20 Final Overall Survival (OS) Analysis From the Phase 3 TROPiCS-02 Study of Sacituzumab Govitecan (SG) in Patients (pts) With Hormone Receptor–Positive/HER2-Negative (HR+/HER2–) Metastatic Breast Cancer (mBC)

20 Final Overall Survival (OS) Analysis From the Phase 3 TROPiCS-02 Study of Sacituzumab Govitecan (SG) in Patients (pts) With Hormone Receptor–Positive/HER2-Negative (HR+/HER2–) Metastatic Breast Cancer (mBC)

Background

Traditional hormone receptor–positive (HR+)/HER2-negative metastatic breast cancer (mBC) treatment is associated with poor outcomes and quality of life. Sacituzumab govitecan is a Trop-2–directed antibody-drug conjugate approved in the United States for patients with metastatic triple-negative breast cancer who received 1 or more prior systemic therapies and for patients with pretreated HR+/HER2-negative mBC. In the phase 3 TROPiCS-02 study, sacituzumab govitecan demonstrated a statistically significant overall survival (OS) benefit vs treatment of physician’s choice (TPC) in patients with pretreated, ET-resistant HR+/HER2-negative mBC at the second planned interim OS analysis with 390 events (median, 14.4 vs 11.2 months; HR, 0.79 [95% CI, 0.65-0.96]; P = .02) this is considered the final analysis per the protocol. Here, we report the results of an exploratory analysis of OS from TROPiCS-02 with a longer median follow-up (12.75 months).

Methods

Eligible patients with HR+/HER2-negative mBC who received prior taxane, ET, CDK4/6 inhibitor, and 2 to 4 prior lines of chemotherapy were randomly assigned 1:1 to receive sacituzumab govitecan (10 mg/kg intravenously on days 1 and 8, every 21 days) or TPC until disease progression or unacceptable toxicity. The primary end point was progression-free survival by blinded independent central review per RECIST v1.1. Key secondary end points included OS and safety. An exploratory analysis evaluated OS by HER2 immunohistochemistry (IHC).

Results

A total of 543 patients (median prior chemotherapy for mBC, 3; visceral metastases, 95%) were randomized to receive sacituzumab govitecan (n = 272) or TPC (n = 271). At data cutoff (December 1, 2022), 437 OS events had occurred, with 47 (8.7%) new deaths in the sacituzumab govitecan vs TPC groups (22 [8.1%] vs 25 [9.2%]) since the second planned interim analysis. Sacituzumab govitecan continues to demonstrate improved OS vs TPC (median, 14.5 vs 11.2 months; HR, 0.79 [95% CI, 0.65-0.95]; nominal P = .01). The OS rates for sacituzumab govitecan vs TPC were 60.9% (95% CI, 54.8-66.4) and 47.1% (95% CI, 41.0-53.0) at 12 months, 39.2% (95% CI, 33.4-45.0) and 31.7% (95% CI, 26.2-37.4) at 18 months, and 25.6% (95% CI, 20.4-31.1) and 21.1% (95% CI, 16.3-26.3) at 24 months. Ninety-two percent of patients were evaluable for HER2 status by immunohistochemistry (IHC) (HER2 IHC 0, n = 217; HER2-low, n = 283). Sacituzumab govitecan demonstrated improved OS vs TPC in the HER2 IHC 0 (median, 13.6 vs 10.8 months; HR, 0.86 [95% CI, 0.63-1.13]) and HER2-low (median, 15.4 vs 11.5 months, HR, 0.74 [95% CI, 0.57-0.97) groups. Updated safety will be reported in the presentation.

Conclusions

This TROPiCS-02 analysis confirms the clinically meaningful OS benefit of sacituzumab govitecan over single-agent chemotherapy in patients with pretreated, endocrine-resistant HR+/HER2-negative mBC. This improvement was independent of HER2-low status. This analysis reinforces sacituzumab govitecan as an effective and safe treatment for this
patient population.