LBA76 - Overall survival (OS) results 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

Pts with HR+/HER2- mBC are treated with endocrine-based therapy (ET), followed by single-agent chemotherapy (CT), with increasingly shorter durations of benefit. SG is an anti–Trop-2 antibody-drug conjugate approved for triple-negative mBC with ≥2 prior therapies (≥1 in the metastatic setting). In TROPiCS-02 (NCT03901339), SG showed significant progression-free survival (PFS) benefit vs TPC in ET resistant HR+/HER2- mBC (HR, 0.66; P<0.001; median 5.5 vs 4.0 mo; Rugo, et al. ASCO 2022). Here, we report the planned TROPiCS-02 OS 2nd interim analysis.

Methods

Eligible pts with HR+/HER2- mBC who received prior taxane, ET, CDK4/6 inhibitor, and 2-4 prior CTs were randomized 1:1 to receive SG (10 mg/kg IV d1 and 8, every 21d) or TPC until progression or unacceptable toxicity. Primary endpoint was PFS by BICR with key secondary endpoint of OS. Per protocol, OS was analyzed after ∼350 events. In the statistical testing hierarchy, objective response rate (ORR) and pt-reported outcomes are tested sequentially if OS is significant.

Results

In total, 543 pts were randomized to receive SG (n=272) vs TPC (n=271). Pts had a median of 3 prior CTs for mBC; 95% had visceral metastases. At data cut-off on July 1, 2022 (median follow-up,12.5 mo), 390 OS events occurred. SG significantly improved OS (median 14.4 vs 11.2 mo; HR, 0.79; P=0.020), ORR, global health status/QoL, and fatigue vs TPC (Table). Safety of SG was consistent with prior reports with no new safety signals identified. Table: 000LBA76

^aAssessed by EORTC QLQ-C30DOR, duration of response; TTD, time-to-deterioration.

Conclusions

SG demonstrated statistically significant and clinically meaningful improvement in OS, and significant improvement in ORR and QoL vs TPC with manageable safety in pts with ET-resistant HR+/HER2- mBC, a population with limited treatment options. These data support the use of SG as a novel therapy for pts with pre-treated HR+/HER2- mBC.

Clinical trial identification

NCT03901339.

Editorial acknowledgement

Shala Thomas from Team Sciences provided editorial support.

Legal entity responsible for the study

Gilead Sciences, Inc.

Funding

Gilead Sciences, Inc.

Disclosure

H.S. Rugo: Financial Interests, Institutional, Other, Honoraria: Puma Biotechnology, Mylan, Samsung BioepisBioepis; Financial Interests, Institutional, Research Grant: 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, Institutional, Research Grant: Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health/Menarini, Immunomedics/Gilead, Daiichi Pharma/Astra Zeneca, Eli Lilly].; Financial Interests, Institutional, Other, Consulting Fees: Pfizer, Novartis, Genentech, Merck, Radius Health/Menarini, Immunomedics/Gilead, Sanofi, Daiichi Pharma/Astra Zeneca, Phillips, Eli Lilly, Foundation Medicine]. F. Marmé: Financial Interests, Institutional, Research Grant: Roche, Novartis, AstraZeneca, GSK/Tesaro, MED, Clovis, Vaccibody, Gilead Sciences, Eisai; Financial Interests, Personal, Other, Consulting Fees: AstraZeneca, TESARO/GSK, Pfizer, EISAI, Gilead, GenomicHealth; Financial Interests, Institutional, Other, Consulting Fees: VACIIBODY; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Clovis, GSK/