Sacituzumab Govitecan Prolongs OS in Heavily Pretreated HR+ Breast Cancer

Merdad Parsey, MD, PhD

Sacituzumab govitecan-hziy (Trodelvy) elicited a statistically significant and clinically meaningful improvement in overall survival (OS) vs standard chemotherapy in patients with hormone receptor–positive, HER2-negative breast cancer who received prior treatment with endocrine therapy, CDK4/6 inhibitors, and 2 to 4 lines of chemotherapy, according to findings from the second interim analysis of the phase 3 TROPiCS-02 trial (NCT03901339).¹

Additionally, no new safety signals were observed, and the safety profile for sacituzumab govitecan was consistent with prior studies. The detailed OS findings will be presented at an upcoming medical conference.

“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, stated in a news release. “We look forward to discussing these results with global health authorities, as [patients with] pretreated hormone receptor–positive/HER2-negative metastatic disease currently have limited treatment options and poor quality of life.”

Previously in August 2022, the National Comprehensive Cancer Network updated its guidelines regarding use of sacituzumab govitecan in hormone receptor–positive/HER2-negative metastatic breast cancerto a category 2A preferred recommendation.² That decision was based on data from TROPiCS-02 presented at the 2022 ASCO Annual Meeting, which showed that at a median follow-up of 10.2 months, the median progression-free survival (PFS) was 5.5 months (95% CI, 4.2-7.0) for sacituzumab govitecan compared with 4.0 months (95% CI, 3.1-4.4) for physician’s choice of chemotherapy (HR, 0.66; 95% CI, 0.53-0.83; P = .0003).³

The global, multicenter, open-label TROPiCS-02 study evaluated the efficacy and safety of single-agent sacituzumab govitecan vs physician’s choice of chemotherapy in patients with hormone receptor–positive, HER2-negative metastatic breast cancer who were refractory to or relapsed after at least 2 and no more than 4 prior systemic chemotherapy regimens for metastatic disease, including at least 1 anticancer hormonal treatment and at least 1 CDK4/6 inhibitor in the metastatic setting.⁴

Patients were also required to have documented disease progression after their most recent therapy, be eligible for 1 of the chemotherapy options in the physician’s choice arm, and have adequate bone marrow, renal, and hepatic function. Key exclusion criteria included prior treatment with a topoisomerase 1 inhibitor, a history of significant cardiovascular disease or clinically significant electrocardiogram abnormality, Gilbert’s disease, or the presence of an active, serious infection requiring antibiotics. Patients with stage IIIC locally advanced metastatic breast cancer who were candidates for curative intent therapy at the time of study enrollment were not permitted to enroll.

Once enrolled, patients were randomized 1:1 to receive 10 mg/kg of intravenous sacituzumab govitecan on days 1 and 8 of every 21-day cycle or investigator’s choice of therapy. Treatment continued until disease progression or unacceptable toxicity.

The primary end point of the trial was PFS, and secondary end points included OS, overall response rate, duration of response, quality of life, and safety.

In April 2021, the FDA granted regular approval to sacituzumab govitecan for the treatment of patients with unresectable locally advanced or metastatic triple-negative breast cancer who have previously received 2 or more systemic therapies, at least 1 of them for metastatic disease.⁵ Later in April 2021, sacituzumab govitecan also received an accelerated approval from the FDA 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.⁶

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 15, 2022. https://bit.ly/3Aqlj6t
2. Sacituzumab govitecan-hziy (Trodelvy) elevated to category 1 preferred recommendation in second-line metastatic triple-negative breast cancer and added as a category 2a preferred recommendation for HR+/HER2- metastatic breast cancer in NCCN clinical practice guidelines in oncology (NCCN Guidelines). Gilead Sciences. August 3, 2022. Accessed August 15, 2022. https://bit.ly/3bFVlCa
3. Rugo HS, Bardia A, Marmé 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
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 August 15, 2022. https://clinicaltrials.gov/ct2/show/NCT03901339
5. FDA grants regular approval to sacituzumab govitecan for triple-negative breast cancer. News release. FDA. April 7, 2021. Accessed August 15, 2022. https://bit.ly/3fOWhUD
6. FDA grants accelerated approval to sacituzumab govitecan for advanced urothelial cancer. News release. FDA. April 13, 2021. Accessed August 15, 2022. https://bit.ly/3tgxmgy