Gilead’s Trodelvy Gets FDA Nod for Breast Cancer Treatment

Gilead recently announced that FDA approved Trodelvy for adults with unresectable, locally advanced, or metastatic triple-negative breast cancer (TNBC).

FDA based its approval on results from a Phase 3 study, ASCENT, in which Trodelvy demonstrated a statistically significant 57 percent reduction in the risk of disease worsening or death.

Additionally, the drug extended median overall survival to 11.8 months versus 6.9 months, representing a 49 percent reduction.

The most frequent adverse reactions for Trodelvy compared to single-agent chemotherapy were neutropenia, diarrhea, leukopenia, and anemia. Just five percent of patients who experienced adverse reactions discontinued treatment.

Prior to the FDA approval, patients with previously treated metastatic TNBC had few treatment options.

“Women with triple-negative breast cancer have historically had very few effective treatment options and faced a poor prognosis,” Aditya Bardia, MD, MPH, director of breast cancer research program at Mass General Cancer Center and assistant professor of medicine at Harvard Medical School, said in the announcement.

“Today’s FDA approval reflects the statistically significant survival benefit seen in the landmark ASCENT study and positions sacituzumab govitecan-hziy as a potential standard of care for pre-treated TNBC,” Bardia, who is also the global principal investigator of the ASCENT study, continued.

Gilead explained that Trodelvy is a Trop-2 receptor, a protein frequently expressed in various types of epithelial tumors, including TNBC.

Last April, FDA granted accelerated approval to Trodelvy based on objective response rate and duration of response results in a Phase 1/2 study.

In the study, researchers uncovered that median primary efficacy endpoint for patients receiving Trodelvy was 4.8 months versus to 1.7 months in those receiving chemotherapy. The most common adverse reactions included nausea, neutropenia, diarrhea, fatigue, and anemia.  

The recent approval expands the previous Trodelvy indication to include treatment in adult patients with unresectable locally advanced or metastatic TNBC who have received two or more prior systemic therapies, Gilead explained.

“Today’s approval is the culmination of a multi-year development program and validates the clinical benefit of this important treatment in metastatic TNBC,” said Merdad Parsey, MD, PhD, chief medical officer at Gilead.

“Building upon this milestone, we are committed to advancing Trodelvy with worldwide regulatory authorities so that, pending their decision, Trodelvy may become available to many more people around the world who are facing this difficult-to-treat cancer,” Parsey continued.

Regulatory submissions for Trodelvy in metastatic TNBC have been filed in the UK, Canada, Switzerland, and Australia as part of the FDA Oncology Center of Excellence (OCE). The European Medicines Agency has also validated a marketing authorization application for Trodelvy in the EU.  

Ricki Fairley, founder and CEO of Touch, the Black Breast Cancer Alliance, emphasized that it is a significant advance to have an FDA-approved treatment option with proven survival benefits for patients with TNBC.

This approval is progress to bringing more options to treat this disease.

TNC accounts for 15 to 20 percent of breast cancer cases and 25 percent of all breast cancer deaths. Top pharmaceutical companies, including Roche and Merck, have put forth effort to develop potential treatment options.

But mid-August, Roche announced that a Phase 3 study evaluating its lung cancer drug, Tecentriq, combined with chemotherapy, did not meet its primary endpoint for treatment of metastatic triple-negative breast cancer (TNBC) with expressed PD-L1 compared to placebo.

The data for the secondary endpoint of overall survival also showed a negative trend.

And at the beginning of April, FDA issued a Complete Response Letter (CRL) regarding Merck’s supplemental Biologics License Application (sBLA) seeking approval for its monoclonal antibody, Keytruda.

Keytruda is Merck’s anti-PD-1 therapy for the treatment of patients with high-risk early-stage triple-negative breast cancer in combination with chemotherapy as pre-operative treatment.

In the CRL, FDA’s Oncologic Drugs Advisory Committee voted 10 to 0 that a regulatory decision about Keytruda should be deferred until further data are available from its Phase 3 clinical trial, KEYNOTE-522.

Merck stated that it is reviewing the recent CRL and will discuss next steps with FDA.