Abstract 193P
Background
TROPiCS-02 (T-02) and EVER-132-002 (E-002) are both phase III randomized controlled trials comparing sacituzumab govitecan (SG) to treatment of physician’s choice (TPC) in patients with HR+/HER2- locally recurrent inoperable or metastatic breast cancer (MBC) who have progressed after 2-4 prior chemotherapy regimens for metastatic disease. T-02, but not E-002, required prior CDK4/6 inhibitor (CDK4/6i) treatment. Here, we explored if efficacy of SG vs TPC would vary in a population with or without prior CDK4/6i treatment via a meta-analysis of the two studies.
Methods
Meta-analytic models were developed to adjust for cross-trial differences while comparing efficacy of SG versus TPC. Individual patient data and study level hazard ratios from T-02 and E-002 were combined to estimate pooled treatment effects for comparison of overall survival (OS) and progression-free survival (PFS) in the overall and CDK4/6i pretreated populations.
Results
In general, T-02 and E-002 had similar distribution of baseline population characteristics (low heterogeneity, I-square = 0.0%-9.6%) except for prior CDK4/6i treatment and geography. In all meta-analytic models SG showed a significant improvement over TPC in OS and PFS. Similar patterns in efficacy were observed in the subgroup of patients previously treated with CDK4/6i (Table). Table: 193P
SG vs TPC comparison of OS and PFS
| Pooled Treatment Effect HR (95% CI) | Overall population | Prior CDK4/6 treated |
| Combined individual patient data | ||
| OS | 0.66 (0.55-0.80); p<0.001 | 0.65 (0.53-0.80); p<0.001 |
| PFS | 0.62 (0.50-0.77); p<0.001 | 0.65 (0.52-0.81); p<0.001 |
| Combined study level hazard ratios | ||
| OS | 0.70 (0.58-0.86); p<0.001 | 0.68 (0.55-0.84); p<0.001 |
| PFS | 0.67 (0.55-0.83); p<0.001 | 0.66 (0.52-0.84); p=0.001 |
Conclusions
SG significantly improves OS and PFS vs. TPC in the meta-analysis of T-02 and E-002 trial in the overall and CDK4/6i pre-treated MBC populations. The results obtained from this analysis are consistent with trial-level results from T-02 and E-002, reinforcing the efficacy benefits of SG over TPC.
Clinical trial identification
NCT03901339, NCT04639986.
Legal entity responsible for the study
Gilead Sciences, Inc.
Funding
Gilead Sciences, Inc.
Disclosure
O. Gluz: Financial Interests, Personal, Advisory Board: Roche, Lilly, Novartis, Pierre Fabre, MSD, Pfizer, Gilead, Seagen, Agendia; Financial Interests, Personal, Invited Speaker: AstraZeneca, Exact Science; Financial Interests, Institutional, Invited Speaker: Roche, LIlly; Non-Financial Interests, Leadership Role: West German Study Group; Non-Financial Interests, Personal, Proprietary Information: West German Study Group. B. Xu: Financial Interests, Personal, Advisory Role: AstraZeneca, Novartis. R. Nanda: Financial Interests, Personal, Advisory Board: AstraZeneca, BeyondSpring, Daiichi Sankyo, Exact Sciences, FujiFilm, GE, Gilead, Guardant Health, Infinity, iTeos, Merck, Moderna, Novartis, OBI, Oncosec, Pfizer, Sanofi, Seagen, Stemline; Financial Interests, Institutional, Invited Speaker: Arvinas, AstraZeneca, Genentech/Roche, Gilead, GSK, Novartis, OBI, OncoSec, Pfizer, Relay, Seagen, Sun Pharma, Taiho; Financial Interests, Institutional, Research Grant: BMS, Corcept Therapeutics, Merck. A. Dasgupta: Financial Interests, Institutional, Full or part-time Employment: Gilead Sciences; Financial Interests, Institutional, Stocks/Shares: Gilead Sciences. A. Kaushik: Financial Interests, Institutional, Full or part-time Employment: Gilead Sciences; Financial Interests, Institutional, Stocks/Shares: Gilead Sciences. W. Verret: Financial Interests, Institutional, Full or part-time Employment, I am a paid employee of Gilead Sciences: Gilead Sciences. A. Sharma: Financial Interests, Institutional, Full or part-time Employment: Pharmacoevidence Private Limited. B. Singh: Financial Interests, Institutional, Member of Board of Directors: Pharmacoevidence Pvt Ltd.; Financial Interests, Institutional, Stocks/Shares: Pharmacoevidence Pvt Ltd.; Non-Financial Interests, Officer: Pharmacoevidence Pvt Ltd. H.S. Rugo: Financial Interests, Personal, Other, Consultancy/advisory support: NAPO, Mylan/Viatris, Daiichi Sankyo, Eisai; Financial Interests, Institutional, Invited Speaker: Novartis, Lilly, Pfizer, OBI Pharma, F. Hoffmann-La Roche AG/Genentech, Inc., Daiichi, AstraZeneca, Gilead Sciences, Inc., Merck; Financial Interests, Institutional, Research Grant: Stemline Therapeutics, Ambryx; Non-Financial Interests, Advisory Role, I advise a number of companies without compensation: Various. All other authors have declared no conflicts of interest.