): Pfizer; Financial Interests, Institutional, Funding, PI for Prometeo 2 trial (sponsor: SOLTI Group): Pfizer; Financial Interests, Institutional, Funding, PI for TATEN trial (sponsor: SOLTI Group): MSD; Financial Interests, Institutional, Funding, PI for NEREA trial (sponsor: SOLTI Group): PUMA; Financial Interests, Institutional, Funding, PI for ATREZZO trial (sponsor: SOLTI Group): Roche; Non-Financial Interests, Invited Speaker, Non-profit organization dedicated to breast cancer research: SOLTI Cooperative Group; Non-Financial Interests, Advisory Role, Scientific Evaluator at ISCIII (Spanish Government Academic Research Platform): Instituto de Salud Carlos III. S. Pernas Simon: Financial Interests, Personal, Advisory Role: AstraZeneca, Daiichi Sankyo, Polyphor, Novartis, Seattle Genetics, Roche, Eisai, Pierre Fabre, Lilly. T. Pascual: Financial Interests, Personal, Invited Speaker: Pfizer, AstraZeneca, Lilly. M. Oliveira: Financial Interests, Personal, Other: Roche, Pierre Fabre, Novartis, Eisai, Immunomedics, AstraZeneca, Genentech, Seagen, Boehringer Ingelheim, PUMA Biotechnology, GSK, Zenith Epigenetics. Financial Interests, Personal, Advisory Role: Roche, GSK, PUMA Biotechnology, AstraZeneca, Pierre Fabre iTEOS. All other authors have declared no conflicts of interest.
162O - Primary analysis from DS8201-A-U105: A 2-part, open label, phase 1b trial assessing trastuzumab deruxtecan (T-DXd) with nivolumab (nivo) in patients (pts) with HER2-expressing advanced breast cancer (ID 304)
- Erika P. Hamilton (Nashville, United States of America)
- Charles L. Shapiro (New York, United States of America)
- Valentina Boni (Madrid, Spain)
- Miguel Martin Jimenez (Madrid, Spain)
- Gianluca Del Conte (Milan, Italy)
- Javier Cortes (Madrid and Barcelona, Spain)
- LAILA Agrawal (Louisville, United States of America)
- Hendrik-Tobias Arkenau (London, United Kingdom)
- Antoinette R. Tan (Charlotte, United States of America)
- Philip R. Debruyne (Cambridge, United Kingdom)
- Anna R. Minchom (London, United Kingdom)
- Annemie Rutten (Wilrijk, Belgium)
- Frances Valdes-Albini (Miami, United States of America)
- Evan Yu (Seattle, United States of America)
- Fumitaka Suto (Basking Ridge, United States of America)
- Fu-Chih Cheng (Basking Ridge, United States of America)
- Bincy Augustine (Basking Ridge, United States of America)
- Ben Cheng (Basking Ridge, United States of America)
- Daniel Barrios (Basking Ridge, United States of America)
- Sara A. Hurvitz (Los Angeles, United States of America)
Abstract
Background
In DESTINY-Breast01 (NCT03248492), T-DXd showed efficacy and safety in pts with HER2+ metastatic breast cancer (MBC) with prior T-DM1. Preclinical models showed that T-DXd combined with an anti–PD-1 antibody had greater efficacy vs either agent alone (Iwata Mol Cancer Ther 2018). This was a 2-part, open-label, multicenter, phase 1b study of T-DXd with nivo in pts with HER2-expressing MBC or advanced urothelial cancer (NCT03523572). Primary results from part 2 for MBC pts are reported.
Methods
Pts were immunotherapy naive with centrally confirmed HER2+ (IHC 3+ or IHC 2+/ISH+) MBC after T-DM1 or HER2 low (IHC 1+ or IHC 2+/ISH-) MBC after standard-of-care. Pts received the recommended dose for expansion T-DXd 5.4 mg/kg and nivo 360 mg IV Q3W. The primary endpoint was confirmed ORR (cORR) assessed by independent central review (ICR) per RECIST v1.1. Secondary endpoints included progression-free survival (PFS), duration of response (DOR), and safety.
Results
At the primary analysis data cutoff (July 22, 2021), 48 pts (HER2+, n = 32; HER2 low, n = 16) received T-DXd and nivo. Median follow-up duration was 18.7 mo for HER2+ pts and 12.7 mo for HER2-low pts. The cORR by ICR was 65.6% (95% CI, 46.8-81.4) and 50% (95% CI, 24.7-75.3); median PFS was 11.6 mo (95% CI, 6.9-NE) and 7.0 mo (95% CI, 2.3-10.8); and median DOR was NE (95% CI, 7.9-NE) and 5.5 mo (95% CI, 2.8-8.0) for HER2+ and HER2 low pts, respectively. Overall, median treatment duration was 7.9 mo for T-DXd and 5.8 mo for nivo. In parts 1 and 2 (T-DXd 5.4 mg/kg, nivo 360 mg; n = 48), TEAEs grade ≥3 occurred in 50.0% of pts; nausea (56.3%) was the most common any-grade TEAE; and 7 (14.6%) HER2+ pts had adjudicated drug-related interstitial lung disease (6 grade 2; 1 grade 5).
Conclusions
Results of T-DXd plus nivo show antitumor activity consistent with previously reported data for T-DXd monotherapy in HER2+ BC, with no discernable benefit with the addition of nivo in this late-line setting. Data from the small HER2-low cohort are insufficient to determine the effects of PD-1/PD-L1 combination therapy. The combination safety profile was similar to that of each study drug as monotherapy.
Clinical trial identification
NCT03523572.
Editorial acknowledgement
Under the guidance of authors, assistance in medical writing and editorial support was provided by Jill Seabrook, PhD, of ApotheCom, and was funded by Daiichi Sankyo, Inc.
Legal entity responsible for the study
Daiichi Sankyo, Inc. and AstraZeneca.
Funding
Daiichi Sankyo, Inc. and AstraZeneca.
Disclosure
E.P. Hamilton: Financial Interests, Institutional, Advisory Board: Arcus, Arvinas, Black Diamond, Boehringer Ingelheim, CytomX, Daiichi Sankyo, Dantari, Deciphera Pharmaceuticals, Eisai, H3 Biomedicine, iTeos, Janssen, Lilly, Loxo, Merck, Mersana, Novartis, Pfizer, Puma Biotechnology, Relay Therapeutics, Roche/Genentech; Financial Interests, Institutional, Research Grant: AbbVie, Acerta Pharma, ADC Therapeutics, AKESOBIO Australia, Amgen, Aravive, 3 ArQule, Arvinas, AstraZeneca, AtlasMedx, Black Diamond, Boehringer Ingelheim, Clovis, Compugen, Curis, CytomX, Daiichi Sankyo, Dana Farber Cancer Inst., Deciphera, eFFECTOR The. C.L. Shapiro: Financial Interests, Personal, Other, Honoraria: UF Breast Symposium; Financial Interests, Personal, Advisory Board: 2nd MD, Anthenum, Gilead; Financial Interests, Personal, Other, Royalties: UptoDate. V. Boni: Financial Interests, Personal, Other, Honoraria: Director of Clinical Cancer Research, NEXT Madrid, Universitary Hospital QuirónSalud Pozuelo; Financial Interests, Institutional, Other, Honoraria: AbbVie; ACEO; Adaptaimmune; Amcure; Amgen; AstraZeneca; BMS Cytomx; GSK; Genentech/Roche; H3; Incyte; Janssen; Kura; Lilly; Loxo; Nektar; Macrogenics; Menarini; Merck; Merus; Nanobiotix; Novartis; Pfizer; PharmaMar; Principia; Puma; Sanofi; Taiho; Tesaro; Financial Interests, Personal, Advisory Board: Puma Biotechnology; Ideaya Biosciences; Loxo Therapeutics, CytomX Therapeutics; Guidepoint; Oncoart; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly. M. Martin Jimenez: Financial Interests, Personal, Other, Honoraria: Roche, Novartis, Daiichi Sankyo, Seagen, AstraZeneca, Pfizer, Lilly; Financial Interests, Personal, Advisory Board: Roche, Novartis, Daiichi Sankyo, Seagen, AstraZeneca, Pfizer, Lilly; Financial Interests, Institutional, Research Grant: Roche, Puma, Novartis. G. Del Conte: Financial Interests, Personal, Advisory Board: Novartis, BMS; Financial Interests, Personal, Other, Travel Expenses: Janssen, Astellas, Pfizer. J. Cortés: Financial Interests, Personal, Other, Honoraria: Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp&Dohme, Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Roche, Celgene, Cellestia, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Merck Sharp&Dohme, GSK, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymework; Financial Interests, Personal, Stocks/Shares: MedSIR; Financial Interests, Institutional, Research Grant: Roche, Ariad pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, F.Hoffman- La Roche, Guardanth health, Merck Sharp&Dohme, Pfizer, Piqur Therapeutics, Puma C, Queen Mary University of London; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche, Novartis, Eisai, Pfizer, Daiichi Sankyo, AstraZeneca. L. Agrawal: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Immunomedics, Breast Cancer Index; Financial Interests, Personal, Speaker’s Bureau: Lilly. H. Arkenau: Financial Interests, Personal, Advisory Board: Roche, LabGenius, Cell Centric, Daiichi Sankyo, Bicycle Therapeutics; Guardant Health, BioNTech, Bayer, Beigene, Servier; Financial Interests, Personal, Other, Honoraria: Bicycle Therapeutics, BioNTech, Bayer, Beigene, Servier, Roche and Guardant Health; Financial Interests, Personal, Other, Travel Expenses: Amgen; Financial Interests, Personal, Full or part-time Employment: Sarah Cannon. A.R. Tan: Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Institutional, Research Grant: Daiichi Sankyo. P.R. Debruyne: Financial Interests, Personal, Other, Honoraria: BMS, Merck/Pfizer, MSD, Roche, Bayer; Financial Interests, Personal, Stocks/Shares: Alkermes; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Janssen. A.R. Minchom: Financial Interests, Personal, Other, Honoraria: Chugai Pharmaceuticals, Novartis Oncology, Faron Pharmaceuticals, Bayer Pharmaceuticals; Financial Interests, Personal, Advisory Board: Janssen Pharmaceuticals, Merck Pharmaceuticals, Takeda Pharmaceuticals and Genmab Pharmaceuticals; Financial Interests, Personal, Other, Travel Expenses: Amgen Pharmaceuticals and LOXO Oncology. E. Yu: Financial Interests, Personal, Advisory Board: Advanced Accelerator Applications, Bayer, Janssen, Merck, Exelus, Clovis, AbbVie, Sanofi; Financial Interests, Invited Speaker: Daiichi Sankyo, Dendreon, Taiho, Merck, Seagen, Blue Earth, Bayer, Lantheus. F. Suto, F. Cheng, B. Augustine, B. Cheng, D. Barrios: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo, Inc. S.A. Hurvitz: Financial Interests, Institutional, Research Grant: Ambrx, Amgen, AstraZeneca, Arvinas, Bayer, Cytomx, Daiichi Sankyo, Dignitana, Genentech/Roche, Gilead, GSK, Immunomedics, Eli Lilly, Macrogenics, Novartis, Pfizer, OBI Pharma, Orinove, Pieris, Puma, Radius, Sanofi, Seattle Genetics/Seagen, Zymeworks, Pho; Financial Interests, Personal, Principal Investigator: Novartis, Daiichi Sankyo, Seagen, GNE/Roche; Financial Interests, Personal, Advisory Board: Novartis, Lilly, Daiichi Sankyo/AZ, GNE/Roche, Sanofi; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Lilly; Non-Financial Interests, Personal, Other, Uncompensated consulting/ad boards: 4DPharma, Ambrx, Amgen, Artios, Arvinas, Daiichi Sankyo, Dantari, Genentech/Roche, Immunomedics, Macrogenics, Eli Lilly, Novartis, NK Max, Pieris, Pyxis, Seagen, Biotheranostics. All other authors have declared no conflicts of interest.
Invited Discussant LBA3 and 162O (ID 305)
163O - Patient-reported outcomes (PROs) from DESTINY-Breast03, a randomized phase 3 study of trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients (pts) with HER2-positive (HER2+) metastatic breast cancer (MBC) (ID 306)
- Giuseppe Curigliano (Milan, Italy)
- Kyle Dunton (Munich, Germany)
- Mats Rosenlund (Munich, Germany)
- Martin Janek (Braine-l'Alleud, Belgium)
- Jillian Cathcart (Basking Ridge, United States of America)
- Yali Liu (Basking Ridge, United States of America)
- Peter A. Fasching (Erlangen, Germany)
- Hiroji Iwata (Nagoya, Japan)
Abstract
Background
In DESTINY-Breast03 (NCT03529110), T-DXd showed superior progression-free survival by BICR vs T-DM1 (HR, 0.28 [95% CI, 0.22-0.37]; P < 0.001) and manageable safety in pts with HER2+ MBC. PRO measures incorporate pts’ perspective in clinical trials to assess effect of treatment on health-related quality of life (QoL). Here, PROs and hospitalization rate for T-DXd vs T-DM1 (May 21, 2021, data cutoff) are reported.
Methods
Pts with HER2+ (IHC 3+ or IHC 2+/ISH+) MBC whose disease progressed on or after trastuzumab and a taxane were assigned 1:1 to T-DXd or T-DM1. PRO endpoints were assessed before infusion on day 1 of the first 3 21-day cycles, then every 2 cycles, at end of treatment, at 40-days’ follow-up, then every 3 months until end of follow-up; endpoints included European Organization for Research and Treatment of Cancer QoL questionnaires (EORTC QLQ-C30; primary variable: global health status [GHS]/QoL scale score) and the EuroQol 5-dimension 5-level (EQ-5D-5L) visual analog scale (VAS). Analyses included change from baseline (CFB) and time to definitive deterioration (TDD). Hospitalization-related endpoints were also measured.
Results
Compliance for questionnaires was >97% at baseline and >80% for cycles 3-29. QLQ-C30 baseline GHS scores recorded for T-DXd (n = 253) and T-DM1 (n = 260) were similar. At end of treatment, mean CFB was not meaningfully different vs baseline (<10-point CFB) in both arms. Median TDD of QLQ-C30 GHS was 9.7 mo for T-DXd vs 8.3 mo for T-DM1 (HR, 0.88 [95% CI, 0.70-1.11]), and all prespecified QLQ-C30 subscales presented longer TDD with T-DXd, including emotional functioning (HR, 0.69 [95% CI, 0.53-0.89]) and pain (HR, 0.75 [95% CI, 0.59-0.95]). Median TDD of EQ-5D-5L VAS was 13.2 mo for T-DXd vs 8.5 mo for T-DM1 (HR, 0.77 [95% CI, 0.61-0.98]). With T-DXd vs T-DM1, 18 pts (6.9%) vs 19 pts (7.2%) were hospitalized; median time to first hospitalization was 219.5 vs 60.0 days, respectively.
Conclusions
The improved efficacy and manageable toxicity reported previously for T-DXd, together with this evidence of maintained or improved QoL supports the overall benefit of T-DXd for pts with HER2+ MBC.
Clinical trial identification
NCT03529110.
Editorial acknowledgement
Under the guidance of authors, assistance in medical writing and editorial support was provided by Marianna B. Johnson, PhD, and Eileen McIver, PhD, of ApotheCom, and was funded by Daiichi Sankyo, Inc.
Legal entity responsible for the study
Daiichi Sankyo, Inc., and AstraZeneca.
Funding
Daiichi Sankyo, Inc., AstraZeneca.
Disclosure
G. Curigliano: Financial Interests, Personal, Other, Honoraria: BMS, Pfizer, Novartis, Lilly, Roche, AstraZeneca, Daiichi Sankyo, Exact Sciences, Seagen, Gilead, Celcuity; Financial Interests, Personal, Advisory Board, Honoraria: BMS, Pfizer, Novartis, Lilly, Roche, AstraZeneca, Daiichi Sankyo, Exact Sciences, Seagen, Gilead, Celcuity; Financial Interests, Personal, Speaker’s Bureau: Pfizer, Novartis, Lilly, Roche, AstraZeneca, Daiichi Sankyo, Exact Sciences, Seagen; Financial Interests, Personal, Research Grant: Merck; Financial Interests, Personal, Other, Travel expenses, including accommodations: Pfizer, Roche; Financial Interests, Institutional, Research Grant: BMS, Pfizer, Novartis, Lilly, Roche, AstraZeneca, Daiichi Sankyo, Exact Sciences, Seagen, Gilead, Celcuity; Financial Interests, Personal, Officer: ESMO, LILT, EUSOMA; Financial Interests, Personal, Other: National Health Council. K. Dunton: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. M. Rosenlund: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. M. Janek: Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc.; Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. J. Cathcart: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. Y. Liu: Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo, Inc.; Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. P.A. Fasching: Financial Interests, Personal, Other, Honoraria: Novartis, Pfizer, Daiichi Sankyo, Eisai, Merck Sharp & Dohme, Lilly, Pierre Fabre, Seagen, Roche, Hexal, Agendia, Sanofi Aventis, Gilead; Financial Interests, Personal, Advisory Board: Novartis, Pfizer, Daiichi Sankyo, Eisai, Merck Sharp & Dohme, Lilly, Pierre Fabre, Seagen, Roche, Hexal, Agendia, Sanofi Aventis, Gilead; Financial Interests, Institutional, Research Grant: Cepheid, BioNTech; Financial Interests, Personal, Officer: TRIO. H. Iwata: Financial Interests, Personal, Other, Honoraria: Daiichi Sankyo, Chugai, AstraZeneca, Lilly, MSD, Pfizer; Financial Interests, Personal, Advisory Board: Daiichi Sankyo, Chugai, AstraZeneca, Sanofi, Lilly, MSD, Pfizer; Financial Interests, Personal, Research Grant: Daiichi Sankyo, Chugai, AstraZeneca, Lilly, MSD, Pfizer; Financial Interests, Institutional, Research Grant: Daiichi Sankyo, Chugai, AstraZeneca, Lilly, MSD, Pfizer.
164O - Health-Related Quality of Life (HRQoL) With Pembrolizumab (pembro) + Chemotherapy (chemo) vs Placebo (pbo) + Chemo as 1L Treatment for Advanced Triple-Negative Breast Cancer (TNBC): Results From KEYNOTE-355 (ID 307)
- David W. Cescon (Toronto, Canada)
- Peter Schmid (London, United Kingdom)
- Hope S. Rugo (San Francisco, United States of America)
- Seock-Ah Im (Seoul, Korea, Republic of)
- Mastura Md Yusof (Kuala Lumpur, Malaysia)
- Carlos E. Gallardo (Providencia, Chile)
- Oleg Lipatov (Republic of Bashkortostan, Russian Federation)
- Carlos H. Barrios (Porto Alegre, Brazil)
- Jose Manuel Perez Garcia (Barcelona, Spain)
- Hiroji Iwata (Nagoya, Japan)
- Norikazu Masuda (Nagoya, Japan)
- Marco Antonio Torregroza Otero (Monteria, Colombia)
- Erhan Gokmen (Izmir, Turkey)
- Sherene Loi (Melbourne, Australia)
- Amin Haiderali (Kenilworth, United States of America)
- Xuan Zhou (North Wales, United States of America)
- Zifang Guo (Kenilworth, United States of America)
- Allison Martin Nguyen (Kenilworth, United States of America)
- Javier Cortes (Madrid and Barcelona, Spain)
Abstract
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. aBased on constrained longitudinal data analysis model (two-sided P value). bBased on stratified Cox regression model; P value based on stratified log-rank test (one-sided).
Change from baseline to wk 15a Between-group difference (pembro vs pbo) QLQ-C30 GHS/QoL −1.81 (−6.92 to 3.30); P = 0.4865 QLQ-C30 emotional functioning −1.43 (−7.03 to 4.16); P = 0.6149 QLQ-C30 physical functioning −1.05 (−6.59 to 4.50); P = 0.7102 EQ-5D VAS 0.18 (−5.04 to 5.39); P = 0.9468 TTDb HR (Pembro vs Pbo) (95% CI); P Value QLQ-C30 GHS/QoL 1.00 (0.72 to 1.40); P = 0.5137 QLQ-C30 emotional functioning 1.28 (0.88 to 1.85); P = 0.9039 QLQ-C30 physical functioning 1.26 (0.90 to 1.77); P = 0.9194
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.