As reported in the Journal of Clinical Oncology by Hope S. Rugo, MD, FASCO, and colleagues, the phase III TROPiCS-02 trial has shown a significant progression-free survival benefit with sacituzumab govitecan-hziy vs chemotherapy in previously treated patients with hormone receptor (HR)-positive, HER2-negative endocrine-resistant advanced breast cancer.

Hope S. Rugo, MD, FASCO

Study Details

The open-label trial included 543 patients with locally advanced inoperable or metastatic disease from sites in the United States, Canada, and Europe. They were randomly assigned between May 2019 and April 2021 to receive sacituzumab govitecan at 10 mg/kg once weekly on days 1 and 8 every 21 days (n = 272) or physician’s choice of single-agent chemotherapy selected prior to random assigment (n = 271). Chemotherapy options were eribulin (48% of patients), vinorelbine (23%), gemcitabine (21%), or capecitabine (8%). Overall, 95% of patients in each group had visceral metastases at baseline. Patients had received a median of three prior lines of chemotherapy in the metastatic setting. The primary endpoint was progression-free survival on blinded independent central review.

Progression-Free Survival

At data cutoff, median duration of follow-up was 10.2 months (11.3 months in the sacituzumab govitecan group and 9.8 months in the chemotherapy group). Median progression-free survival was 5.5 months (95% confidence interval [CI] = 4.2–7.0 months) in the sacituzumab govitecan group vs 4.0 months (95% CI = 3.1–4.4 months) in the chemotherapy group (hazard ratio [HR] = 0.66, 95% CI = 0.53–0.83, P = .0003). Rates at 6 and 12 months were 46% (95% CI = 39%–53%) vs 30% (95% CI = 24%–37%) and 21% (95% CI = 15%–28%) vs 7% (95% CI = 3%–14%).

At first interim analysis, overall survival data were not mature. Median overall survival was 13.9 months (95% CI = 12.7–15.4 months) in the sacituzumab govitecan group and 12.3 months (95% CI = 10.8–14.2) in the chemotherapy group (HR = 0.84, 95% CI = 0.67–1.06, P =.14).

Objective response was observed in 21% (complete response in 1%) vs 14% of patients (all partial responses). The clinical benefit rate was 34% vs 22%. Median duration of response was 7.4 months (95% CI = 6.5–8.6 months) vs 5.6 months (95% CI = 3.8–7.9 months).

Adverse Events

The most common grade ≥ 3 treatment-related adverse events in the sacituzumab govitecan group were neutropenia (51% vs 38% in chemotherapy group), leukopenia (9% vs 5%), diarrhea (9% vs 1%), anemia (6% vs 3%), and fatigue (6% vs 2%). Treatment-related febrile neutropenia occurred in 5% vs 4% of patients. Any-grade interstitial lung disease occurred in 0% vs 1% and any-grade neuropathy was reported in 9% vs 15%. Serious treatment-related adverse events occurred in 14% vs 10% of patients, with the most common in the sacituzumab govitecan group being diarrhea (5%), febrile neutropenia (4%), neutropenia (3%), and neutropenic colitis (2%). Adverse events led to death in six patients in the sacituzumab govitecan group, with one death due septic shock from neutropenic colitis considered related to treatment. No deaths due to adverse events were observed in the chemotherapy group.

The investigators concluded, “Sacituzumab govitecan demonstrated [a] statistically significant progression-free survival benefit over chemotherapy, with a manageable safety profile in patients with heavily pretreated, endocrine-resistant HR-positive/HER2-negative advanced breast cancer and limited treatment options.”

Dr. Rugo, of the University of California San Francisco Helen Diller Family Comprehensive Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Gilead Sciences Inc. For full disclosures of the study authors, visit ascopubs.org.