On Feb. 3, 2023, the FDA approved sacituzumab govitecan-hziy (Trodelvy®, Gilead Sciences, Inc.) for the treatment of unresectable locally advanced or metastatic HR-positive, HER2-negative breast cancer in patients who have received endocrine-based therapy and at least 2 additional systemic therapies in the metastatic setting.¹ HER2-negative status is defined as IHC 0, IHC 1+ or IHC 2+/ISH–.

Sacituzumab is a first-in-class antibody-drug conjugate directed at Trop-2, a cell surface antigen that is highly overexpressed in multiple tumor types and is associated with poorer prognosis.² In the NCCN Guidelines, sacituzumab is a category 1 option for second-line treatment in selected patients.³

Sacituzumab carries black box warnings for severe or life-threatening neutropenia and severe diarrhea, which may require withholding treatment and initiating medications to prevent or treat these effects. Hypersensitivity and infusion reactions, including severe anaphylactic reactions, have occurred. This medicine should not be used during pregnancy.

In the TROPiCS-02 trial, which was the basis for the approval, the most frequent nonhematologic adverse events were diarrhea (62%), fatigue (60%), nausea (59%), and constipation (34%). Frequent myelosuppression included decreased leukocyte count (88%), neutrophil count (83%), hemoglobin (73%), and lymphocyte count (65%). Treatment was interrupted in 66% of patients because of adverse events.

Sacituzumab should be given only as an intravenous infusion, with a recommended schedule of dosing on days 1 and 8 of continuous 21-day treatment cycles. Premedication to prevent infusion reactions and chemotherapy-induced nausea and vomiting is recommended. Patients should be monitored during the infusion and for at least 30 minutes afterward.

The approval was based on results from the TROPiCS-02 trial, a randomized, active-controlled, open-label trial of 543 patients who received either sacituzumab or single-agent chemotherapy with eribulin, capecitabine, gemcitabine, or vinorelbine. Sacituzumab use lead to a significant 34% reduction in risk of disease progression or death (Table 1). At 1 year, the PFS rate was 21% in the sacituzumab govitecan arm vs 7% in the chemotherapy arm. In addition, overal survival (OS) in the sacituzumab arm was significantly longer, translating to a 21% reduction in the risk of death.

Table 1

PFS, progression-free survival; OS, overall survival; BICR, blinded independent central review.

Sacituzumab was approved in April 2021 for treatment of patients with triple-negative breast cancer who have received at least 2 prior systemic therapies.⁴ It also received accelerated approval for urothelial cancer in patients who have received a platinum-containing chemotherapy and PD-1 or PD-L1 inhibitor.⁵

References

1. Trodelvy (sacituzumab govitecan-hziy). Prescribing information. Gilead Sciences, Inc; 2023. Accessed February 13, 2023. https://www.gilead.com/-/media/files/pdfs/medicines/oncology/trodelvy/trodelvy_pi.pdf
2. Kalinsky K, Diamond JR, Vahdat LT, et al. Sacituzumab govitecan in previously treated hormone receptor-positive/HER2-negative metastatic breast cancer: final results from a phase I/II, single-arm, basket trial. Ann Oncol. 2020;31(12):1709-1718. doi:10.1016/j.annonc.2020.09.004
3. 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. August 3, 2022. https://www.gilead.com/news-and-press/company-statements/sacituzumab-govitecan-hziy-trodelvy-elevated-to-category-1-preferred-recommendation-in-second-line-metastatic-triple-negative-breast-cancer
4. US Food and Drug Administration. FDA grants regular approval to sacituzumab govitecan for triple-negative breast cancer. Updated April 8, 2021. Accessed February 14, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-regular-approval-sacituzumab-govitecan-triple-negative-breast-cancer
5. US Food and Drug Administration. FDA grants accelerated approval to sacituzumab govitecan for advanced urothelial cancer. Updated April 13, 2021. Accessed February 14, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sacituzumab-govitecan-advanced-urothelial-cancer