Sacituzumab Govitecan Yields Significant OS Improvement Vs Physician’s Choice in HR+/HER2– Metastatic Breast Cancer

A statistically significant and clinically meaningful improvement in overall survival (OS) was observed following treatment with sacituzumab govitecan-hziy (Trodelvy) for patients with hormone receptor–positive, HER2-negative metastatic breast cancer who received prior endocrine therapy, CDK4/6 inhibitor, and 2 to 4 lines of chemotherapy, according to a press release from Gilead Sciences on the second interim analysis of the phase 3 TROPiCS-2 trial (NCT03901339).¹

The study’s OS data will be presented at an upcoming conference. Safety remained consistent with previously reported results. Additionally, a supplemental biologics license application has been submitted to the FDA for the indication.

“These survival results from the TROPiCS-02 study are important for the breast cancer community and we are encouraged by the potential this may have in helping patients who otherwise have limited alternatives,” Merdad Parsey, MD, PhD, chief medical officer of Gilead Sciences, said in the press release. “We look forward to discussing these results with global health authorities, as pre-treated HR+/HER2– metastatic disease patients currently have limited treatment options and poor quality of life.”

The study’s primary results were presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting. A total of 543 pre-treated patients were enrolled and randomly assigned 1:1 to either the sacituzumab govitecan arm (n = 271)—receiving 10 mg/kg intravenously on days 1 and 8 of each 21-day cycle—or physician’s choice therapy of either capecitabine (Xeloda), vinorelbine (Navelbine), gemcitabine, or eribulin (Halaven; n = 271).

The primary end point was progression-free survival (PFS) by blinded independent review (BICR), with secondary end points being OS, objective response rate (ORR), duration of response (DOR), and clinical benefit rate by local investigator review and BICR. The median duration of follow-up was 10.2 months.

The median PFS in the sacituzumab govitecan arm was 5.5 months (95% CI, 4.2-7.0) and 4.0 months (95% CI, 3.1-4.4) in the physician’s choice arm (HR, 0.66; 95% CI, 0.53-0.83; P = .0003). At 6 months, the PFS rate was 46.1% (95% CI, 39.4%-52.6%) vs 30.3% (95% CI, 23.6%-37.3%), at 9 months it was 32.5% (95% CI, 25.9%-39.2%) vs 17.3% (95% CI, 11.5%-24.2%), and at 12 months it was 21.3% (95% CI, 15.2%-28.1%) vs 7.1% (95% CI, 2.8%-13.9%) in the sacituzumab govitecan and physician’s choice therapy arms, respectively.

At the time of the presentation, the OS data were not yet mature. The median OS was 13.9 months (95% CI, 12.7-15.4) in the sacituzumab govitecan arm and 12.3 months (95% CI, 10.8-14.2) in the physician’s choice arm (HR, 0.84; 95% CI, 0.67-1.06; P = .14). The ORR was 21.0% vs 14.0% (P = .03), the clinical benefit rate was 34.0% vs 22.0% (P = .002), and the median DOR was 7.4 months (95% CI, 6.5-8.6) vs 5.6 months (95% CI, 3.8-7.9) in the sacituzumab govitecan and physician’s choice therapy arms, respectively.

The safety population consisted of 268 patients in the sacituzumab govitecan arm. Reasons for discontinuation in the cohort included progressive disease (n = 210), adverse effects (AEs; n = 18), consent withdrawal (n = 8), treatment delay by over 3 weeks (n = 5), other reasons (n = 5), death (n = 3), and protocol deviation (n = 1). In total, 18 patients remained on treatment. In the physician’s choice therapy arm, 249 patients were included in the safety population. Reasons for discontinuation included progressive disease (n = 197), consent withdrawal (n = 22), AEs (n = 11), other reasons (n = 6), protocol deviation and COVID-19 (n = 3, respectively), death (n = 2), and treatment delay of more than 3 weeks (n = 1). In this arm, 4 patients remained on treatment.

Grade 3 or higher treatment-emergent AEs (TEAEs) occurred in 74% of those in the sacituzumab govitecan arm vs 60% in the physician’s choice arm. TEAEs leading to discontinuation were observed in 6% vs 4%, 66% vs 44% had a dose delay, and 33% vs 33% had dose reductions in each respective cohort. Serious TEAEs occurred in 28% vs 19% and TEAEs leading to death occurred in 2% vs 0% of those in the sacituzumab govitecan and physician’s choice therapy arms, respectively.

In the sacituzumab govitecan arm, no patients experienced interstitial lung disease vs 1% in the physician’s choice arm, and no treatment-related AEs of cardiac failure or left ventricular dysfunction was observed in either arm.

References

1. Trodelvy significantly improves overall survival in pre-treated HR+/HER2- metastatic breast cancer patients in the TROPiCS-02 study. News Release. Gilead Sciences. August 15, 2022. Accessed August 16, 2022. https://bit.ly/3C9NE28
2. Rugo HS, Bardia A, Marme 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(suppl 17):LBA1001. doi:10.1200/JCO.2022.40.17_suppl.LBA1001