Primary Results From TROPiCS-02: A Randomized Phase 3 Study of Sacituzumab Govitecan (SG) vs Treatment of Physician’s Choice (TPC) in Patients (Pts) With Hormone Receptor-Positive/HER2-Negative (HR+/HER2-) Advanced Breast Cancer.
Background: HR+/HER2– disease is the most common subtype of metastatic breast cancer (MBC). Treatment includes sequential endocrine therapy combined with targeted agents followed by single-agent chemotherapy, with increasingly shorter durations of benefit. SG is an anti–Trop-2 antibody-drug conjugate approved for metastatic triple-negative breast cancer with ≥2 prior therapies (≥1 for MBC). The HR+/HER2– MBC cohort of the phase 1/2 IMMU-132-01 study (n = 54) had an objective response rate (ORR) of 31.5%, median progression-free survival (PFS) of 5.5 mo, median overall survival (OS) of 12 mo, and a manageable safety profile with SG. TROPiCS-02 is a phase 3 randomized study (NCT03901339) to confirm SG outcomes in HR+/HER2– advanced breast cancer.
Methods: Adults with locally determined, HR+/HER2– unresectable locally advanced or MBC, ECOG performance status of 0 or 1, and 2-4 prior chemotherapy regimens for MBC were eligible; 1 prior therapy for MBC was allowed if disease progressed ≤12 mo after (neo)adjuvant therapy. Pts must have received ≥1 prior taxane, CDK4/6 inhibitor, and endocrine therapy in any setting. Pts were randomized 1:1 to receive SG (10 mg/kg IV on d1 and 8, every 21d) or TPC (capecitabine, eribulin, vinorelbine, or gemcitabine) until disease progression/unacceptable toxicity. Primary endpoint was PFS per RECIST v1.1 by blinded independent central review (final analysis) with key secondary endpoint of OS (1st planned interim analysis).
Results: At data cutoff on Jan 3, 2022, 272 vs 271 pts were randomized to receive SG vs TPC, respectively. Pt characteristics in the SG vs TPC arms were similar (3 median prior chemotherapy regimens for MBC [range, 0-8]; 95% had visceral metastases, 86% had prior endocrine therapy for MBC for ≥6 mo, 60% and 38% received prior CDK4/6 inhibitors for ≤12 and > 12 mo, respectively). SG (vs TPC) improved median PFS (5.5 vs 4.0 mo; HR, 0.66; 95% CI, 0.53-0.83; P= 0.0003); PFS rates at 6 and 12 mo were 46% vs 30% and 21% vs 7%, respectively. SG vs TPC showed a numeric but nonsignificant difference in OS (13.9 vs 12.3 mo; HR, 0.84; P= 0.143); ORR (21% vs 14%) and clinical benefit rate (34% vs 22%) were higher with SG vs TPC and median duration of response was 7.4 vs 5.6 mo, respectively. Overall, 74% vs 60% of patients (SG vs TPC) had grade ≥3 treatment-emergent adverse events (AEs); neutropenia (51% vs 39%) and diarrhea (10% vs 1%) were most common. AEs leading to discontinuation of SG vs TPC were low (6% vs 4%). There was 1 treatment-related death in the SG arm; none in the TPC arm.
Conclusions: SG had a statistically significant, clinically meaningful PFS benefit over single-agent chemotherapy and a manageable safety profile in pts with heavily pre-treated HR+/HER2– endocrine-resistant, unresectable locally advanced or MBC, who have limited treatment options.
Research Sponsor: Gilead Sciences, Inc.