FDA Grants Priority Review to Sacituzumab Govitecan for Pretreated HR+/HER2- Metastatic Breast Cancer

FDA

The FDA has accepted and granted priority review to a supplemental biologics license application (sBLA) for sacituzumab govitecan-hziy (Trodelvy) 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.¹

This sBLA is based on findings from the phase 3 TROPiCS-02 trial (NCT03901339), which met its primary end point of progression-free survival (PFS) and key secondary end point of overall survival (OS) vs physician’s choice of chemotherapy. Patients who received sacituzumab govitecan experienced a median PFS of 5.5 months compared with 4 months for chemotherapy (HR, 0.66; 95% CI: 0.53-0.83; P = .0003). Additionally, the median OS in the experimental and control arms was 14.4 months and 11.2 months, respectively (HR, 0.789; 95% CI: 0.646-0.964; P = .02).

The regulatory agency is scheduled to decide on the sBLA by February 2023 under the Prescription Drug User Fee Act.

“[Sacituzumab govitecan] has already changed the treatment landscape in second-line metastatic triple-negative breast cancer [TNBC] and pretreated metastatic urothelial cancer, and today’s news marks our third supplemental application acceptance within the past 2 years,” Bill Grossman, MD, PhD, senior vice president and therapeutic area head of Gilead Oncology, stated in a press release.

“People with pre-treated hormone receptor–positive/HER2-negative metastatic breast cancer who have progressed on endocrine-based therapies and chemotherapy have limited treatment options, and we look forward to working with the FDA to potentially make [sacituzumab govitecan] available to patients who need it most.”

In April 2021, the FDA granted regular approval to sacituzumab govitecan for the treatment of patients with unresectable locally advanced or metastatic TNBC who have previously received 2 or more systemic therapies, at least 1 of them for metastatic disease.² Later in April 2021, the regulatory agency granted accelerated approval to the agent for the treatment of patients with locally advanced or metastatic urothelial cancer who previously received a platinum-containing chemotherapy and either a PD-1 or PD-L1 inhibitor.³

The global, multicenter, open-label TROPiCS-02 trial enrolled 543 patients with hormone receptor–positive/HER2-negative metastatic breast cancer who were previously treated with endocrine therapy, CDK4/6 inhibitors, and 2 to 4 lines of chemotherapy for metastatic disease. Patients were also required to be eligible for one of the chemotherapy options in the physician’s choice arm, have documented disease progression after the most recent therapy, and have adequate bone marrow, renal, and hepatic function.⁴

Key exclusion criteria included previous treatment with topoisomerase I inhibitors as a free form or as other formulations; a history of significant cardiovascular disease or clinically significant electrocardiogram abnormality; Gilbert's disease; or active serious infection requiring antibiotics.

Enrolled patients were randomly assigned 1:1 to 10 mg/kg of intravenous sacituzumab govitecan on day 1 and day 8 of each 21-day cycle, or physician’s choice of chemotherapy consisting of eribulin (Halaven), capecitabine, gemcitabine, or vinorelbine.

Along with the primary end point of PFS assessed by blinded independent central review per RECIST v1.1 criteria and the key secondary end point of OS, other secondary end points included objective response rate (ORR), duration of response (DOR), clinical benefit rate (CBR), quality of life (QOL), and safety.

Additional data presented at the 2022 ESMO Congress showed that sacituzumab govitecan elicited an ORR of 21%, compared with 14% for chemotherapy (odds ratio [OR], 1.63; 95% CI, 1.03-2.56; P = .035).⁵ Additionally, sacituzumab govitecan produced a CBR of 34% vs 22% for chemotherapy (OR, 1.8; 95% CI, 1.23-2.63; P = .003).

Patients treated with sacituzumab govitecan achieved a median DOR of 8.1 months (95% CI, 6.7-9.1). The median DOR was 5.6 months (95% CI, 3.8-7.9) for those who received chemotherapy

Regarding QOL, the median time to deterioration of global health status/QOL was 4.3 months and 3 months for sacituzumab govitecan and chemotherapy, 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 in favor of the experimental agent (HR, 0.73; 95% CI, 0.60-0.89; P = .002).

Safety data were consistent with previously reported findings for sacituzumab govitecan. Treatment-emergent adverse effects leading to discontinuation occurred in 6% of patients in the sacituzumab govitecan arm vs 4% in the chemotherapy arm. TEAEs led to 6 deaths in the sacituzumab govitecan group, compared with no deaths in the chemotherapy group.

References

1. U.S. FDA accepts for priority review the supplemental biologics license application for Gilead’s Trodelvy® for pre-treated HR+/HER2- metastatic breast cancer. News release. Gilead. October 11, 2022. Accessed October 11, 2022. https://bit.ly/3MpnsU1
2. FDA grants regular approval to sacituzumab govitecan for triple-negative breast cancer. News release. FDA. April 7, 2021. Accessed October 11, 2022. https://bit.ly/3fOWhUD
3. FDA grants accelerated approval to sacituzumab govitecan for advanced urothelial cancer. News release. FDA. April 13, 2021. Accessed October 11, 2022. https://bit.ly/3tgxmgy
4. Study of sacituzumab govitecan-hziy versus treatment of physician's choice in participants with HR+/HER2- metastatic breast cancer (TROPiCS-02). ClinicalTrials.gov. Updated May 5, 2022. Accessed October 11, 2022. https://clinicaltrials.gov/ct2/show/NCT03901339
5. 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