TROPiCS-02 Primary Results: Sacituzumab Govitecan versus Treatment of Physician’s Choice in Patients with Advanced Breast Cancer

HR-positive/HER2-negative breast cancer is the most common subtype in patients with metastatic disease. Typically, its treatment includes sequential ET in combination with targeted medicines, followed by single-agent chemotherapy. First-line ET plus a CDK4/6 inhibitor is recommended by international guidelines. The phase 1/2 IMMU-132-01 study included patients with advanced disease and found that average life expectancy was approximately 12 months. SG is a first-in-class Trop-2–directed antibody–drug conjugate approved for metastatic triple-negative breast cancer in patients who have received ≥2 lines of therapy, one being for distant disease. The HR-positive/HER2-negative metastatic breast cancer cohort of the IMMU-132-01 study included 54 SG-treated patients; an overall response rate (ORR) of 31.5% was reported in patients previously exposed to a CDK4/6 inhibitor, along with median progression-free survival (PFS) of 5.5 months, median overall survival (OS) of 12 months, and a manageable safety profile.

TROPiCS-02 included patients with HR-positive/HER2-negative unresectable locally advanced or metastatic breast cancer, an Eastern Cooperative Oncology Group performance status of 0 or 1, and 2 to 4 previous chemotherapy regimens for metastatic breast cancer; 1 prior therapy for metastatic breast cancer was allowed if disease progressed within 12 months of neoadjuvant therapy. Patients were required to have received ≥1 previous taxanes, CDK4/6 inhibitor, and ET. The primary end point was PFS, with OS being a key secondary end point. ORR, duration of response (DOR), clinical benefit rate (CBR), patient-reported outcomes, and safety were additional secondary end points.

Patients were randomly assigned 1:1 to either SG (n = 272) or treatment of physician’s choice (TPC; n = 271). Patients in the SG and TPC arms had similar and well-balanced patient characteristics: 3 median previous chemotherapy regimens for metastatic breast cancer, median age of 56 years, visceral metastases in 95%, history of previous ET in 86%, and previous CDK4/6 inhibitor exposure (60% for ≤12 months and 38% for >12 months). In SG-treated patients versus those receiving TPC, actuarial PFS rates were 46% versus 30% at 6 months and 21% versus 7% at 12 months, respectively, and median PFS was superior with SG versus TPC: 5.5 months versus 4.0 months. Median OS was 13.9 months versus 12.3 months in the SG versus TPC arm, respectively. ORR (21% vs 14%) and CBR (34% vs 22%) were higher with SG versus TPC, whereas median DOR was 7.4 months versus 5.6 months, respectively. The safety profile of SG was similar to that shown in previous studies. Grade 3 treatment-emergent adverse events (TEAEs) were recorded in 74% versus 60% of patients (SG vs TPC); the most common TEAEs were neutropenia (51% vs 39%) and diarrhea (10% vs 1%), respectively. The percentage of adverse events that led to cessation was low in both arms (6% in SG group vs 4% in TPC). In the SG arm, there was 1 treatment-related death, but none in the TPC arm.

In patients with heavily pretreated HR-positive/HER2-negative locally advanced unresectable or metastatic breast cancer who are resistant to ET, SG demonstrated a statistically significant, clinically meaningful PFS benefit over single-agent chemotherapy, with a 34% reduction in risk of the disease progressing or death, along with a manageable safety profile. SG should be considered as a viable and attractive alternative to endocrine monotherapy in appropriate patients with advanced HR-positive/HER2-negative metastatic breast cancer.

Source

Rugo HS, Bardia A, Marmé F, et al. Primary results from TROPiCS-02: a randomized phase 3 study of sacituzumab govitecan (SG) versus treatment of physician’s choice (TPC) in patients (Pts) with hormone receptor–positive/HER2-negative (HR+/HER2-) advanced breast cancer. J Clin Oncol. 2022;40:17. Abstract LBA1001.