Sacituzumab Govitecan Wins Approval in Europe for Pretreated HR+/HER2– Metastatic Breast Cancer

The European Commission has approved sacituzumab govitecan-hziy (Trodelvy) for the treatment of adult patients with unresectable or metastatic hormone receptor–positive, HER2-negative breast cancer who have received endocrine-based therapy and at least 2 additional systemic therapies in the advanced setting.¹

The approval is supported by findings from the phase 3 TROPiCS-02 trial (NCT03901339), which demonstrated that sacituzumab govitecan elicited a statistically significant and clinically meaningful improvement in overall survival (OS) compared with physician’s choice of chemotherapy (HR, 0.789; 95% CI, 0.646-0.964; P = .02). Patients treated with the antibody-drug conjugate (ADC; n = 272) experienced a median OS of 14.4 months (95% CI, 13.0-15.7) compared with 11.2 months (95% CI, 10.1-12.7) in those given chemotherapy (n = 271).²

Additionally, treatment with sacituzumab govitecan led to a 34% reduction in the risk of disease progression or death vs chemotherapy (HR; 0.661; 95% CI, 0.529-0.826; P = .0003).1,2 The median progression-free survival (PFS) was 5.5 months (95% CI, 4.2-7.0) with sacituzumab govitecan compared with 4.0 months (95% CI, 3.1-4.4) with chemotherapy.² Notably, the 1-year PFS rate was 21% in the experimental arm vs 7% in the control arm.¹

"The European approval of sacituzumab govitecan is an important milestone for the European breast cancer community,” Javier Cortes, MD, PhD, head of the International Breast Cancer Center in Madrid and Barcelona, Spain, stated in a news release. “We now have a new treatment option that has delivered a proven and clinically meaningful survival benefit for women in Europe with pretreated hormone receptor–positive/HER2-negative metastatic breast cancer.”

In February 2023, the FDA approved sacituzumab govitecan for the treatment of adult patients with unresectable locally advanced or metastatic hormone receptor–positive, HER2-negative breast cancer who have received endocrine-based therapy and at least 2 additional systemic therapies in the metastatic setting.² This approval was also based on data from TROPiCS-02.

TROPiCS-02 was a global, multicenter, open-label trial that enrolled patients with hormone receptor–positive, HER2-negative metastatic breast cancer who were previously treated with endocrine therapy, a CDK4/6 inhibitor, and 2 to 4 lines of chemotherapy for metastatic disease.

During the study, 543 patients were randomly assigned to receive intravenous sacituzumab govitecan at 10 mg/kg on days 1 and 8 of each 21-day cycle, or physician's choice of single-agent chemotherapy with eribulin, capecitabine, gemcitabine, or vinorelbine.

The primary end point was PFS assessed by blinded independent central review per RECIST v1.1 criteria. Secondary end points included OS, overall response rate (ORR), clinical benefit rate (CBR), duration of response (DOR), quality of life, safety, and tolerability.¹

Further data presented at the 2022 ESMO Congress demonstrated that patients treated with the ADC experienced an ORR of 21% vs 14% in those given chemotherapy (odds ratio [OR], 1.63; 95% CI, 1.03-2.56; P = .035).3 The CBRs in the sacituzumab govitecan and chemotherapy arms were 34% and 22%, respectively (OR, 1.8; 95% CI, 1.23-2.63; P = .003).

The median DOR was 8.1 months (95% CI, 6.7-9.1) with sacituzumab govitecan vs 5.6 months (95% CI, 3.8-7.9) with chemotherapy.

Regarding safety, data from TROPiCS-02 were consistent with prior studies of sacituzumab govitecan. No new safety signals were identified in this patient population. The most frequent serious adverse effects (AEs) reported in more than 1% of patients included diarrhea (5%), febrile neutropenia (4%), neutropenia (3%), abdominal pain (2%), colitis (2%), neutropenic colitis (2%), pneumonia (2%), and vomiting (2%).¹

Six percent of patients in the experimental arm discontinued sacituzumab govitecan due to AEs compared with 4% of patients given chemotherapy.³

References

1. European Commission approves Gilead’s Trodelvy® for pre-treated HR+/HER2- metastatic breast cancer. News release. Gilead. July 27, 2023. Accessed July 27, 2023. https://investors.gilead.com/news/news-details/2023/European-Commission-Approves-Gileads-Trodelvy-For-Pre-Treated-HRHER2--Metastatic-Breast-Cancer/default.aspx
2. FDA approves sacituzumab govitecan-hziy for HR-positive breast cancer. News release. FDA. February 3, 2023. Accessed July 28, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-sacituzumab-govitecan-hziy-hr-positive-breast-cancer
3. 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). Ann Oncol. 2022;33(suppl 7):S1386. doi:10.1016/j.annonc.2022.08.012