Sacituzumab Govitecan-hziy Significantly Improves Overall Survival in HR+/HER2- Metastatic Breast Cancer vs Chemotherapy

Gilead Sciences Inc submitted a supplemental Biologics License Application to the FDA for sacituzumab govitecan-hziy (Trodelvy) following promising trial results.

Treatment with sacituzumab govitecan-hziy (Trodelvy, Gilead Sciences Inc) provided clinically significant and meaningful results in improved overall survival (OS) in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer who were previously treated with endocrine therapy, CDK4/6 inhibitors, and 2 to 4 lines of chemotherapy.

These results were from a second interim analysis of the phase 3 TROPiCS-02 study of sacituzumab govitecan-hziy in 543 patients (HER2-low or IHC 0 status).

“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,” said Merdad Parsey, MD, PhD, chief medical officer, Gilead Sciences, in a press release.

The primary endpoint of the trial is progression-free survival for patients taking sacituzumab govitecan-hziy, as assessed by a blinded independent central review (BICR). Secondary endpoints include OS, overall response rate (ORR), clinical benefit rate, duration of response, and assessment of safety, tolerability, and quality of life measures.

TROPiCS-02 is a global, multicenter, open-label, randomized 1:1 phase 3 trial evaluating sacituzumab govitecan-hziy vs physician-prescribed chemotherapy for patients with HR+/HER2- metastatic breast cancer.

HR+/HER2- breast cancer accounts for 70% of all breast cancer cases. Approximately 400,000 people each year are diagnosed worldwide and approximately 33% of all early-stage breast cancers will spread to other parts of the body. The 5-year relative survival rate for these patients hovers at 30%.

Endocrine-based therapy is the first line of defense for HR+/HER2- metastatic breast cancer. If the cancer persists, individuals receive single-agent chemotherapy. Patients will typically receive multiple rounds of chemotherapy, although it has a low success rate.

Sacituzumab govitecan-hziy is a conjugated Trop-2-directed antibody and topoisomerase inhibitor that was previously approved for the treatment of patients with triple-negative breast cancer administered 2 prior therapies at minimum for metastatic disease. The FDA also granted accelerated approval to sacituzumab govitecan-hziy in April 2021 based on duration and level of tumor response for the treatment of patients with locally advanced or metastatic urothelial cancer who previously received a platinum-containing chemotherapy and either a programmed cell death protein 1 or programmed death-ligand 1 inhibitor.

This drug is approved in more than 35 countries to treat adults with unresectable locally advanced or metastatic triple-negative breast cancer who were previously treated for metastatic disease. In the United States, trials such as TROPiCS-02 are investigating sacituzumab govitecan-hziy to treat HR+/HER2- metastatic breast cancer.

Other trials are researching sacituzumab govitecan-hziy for metastatic non-small cell lung cancer, metastatic small cell lung cancer, head and neck cancer, and endometrial cancer.

The most common adverse effects (AEs) of treatment with sacituzumab govitecan-hziy include severe and life-threatening neutropenia and severe diarrhea.

“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,” Parsey concluded in the press release.

Reference

Gilead Sciences, Inc. Trodelvy Significantly Improves Overall Survival in Pre-Treated HR+/HER2- Metastatic Breast Cancer Patients in the TROPiCS-02 Study. Gilead website. August 15, 2022. Accessed on August 16, 2022. https://www.gilead.com/news-and-press/press-room/press-releases/2022/8/trodelvy-significantly-improves-overall-survival-in-pretreated-hrher2-metastatic-breast-cancer-patients-in-the-tropics02-study