FDA Approves Trodelvy for Pretreated Metastatic Triple-Negative Breast Cancer

The Food and Drug Administration (FDA) has approved Trodelvy (sacituzumab govitecan-hziy) for the treatment of adult patients with metastatic triple-negative breast cancer (TNBC) who have received at least two prior therapies for metastatic disease.

Trodelvy is an antibody-drug conjugate, which pairs a targeted drug with a potent chemotherapy agent. The chemotherapy used is irinotecan, and the targeted agent inhibits the activity of the protein TROP-2, which is expressed in more than 90% of patients with TNBC.

The approval is the first of an antibody-drug conjugate specifically for recurrent or treatment-resistant TNBC, and also the first of a drug in this class that targets TROP-2.

The approval was made under the FDA’s Accelerated Approval Program based on results from a single-arm, multicenter phase 2 study. Continued approval may depend upon verification of clinical benefit in the confirmatory phase 3 ASCENT study, which was recently stopped early due to very promising results to review.

In the phase 2 study, Trodelvy demonstrated an objective response rate — meaning the proportion of patients with tumor size reduction of a predefined amount and length of time — of 33.3% and a median duration of response of 7.7 months in 108 adult patients with TNBC who had previously received a median of three prior systemic therapies in the metastatic setting.

However, Trodelvy carries a black box warning, indicating a serious safety risk, for severe neutropenia (a drop in the number of neutrophils in the blood that can lead to infection) and severe diarrhea. The most common side effects occurring in 25% or more of participants included nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, hair loss, constipation, decreased appetite, rash and abdominal pain.

The most common serious or severe side effects, occurring in more than 5% of patients, were neutropenia, a decreased white blood cell count, anemia, a drop-in phosphate levels in the blood, diarrhea, fatigue, nausea and vomiting. Across all participating patients, 2% discontinued treatment due to side effects. There were no deaths related to treatment.

“The approval of Trodelvy, the first antibody-drug conjugate approved specifically for metastatic TNBC, an aggressive cancer with a poor prognosis and few effective therapies, will give clinicians a novel tool for treating patients with this disease,” the study’s lead investigator, Dr. Aditya Bardia, stated in a press release. “In our trial, Trodelvy demonstrated clinically meaningful responses in patients with difficult-to-treat metastatic TNBC and moves the needle toward better outcomes for patients with metastatic breast cancer,” added Bardia, director of precision medicine at the Center for Breast Cancer at Massachusetts General Hospital Cancer Center.

Check back later for what you need to know about this approval.