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.
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.
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
|SG (n=272)||TPC (n=271)|
|Median OS, mo||14.4||11.2|
|HR (95% CI)||0.79 (0.65-0.96), P=0.02|
|ORR, n (%)||57 (21)||38 (14)|
|Odds ratio (95% CI)||1.63 (1.03-2.56), P=0.035|
|Median DOR, mo (95% CI)||8.1 (6.7-9.1)||5.6 (3.8-7.9)|
|TTD of Global Health Score / Quality of Life,a mo||4.3||3.0|
|HR (95% CI)||0.75 (0.61-0.92), P=0.006|
|TTD of Fatigue,a mo||2.2||1.4|
|HR (95% CI)||0.73 (0.60-0.89), P=0.002|
|TTD of Pain,a mo||3.8||3.5|
|HR (95% CI)||0.92 (0.75-1.13), P=0.42|
aAssessed by EORTC QLQ-C30DOR, duration of response; TTD, time-to-deterioration.
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
Shala Thomas from Team Sciences provided editorial support.
Legal entity responsible for the study
Gilead Sciences, Inc.
Gilead Sciences, Inc.
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/