389P - Efficacy and safety analyses by prior lines of chemotherapy from the phase III TROPiCS-02 study of sacituzumab govitecan (SG) vs treatment of physician’s choice (TPC) in patients (pts) with HR+/HER2- metastatic breast cancer (mBC)

Background

SG is a Trop-2–directed antibody-drug conjugate approved for pretreated HR+/HER2- (IHC 0, 1+, or 2+/ISH-) mBC in the US. In the TROPiCS-02 study, SG treatment showed statistically significant improvement in progression-free survival (PFS; hazard ratio [HR] 0.66; 95% confidence interval [CI] 0.53-0.83) and overall survival (OS; HR 0.79; 95% CI 0.65-0.96) vs TPC with manageable safety in pts with pretreated HR+/HER2- mBC (Rugo et al. ESMO 2022 ). Outcomes worsen with multiple prior lines of chemotherapy (LoT). We present a post-hoc analysis of outcomes with SG vs TPC by prior LoT from TROPiCS-02.

Methods

Pts with HR+/HER2- mBC and ≥ 1 endocrine therapy, taxane, and CDK4/6 inhibitor, and 2 to 4 prior LoT for mBC, were randomized to SG (10 mg/kg IV Days 1 and 8, Q3W) or TPC. The primary endpoint was PFS; secondary endpoints included OS, objective response rate (ORR), clinical benefit rate (CBR), and safety. This analysis included pts with 2 vs ≥ 3 prior LoT in the metastatic setting.

Results

543 pts were randomized to SG (n = 272; 113 (42%) had 2 prior LoT, 159 (58%) had ≥ 3) and TPC (n = 271; 120 (44%) had 2 prior LoT, 151 (56%) had ≥ 3). Baseline characteristics were similar in pts with 2 and ≥ 3 prior LoT and across treatments. Median PFS and OS were improved with SG vs TPC irrespective of prior LoT, with HR of 0.61 and 0.82 in pts with 2 prior LoT and 0.72 and 0.78 in pts with ≥ 3 prior LoT, respectively (Table). CBR was improved with SG vs TPC in pts with 2 and ≥ 3 prior LoT, ORR was improved in pts with 2 prior LoT, and the safety profile was similar in both subgroups (Table). Table: 389P

^aPer independent central review. ^bData cutoff: Jan 3, 2022; ^cJul 1, 2022.

Conclusions

Regardless of number of prior LoT, SG demonstrated improved efficacy vs TPC in pts with HR+/HER2- mBC, with manageable safety across subgroups. Findings are consistent with the ITT population, demonstrating the potential for pts to benefit from SG in earlier LoT. Table

Clinical trial identification

NCT03901339.

Editorial acknowledgement

Editorial support was provided by Ben Labbe, PhD, of Parexel and funded by Gilead Sciences, Inc.

Legal entity responsible for the study

Gilead Sciences, Inc.

Funding

Gilead Sciences, Inc.

Disclosure

J. Cortés: 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, Zymeworks, Reveal Genomics; Financial Interests, Personal, Invited Speaker: Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp & Dohme, Daiichi Sankyo; Financial Interests, Personal, Other, Consulting/advisor: Expres2ion Biotechnologies; Financial Interests, Personal, Stocks/Shares: MedSIR, Nektar Therapeutics; Financial Interests, Institutional, Research Grant: Roche, Ariad Pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, Guardanth health, Merck Sharp&Dohme, Pfizer, Piqur Therapeutics, Puma B, Queen Mary University of London; Other, Travel cost and expenses: Roche, Novartis, Eisai, Daiichi Sankyo, Pfizer, Gilead, AstraZeneca. F. Marmé: Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK/Tesaro, Clovis, Pfizer, Lilly; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Novartis, Roche, Gilead/immunomedics, EISAI, PharmaMar, GenomicHealth, Myriad, Seagen; Financial Interests, Institutional, Invited Speaker: Seagen, Daiichi Sankyo, GSK, AstraZeneca; Financial Interests, Institutional, Advisory Board: Roche, Immunicom; Financial Interests, Institutional, Local PI: Roche, Novartis, Eisai, MSD, Vaccibody, GSK; Financial Interests, Institutional, Coordinating PI: AstraZeneca, Roche, Gilead/Immunomedics, German Breast Group, AGO Research GmbH; Financial Interests, Institutional, Funding: AstraZeneca, Lilly, Seagen. P. Schmid: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, Pfizer, Puma, Roche, Gilead, Eisai, MSD, Seagen, Amgen, Celgene, Lilly; Financial Interests, Institutional, Research Grant: Astellas, AstraZeneca, Genentech, Novartis, Oncogenex, Roche, Medivation. H.S. Rugo: Financial Interests, Personal, Other, Consultancy/advisory support: PUMA, NAPO, Mylan, Daiichi Sankyo, Eisai; Financial Interests, Institutional, Local PI: Novartis, Lilly, Pfizer, Daiichi, AstraZeneca, Gilead Sciences, Inc., GSK, Sermonix Pharmaceuticals Ins., Pionyr Immunotherapeutics, Taiho Oncology, Inc., Veru Inc; Financial Interests, Institutional, Coordinating PI: OBI Pharma, Astellas Pharma Inc., F. Hoffmann-La Roche AG/Genentech, Inc., Merck; Financial Interests, Personal, Other, Travel support to academic meetings: Merck, AstraZeneca, Gilead; Non-Financial Interests, Advisory Role, I advise a number of companies without compensation: various. S.M. Tolaney: Financial Interests, Personal, Advisory Board, Ad board participant/consultant: 4D Pharma, ARC Therapeutics, Daiichi Sankyo, Eisai, Genentech/Roche, Gilead, Novartis, Sanofi, SeaGen; Financial Interests, Personal, Other, Consulting: Aadi BioPharma; Financial Interests, Personal, Advisory Board, Ad board participation: Artios, Incyte Corp, BeyondSprings; Financial Interests, Personal, Advisory Board, Ad Board Participant/Consultant: AstraZeneca, Eli Lilly; Financial Interests, Personal, Advisory Board, Advisory Board participation: Bayer, Infinity Therapeutics, Myovant, OncXerna, Umoja Biopharma, Zentalis, Zetagen; Financial Interests, Personal, Other, Consultant: Blueprint Medicines; Financial Interests, Personal, Advisory Board, Ad board participant: Bristol Myers Squibb, Ellipses Pharma, Mersana Therapeutics; Financial Interests, Personal, Other, Steering Committee Member/Consultant: CytomX; Financial Interests, Personal, Advisory Board, Advisory Board participation/consulting: Menarini/Stemline; Financial Interests, Personal, Advisory Board, Ad Board participant/consultant: Merck; Financial Interests, Personal, Advisory Board, Ad board participant/Consultant: Pfizer; Financial Interests, Personal, Advisory Board, Advisory board participation: Reveal Genomics; Financial Interests, Personal, Advisory Board, Advisory Board Participation: Zymeworks; 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, Steering Committee Member: CytomX. W. Verret: Financial Interests, Institutional, Full or part-time Employment, I am a paid employee of Gilead Sciences: Gilead Sciences. T. Valdez: Financial Interests, Institutional, Stocks/Shares: Gilead Sciences. 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, Coordinating PI: 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. All other authors have declared no conflicts of interest.