FDA Approves Sacituzumab Govitecan for Unresectable, Advanced HR+/HER2- Breast Cancer

The FDA has granted approval to sacituzumab govitecan-hziy (Trodelvy) for the treatment of adult patients with unresectable locally advanced or metastatic hormone receptor (HR)-positive, HER2-negative (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting.¹

The approval comes on the heels of impressive data presented at the San Antonio Breast Cancer Symposium, which come from the phase 3 TROPiCS-02 study (NCT03901339). In TROPiCS-02, sacituzumab govitecan was compared with standard-of-care chemotherapy of physicians’ choice in patients with HR+/HER2- metastatic breast cancer who progressed on endocrine-based therapies and at least 2 chemotherapies.

Hope S. Rugo, MD

“Despite decades of advances, people living with pre-treated HR+/HER2- metastatic breast cancer need new treatment options. Nearly all people with this type of breast cancer will eventually develop resistance to endocrine-based therapies and progress on available chemotherapies,” said Hope S. Rugo, MD, professor of Medicine and director, Breast Oncology and Clinical Trials Education at the UCSF Helen Diller Family Comprehensive Cancer Center, U.S. and principal investigator of the TROPiCS-02 study, in a press release.

“This approval is significant for the breast cancer community. We have had limited options to offer patients after endocrine-based therapy and chemotherapy, and to see a clinically meaningful survival benefit of more than 3 months with a quality-of-life benefit for these women is exceptional," Rugo added.

TROPiCS-02 included 543 patients who were randomized 1:1 to receive either sacituzumab govitecan 10 mg/kg on days 1 and 8 every 21 days or treatment of physician’s choice until disease progression or unacceptable toxicity. Follow-up was conducted at a median of 12.5 months. There were 272 patients in the experimental arm and 271 in the physician’s choice arm.

Results show that sacituzumab govitecan demonstrated a statistically significant and clinically meaningful improvements in overall survival (OS), as well as an improvement in progression-free survival (PFS).²

The median OS was 14.4 months with sacituzumab govitecan compared with 11.2 months with treatment of physician’s choice (HR, 0.79; 95% CI, 0.65-0.96; P = .02), representing a 3.2-month improvement in survival and a 21% relative reduction in the risk for death.² The median PFS of patients with HER2-low breast cancer treated with sacituzumab govitecan was 6.4 months vs 4.2 months in the standard of care arm (n =134; HR, 0.58; 95% CI, 0.42-0.79).³

Improvement in PFS was also shown in predefined subgroups of the study. For the IHC0 group, patients given sacituzumab govitecan (n = 101) had a median PFS of 5.0 months vs 3.4 when given physicians choice of chemotherapy (n = 116; HR, 0.72; 95% CI, 0.51-1.00). In the intention-to-treat population, the median PFS was 5.5 months (95% CI, 4.2-7.0) in the sacituzumab govitecan group vs 4.0 months (95% CI, 3.1-4.4) in the investigator’s choice chemotherapy group (HR, 0.66; 95% CI, 0.53-0.83; P < .0003).³

Efficacy results also showed that sacituzumab govitecan achieved an objective response rate of 21% vs 14% with physician’s choice (OR, 1.63; 95% CI, 1.03-2.56; P = .035). The clinical benefit rate was 34% for patients assigned sacituzumab govitecan and 22% for those assigned treatment of physician’s choice (OR, 1.8; 95% CI, 1.23-2.63; P = .003).²

The median duration of response was 8.1 months (95% CI, 6.7-9.1) with sacituzumab govitecan vs 5.6 months (95% CI, 3.8-7.9) with treatment of physician’s choice.

_REFERENCES:

_{1. U.S. FDA approves Trodelvy® in pre-treated HR+/HER2- metastatic breast cancer. News release. Gilead Sciences, Inc. February 3, 2023. Accessed February 3, 2023. https://bwnews.pr/3Rzki2W2}

_{2. 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). Annal Oncol. 2022;33(suppl 7): LBA76. Ddoi:10.1016/annonc/annonc1089}

_{3. New TROPiCS-02 data in HR+/HER2- metastatic breast cancer patients demonstrates progression-free survival benefit of trodelvy® regardless of their HER2 status. News release. Gilead Sciences, Inc. September 4, 2022. Accessed September 6, 2022. https://bit.ly/3qdhDyL}