Updated findings from the phase 3 TROPiCS-02 trial support sacituzumab govitecan as a standard treatment for hormone receptor–positive, HER2-negative breast cancer, according to Sara Tolaney, MD, MPH.
Investigators observed a statistically significant improvement in overall survival (OS) following treatment with sacituzumab govitecan-hziy (Trodelvy) compared with chemotherapy in patients with hormone receptor (HR)–positive, HER2-negative metastatic breast cancer, according to findings from the final OS analysis of the phase 3 TROPiCS-02 trial (NCT03901339).1
The median OS was 14.4 months (95% CI, 13.0-15.7) in the sacituzumab govitecan arm vs 11.2 months (95% CI, 10.1-12.7) in the chemotherapy arm (HR, 0.79; 95% CI, 0.65-0.96; P = .020). In each respective arm, investigators reported OS rates of 61% (95% CI, 55%-66%) vs 47% (95% CI, 41%-53%) at 12 months, 39% (95% CI, 33%-45%) vs 32% (95% CI, 27%-38%) at 18 months, and 25% (95% CI, 19%-31%) vs 21% (95% CI, 16%-27%) at 24 months. OS benefits with sacituzumab govitecan extended across patient subgroups, which included those who received at least 3 prior lines of chemotherapy in the metastatic setting, those with visceral metastases, and those treated with endocrine therapy for at least 6 months in the metastatic setting.
Investigators noted that sacituzumab govitecan produced an OS benefit regardless of patient Trop-2 expression. The median OS among those with an H-score of less than 100 was 14.6 months with sacituzumab govitecan vs 11.3 months with chemotherapy. Additionally, the median OS in each respective treatment arm was 14.4 months vs 11.2 months among patients with an H-score of 100 or higher.
“These data reinforce that sacituzumab govitecan is leading to improvements in both progression-free survival [PFS] and [OS] and that patients saw benefit irrespective of their tumor’s Trop-2 expression,” senior author Sara M. Tolaney, MD, MPH, chief of the Division of Breast Oncology at the Susan F. Smith Center for Women’s Cancers at Dana-Farber Cancer Institute, said in a press release on these findings.2 “This updated analysis continues to support sacituzumab govitecan as a standard treatment for patients with pretreated, endocrine-resistant [HR-positive/HER2-negative] metastatic breast cancer.”
Investigators of the international, multi-center phase 3 TROPiCS-02 trial assessed sacituzumab govitecan compared with physician’s choice of chemotherapy in patients with locally recurrent, metastatic, HR-positive, HER2-negative breast cancer. Patients were randomly assigned 1:1 to receive 10 mg/kg of sacituzumab govitecan intravenously on day 1 and 8 of every 21-day cycle or single-agent chemotherapy, which included the options of eribulin, capecitabine, gemcitabine, and vinorelbine.
The trial’s primary end point was PFS per blinded independent central review based on RECIST v1.1 criteria. Secondary end points included OS, objective response rate (ORR), and patient-reported outcomes.
Patients 18 years and older who received at least 1 previous endocrine therapy, a taxane, and a CDK4/6 inhibitor in any setting plus 2 to 4 lines of chemotherapy were eligible for enrollment on the trial. Patients also needed to have an ECOG performance status of 0 or 1 and at least 1 measurable lesion per RECIST v1.1 criteria.
The trial population included 268 patients who received sacituzumab govitecan and 249 who received chemotherapy. The median patient age was 56 years (interquartile range [IQR], 49-65), and the median number of prior chemotherapy lines for advanced disease was 3 (IQR, 2-3). Investigators noted that patient demographics and characteristics were comparable between treatment arms.
The ORR was 21% in the sacituzumab govitecan arm, which included a partial response (PR) rate of 20% and a complete response (CR) rate of 1%. The ORR in the chemotherapy arm was 14%, which consisted entirely of PRs. The median duration of response was 8.1 months (95% CI, 6.7-9.1) in the experimental arm vs 5.6 months (95% CI, 3.8-7.9) in the chemotherapy arm.
The median time to deterioration for global health status or quality of life was 4.3 months with sacituzumab govitecan vs 3.0 months with chemotherapy (HR, 0.75; 95% CI, 0.61-0.92; P = .0059). Additionally, the median time to deterioration for fatigue was 2.2 months vs 1.4 months (HR, 0.73; 95% CI, 0.60-0.89; P = .0021), and the median time to deterioration for pain was 3.8 months vs 3.5 months (HR, 0.92; 95% CI, 0.75-1.13; P = .42) in each respective treatment arm.
The most common any-grade treatment-emergent adverse effects (TEAEs) in the sacituzumab govitecan and chemotherapy arms, respectively, included neutropenia (71% vs 55%), diarrhea (62% vs 23%), nausea (59% vs 35%), alopecia (48% vs 18%), and anemia (37% vs 28%). Grade 3 or higher TEAEs in each arm included neutropenia (51% vs 39%) and diarrhea (10% vs 1%).
Overall, 6% and 4% of patients in the sacituzumab govitecan and chemotherapy arms, respectively, discontinued treatment due to AEs. Investigators observed 6 fatal AEs in the sacituzumab govitecan arm, 1 of which was attributed to septic shock resulting from neutropenic colitis.