Abstract 198P
Background
SG is a Trop-2–directed antibody-drug conjugate approved in multiple countries for pts with pretreated mTNBC and in the US for pts with pretreated HR+/HER2— metastatic breast cancer. SG has a manageable safety profile, with neutropenia and diarrhea as the most common grade ≥3 adverse events (AEs). Here, we evaluated the relationship of these two AEs with clinical outcomes in pts with mTNBC.
Methods
Pts with mTNBC who received SG in the phase III ASCENT study (NCT02574455) were included. A post hoc analysis was conducted to estimate the relationship of AEs (neutropenia [including febrile neutropenia] or diarrhea, separately) with clinical outcomes (progression-free survival and overall survival).
Results
For the 254 SG-treated pts in this analysis, baseline characteristics were similar among pts who did and did not experience neutropenia or diarrhea. For SG, the incidence of grade ≥3 neutropenia was 54% (n=138) and grade ≥2 diarrhea was 32% (n=81); no grade 5 events occurred. The relationship between occurrence of grade ≥3 neutropenia and grade ≥2 diarrhea with outcomes among pts who received SG is described in the table.
Conclusions
In this post hoc analysis of ASCENT, clinical outcomes for pts with pretreated mTNBC who did and did not experience AEs of grade ≥3 neutropenia or grade ≥2 diarrhea were consistent with the overall intention-to-treat population and were not adversely impacted by the occurrence of these AEs. Active monitoring and early intervention using management strategies for neutropenia and diarrhea in line with established guidelines may allow for longer treatment durations and sustained benefit from SG. Table: 198P
| Grade ≥2 diarrhea | Grade ≥3 neutropenia | ITT | ||||
| SG with (n=81) | SG without (n=173) | SG with (n=138) | SG without (n=116) | SG (n=267) | TPC (n=262) | |
| Median PFS, mo (95% CI) | 6.9 (4.2-8.3) | 4.9 (3.7-5.7) | 5.6 (4.0-6.5) | 4.9 (4.1-5.9) | 4.8 (4.1-5.8) | 1.7 (1.5-2.5) |
| HR (95% CI) | 0.72 (0.52-0.98) | 0.91 (0.68-1.21) | 0.43 (0.35-0.54) | |||
| Median OS, mo (95% CI) | 14.3 (11.8-16.7) | 10.9 (9.5-13.8) | 13.5 (10.8-14.5) | 11.2 (10.1-14.1) | 11.8 (10.5-13.8) | 6.9 (5.9-7.7) |
| HR (95% CI) | 0.69 (0.50-0.94) | 0.99 (0.74-1.32) | 0.51 (0.41-0.62) |
ITT, intention-to-treat; OS, overall survival; PFS, progression-free survival; SG, sacituzumab govitecan; TPC, treatment of physician’s choice.
Clinical trial identification
NCT02574455.
Editorial acknowledgement
Hameda Khandaker, PhD, and Shala Thomas, PhD, CMPP, at Team 9 Science.
Legal entity responsible for the study
Gilead Sciences, Inc.
Funding
Gilead Sciences, Inc.
Disclosure
E. de Azambuja: Financial Interests, Personal, Advisory Board: Roche/GNE, Novartis, Seagen; Financial Interests, Personal, Invited Speaker: Zodiac, Libbs, Pierre Fabre, Lilly, Astra-Zeneca; Financial Interests, Institutional, Research Grant: Roche/GNE, AstraZeneca, GSK/Novartis, Servier; Financial Interests, Institutional, Other, Travel Grant: Roche/GNE; Financial Interests, Institutional, Invited Speaker: MSD, ABCSG, Nektar, Gilead, Immunomedics, Synthon, Odonate Therapeutics; Financial Interests, Invited Speaker, Chair of the Gilead Sciences Research Scholars Program in Solid Tumours: Gilead; Financial Interests, Invited Speaker, Aphinity, Lorelei, Impassion03: Roche; Financial Interests, Invited Speaker, AURORA: Breast International Group; Financial Interests, Invited Speaker, Olympia: Astra-Zeneca; Financial Interests, Personal, Other, Travel grant: Astra-Zeneca; Non-Financial Interests, Advisory Role, Member of the cardio-oncology council: European Society for Cardiology (ESC); Non-Financial Interests, Advisory Role, Belgium governmental institution for cancer: KCE; Non-Financial Interests, Other, Editorial board member: ESMO Open; Non-Financial Interests, Advisory Role: Anticancer Fund. M. Lambertini: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Lilly, Novartis, Pfizer, Exact Sciences, MSD, Seagen, Gilead; Financial Interests, Personal, Invited Speaker: Takeda, Sandoz, Ipsen, Libbs, Knight, Daiichi Sankyo, Lilly, Pfizer, Novartis, Roche; Financial Interests, Personal, Other, Travel grant to attend ASCO 2022: Gilead; Financial Interests, Institutional, Invited Speaker, 2-year research grant paid to my Institution: Gilead. H.S. Rugo: Financial Interests, Personal, Funding: Puma Biotechnology, Mylan, Samsung Bioepis; Financial Interests, Institutional, Funding: Macrogenics, OBI Pharma, Pfizer, Novartis, Lilly, Genentech, Merck, Odonate Therapeutics, Daiichi Sankyo, Seattle Genetics, Sermonix Pharmaceuticals, AstraZeneca, Gilead Sciences, Ayala Pharmaceuticals. A. Bardia: Financial Interests, Personal, Advisory Board: Pfizer, Novartis, Genentech, Merck, Sanofi, Eisai, Lilly, Mersana, AstraZeneca/Daiichi, Menarini, Gilead; Financial Interests, Personal, Royalties: UpToDate; Financial Interests, Institutional, Invited Speaker: Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics/Gilead, Daiichi Pharma/AstraZeneca, Eli Lilly.; Non-Financial Interests, Principal Investigator: Gilead, Mersana, AstraZeneca/Daiichi, Novartis, Pfizer, Genentech, Lilly, Merck, Sanofi. S.M. Tolaney: Financial Interests, Personal, Advisory Board, Ad Board Participant/Consultant: AstraZeneca, Eli Lilly; Financial Interests, Personal, Advisory Board, Ad board participant/Consultant: Pfizer; Financial Interests, Personal, Advisory Board, Ad board participant/consultant: Novartis, Gilead, Genentech/Roche, Eisai, Sanofi, Seagen, Daiichi Sankyo, 4D Pharma, ARC Therapeutics; Financial Interests, Personal, Advisory Board, Ad Board participant/consultant: Merck; Financial Interests, Personal, Advisory Board, Ad board participant: Bristol Myers Squibb, Mersana Therapeutics, Ellipses Pharma; Financial Interests, Personal, Other, Steering Committee Member/Consultant: CytomX; Financial Interests, Personal, Other, Consultant: Blueprint Medicines; Financial Interests, Personal, Advisory Board, Advisory Board Participation: Zymeworks; Financial Interests, Personal, Advisory Board, Advisory Board participation: Zentalis, OncXerna, Myovant, Bayer, Zetagen, Infinity Therapeutics, Umoja Biopharma; Financial Interests, Personal, Advisory Board, Advisory board participation: Reveal Genomics; Financial Interests, Personal, Advisory Board, Advisory Board participation/consulting: Menarini/Stemline; Financial Interests, Personal, Other, Consulting: Aadi BioPharma; Financial Interests, Institutional, Funding: AstraZeneca, Eli Lilly, Pfizer, Sanofi, Seagen, Odonate, Cyclacel, Exelixis, Gilead, Bristol Myers Squibb, Eisai, Merck, Novartis, Nektar, Genentech/Roche; Financial Interests, Personal and Institutional, Invited Speaker: CytomX. J. O'Shaughnessy: Financial Interests, Personal, Funding: AbbVie Inc., Agendia, Amgen Biotechnology, Aptitude Health, AstraZeneca, Bayer, Bristol Myers Squibb, Celgene Corporation, Clovis Oncology, Daiichi Sankyo, Eisai, G1 Therapeutics, Genentech, Gilead Sciences, GRAIL, Halozyme Therapeutics, Heron Therapeutics, Immunomedics, Ipsen Biopharmaceuticals, Lilly, Merck, Myriad, Nektar Therapeutics, Novartis, Pfizer, Pharmacyclics, Pierre Fabre Pharmaceuticals, Puma Biotechnology, Prime Oncology, Roche, Samsung Bioepis, Sanofi, Seagen, Syndax Pharmaceuticals, Taiho Oncology, Takeda, Synthon. R.J. Delaney: Financial Interests, Personal, Full or part-time Employment: Gilead Sciences, Inc.; Financial Interests, Personal, Stocks/Shares: Gilead Sciences, Inc. S. Zha: Financial Interests, Personal, Full or part-time Employment: Gilead Sciences, Inc., University of Pittsburgh; Financial Interests, Personal, Stocks/Shares: Gilead Sciences, Inc.; Financial Interests, Personal, Funding: Gilead Sciences, Inc. T. Valdez: Financial Interests, Personal, Full or part-time Employment: Gilead Sciences, Inc.; Financial Interests, Personal, Stocks/Shares: Gilead Sciences, Inc. K. Kalinsky: Financial Interests, Personal, Advisory Board: Daiichi Sankyo, Eli Lilly, Pfizer, Novartis, Eisai, AstraZeneca, Immunomedics, Merck, Seattle Genetics, Cyclacel, Oncosec, 4D Pharma, Puma; Financial Interests, Personal, Stocks/Shares, Employment + Stock = spouse: Grail; Financial Interests, Personal and Institutional, Invited Speaker, Consultant: Novartis, Eli Lilly, AstraZeneca, daicchi sankyo; Financial Interests, Personal and Institutional, Invited Speaker, consultant: Genentech; Financial Interests, Institutional, Invited Speaker, consultant: Pfizer; Financial Interests, Institutional, Invited Speaker: Seattle Genetics, Ascentantage; Financial Interests, Personal, Other, Consultant: Myovant, Takeda, Menarini; Financial Interests, Personal, Other, consultant: Menarini; Other, Support for attending meetings and/or travel: Eli Lilly, AstraZeneca, Pfizer; Other, Steering Committee: Immunomedics, AstraZeneca, Ambryx, Genentech. E. Agostinetto: Financial Interests, Personal, Funding: Eli Lilly, Sandoz, AstraZeneca, Novartis, Roche, Eli Lilly, Genetic, Istituto Gentili, Daiichi Sankyo. All other authors have declared no conflicts of interest.