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Sacituzumab govitecan generated statistically significant and clinically meaningful benefits in overall survival and responses vs physician’s choice of treatment in pretreated patients with hormone receptor–positive, HER2-negative metastatic breast cancer who were resistant to endocrine therapy.
Sacituzumab govitecan-hziy (Trodelvy) generated statistically significant and clinically meaningful benefits in overall survival (OS) and responses vs physician’s choice of treatment in pretreated patients with hormone receptor (HR)–positive, HER2-negative metastatic breast cancer who were resistant to endocrine therapy, according to the second interim analysis of the phase 3 TROPiCS-02 trial (NCT03901339).
Results presented at the 2022 ESMO Congress showed that sacituzumab govitecan elicited a median OS of 14.4 months, compared with 11.2 months with treatment of physician’s choice (HR, 0.79; 95% CI, 0.65-0.96; P = .02). This represents a 3.2-month improvement in survival and a 21% relative reduction in the risk for death.
“This statistically significant and clinically meaningful benefit of sacituzumab [govitecan] over [treatment of physician’s choice] from the TROPiCS-02 study supports the use of sacituzumab [govitecan] as a novel therapy for patients with pretreated, endocrine resistant HR+/HER2- metastatic breast cancer,” Hope S. Rugo, MD, director of Breast Oncology and Clinical Trials Education and professor of medicine in the Division of Hematology and Oncology at the University of California San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center, said during the presentation.
Currently, international guidelines recommend sequential endocrine therapy combined with targeted agents for this patient population; however, optimal sequencing of therapy following endocrine resistance remains unclear, Rugo said during the presentation. For patients who are resistant to endocrine therapy, Sequential single-agent chemotherapy is the standard of care for patients with endocrine-resistant disease, although this treatment is associated with declining efficacy and increasing toxicity.
“With this in mind, there remains a high unmet clinical need for novel, effective therapy options for patients with pretreated HR+/HER2- metastatic breast cancer in the late-line setting,” she continued.
The TROPiCS-02 trial included 543 patients who were previously treated with taxane, endocrine therapy, CDK4/6 inhibitor and 2 to 4 prior lines of chemotherapy. Patients were randomized 1:1 to receive either sacituzumab govitecan (10 mg/kg on days 1 and 8 every 21 days; n = 272) or treatment of physician’s choice (n = 271) until progression or unacceptable toxicity. Follow-up was conducted at a median of 12.5 months.
OS improvements were consistent across most subgroups, including patients who had received 3 or more chemotherapy regimens for metastatic disease and those who received endocrine therapy in the metastatic setting for at least 6 months.
The objective response rate was greater in the sacituzumab govitecan group compared with the treatment of physician’s choice group (21% vs 14%; OR, 1.63; 95% CI, 1.03-2.56; P = .035). The clinical benefit rate was 34% for patients assigned sacituzumab govitecan and 22% for those assigned treatment of physician’s choice (OR, 1.8; 95% CI, 1.23-2.63; P = .003).
Median duration of response was prolonged at 8.1 months (95% CI, 6.7-9.1) with sacituzumab govitecan compared to treatment of physician’s choice at 5.6 months (95% CI, 3.8-7.9).
There was also a significant improvement in quality of life with sacituzumab govitecan compared to treatment of physician’s choice. In particular, the median time to deterioration of global health status/quality of life was 4.3 months and 3 months, respectively (HR, 0.75; 95% CI, 0.61-0.92; P = .006). The median time to deterioration for fatigue was 2.2 months compared with 1.4 months (HR, 0.73; 95% CI, 0.60-0.89; P = .002). Further data on patient-reported outcomes from the TROPiCS-02 study will be presented at the conference.
Safety signals were consistent with past data. In addition, treatment-emergent adverse events leading to discontinuation was “generally low,” Rugo reported, with rates of 6% in the sacituzumab govitecan arm and 4% with treatment of physician’s choice arm. There were 6 deaths due to treatment-emergent adverse events in the sacituzumab govitecan group compared with no deaths in the treatment of physician’s choice group.
Of note, findings from earlier reports of the TROPiCS-02 study demonstrated an improved progression-free survival with sacituzumab govitecan at a median of 5.5 months vs 4.0 months with treatment of physician’s choice (HR, 0.66; 95% CI, 0.53-0.83; P = .0003).
Rugo HS, Bardia A, Marme F, et al. Overall survival (OS) results from the phase III TROPiCS-02 study of sacituzumab govitecan (SG) vs treatment of physician's choice (TPC) in patients (pts) with HR+/HER2- metastatic breast cancer (mBC). Annal Oncol. 2022;33(suppl 7):LBA76. Ddoi:10.1016/annonc/annonc1089