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).
Sara M. Tolaney, Aditya Bardia, Frederik Marmé, Javier Cortés, Peter Schmid, Delphine Loirat, Olivier Trédan, Eva Ciruelos, Florence Dalenc, P. Gómez Pardo, Komal Jhaveri, Rosemary Delaney, T. Valdez, Oh Kyu Yoon, Hao Wang, Wendy Verret, Hope S. Rugo
Abstract
1003 Background: Treatment of HR+/HER2– mBC includes sequential endocrine therapy (ET) combined with targeted agents followed by sequential single-agent chemotherapy (CT), which is associated with poor outcomes and quality of life. SG is a Trop-2–directed antibody-drug conjugate approved in multiple countries for pts with metastatic triple-negative breast cancer who received ≥1 prior systemic therapy and in the US for pts with pretreated HR+/HER2- mBC. In the phase 3 TROPiCS-02 study, SG demonstrated a statistically significant OS benefit versus treatment of physician’s choice (TPC) in pts with pretreated, ET-resistant HR+/HER2– mBC at the 2nd planned interim OS analysis with 390 events (median, 14.4 vs 11.2 mo; HR, 0.79 [95% CI, 0.65-0.96]; P=0.02; Rugo HS, et al. ESMO 2022. LBA76); 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 mo). Methods: Eligible pts withHR+/HER2– mBC who received prior taxane, ET, CDK4/6 inhibitor, and 2-4 prior lines of CT were randomly assigned 1:1 to receive SG (10 mg/kg IV d1 and 8, every 21 d) or TPC until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival by blinded independent central review per RECIST v1.1. Key secondary endpoints included OS and safety. In an exploratory analysis, we evaluated OS by HER2 immunohistochemistry (IHC). Results: In total, 543 pts (median prior CT for mBC, 3; visceral metastases, 95%) were randomized to receive SG (n=272) or TPC (n=271). At data cutoff (Dec 1, 2022), 437 OS events had occurred (median follow-up, 12.75 mo), with 47 (8.7%) new deaths in the SG versus TPC groups (22 [8.1%] vs 25 [9.2%]) since the 2nd planned interim analysis. With this extended follow-up, SG continues to demonstrate improved OS versus TPC (median, 14.5 vs 11.2 mo; HR, 0.79 [95% CI, 0.65-0.95]; nominal P=0.01). The OS rates (95% CI) for SG versus TPC were 60.9% (54.8-66.4) and 47.1% (41.0-53.0) at 12 months, 39.2% (33.4-45.0) and 31.7% (26.2-37.4) at 18 months, and 25.6% (20.4-31.1) and 21.1% (16.3-26.3) at 24 months. Overall, 92% of pts were evaluable for HER2 status by IHC (HER2 IHC0, n=217; HER2-low, n=283). SG demonstrated improved OS versus TPC in the HER2 IHC0 (median, 13.6 vs 10.8 mo; HR, 0.86 [95% CI, 0.63-1.13]) and HER2-low (median, 15.4 vs 11.5 mo, HR, 0.74 [95% CI, 0.57-0.97) groups. Updated safety will be reported at the time of presentation. Conclusions: The final OS analysis of the TROPiCS-02 study confirms the clinically meaningful OS benefit of SG over single-agent CT in pts with pretreated, endocrine-resistant HR+/HER2–mBC. This improvement was independent of HER2-low status. This analysis reinforces SG as an effective and safe treatment for this pt population with limited treatment options. Clinical trial information: NCT03901339 .