Sacituzumab govitecan induced durable responses in patients with heavily pretreated metastatic triple-negative breast cancer, according to results of a phase 1/2 single-group trial published in The New England Journal of Medicine.
The antibody-drug conjugate also appeared safe among these patients, who achieved better outcomes than those associated with standard chemotherapy for triple-negative disease.
“Patients with metastatic triple-negative breast cancer have an aggressive tumor biology, but effective treatment options are limited,” Aditya Bardia, MD, director of precision medicine at the Center for Breast Cancer at Massachusetts General Hospital Cancer Center and assistant professor of medicine at Harvard Medical School, said in a press release. “Standard chemotherapy has been associated with low treatment response rates and considerable toxicity, highlighting the need for better therapies.”
Sacituzumab govitecan (IMMU-132, Immunomedics Inc.) combines an antibody to the Trop-2 antigen and releases SN-38, the metabolite of the chemotherapy drug irinotecan, directly into cancer cells and into the tumor microenvironment.
The trial included 108 patients (median age, 55 years; range, 31-80; 75.9% white) with triple-negative breast cancer who underwent a median of three (range, 2-10) prior anticancer treatments.
Participants received 10 mg/kg IV sacituzumab govitecan on days 1 and 8 of 21-day cycles.
Objective response rate, safety, duration of response, clinical benefit rate, PFS and OS served as trial endpoints.
Results showed a response rate of 33.3% (95% CI, 24.6-43.1), including three complete responses and 33 partial responses. Median duration of response was 7.7 months (95% CI, 4.9-10.8).
The clinical benefit rate, representing a complete or partial response or stable disease for at least 6 months, was 45.4%.
Seventy-seven patients had died and 94 patients experienced disease progression at data cutoff.
Researchers observed median PFS of 5.5 months (95% CI, 4.1-6.3) and median OS of 13 months (95% CI, 11.2-13.7). They estimated PFS probabilities of 41.9% at 6 months and 15.2% at 12 months, and OS probabilities of 78.5% at 6 months and 51.3% at 12 months.
Adverse events that occurred in at least 10% of patients included grade 3 and grade 4 neutropenia and anemia. Ten patients had febrile neutropenia. Nausea and diarrhea were the most common adverse events among all patients.
Four patients died during treatment and three stopped treatment because of adverse events.
A randomized phase 3 trial studying sacituzumab govitecan is currently recruiting patients in the United States and Europe.
“I think this drug has the potential to change practice, because the data looks so compelling, even with the relatively small number of patients in the trial,” Kevin Kalinsky, MD, assistant professor of medicine at Columbia University Vagelos College of Physicians and Surgeons, said in a press release. “There’s an unmet need for patients with metastatic triple-negative breast cancer, and we see significant tumor shrinkage with this new therapy.” – by John DeRosier
Disclosures: This study was funded by Immunomedics Inc. Bardia reports no relevant financial disclosures. Kalinsky reports an advisory role with Immunomedics Inc. and advisory and/or speaking roles with Amgen, Astra Zeneca, Biotheranostics, Eisai, Eli Lilly, Genentech, Ipsen, Novartis, Odonate Therapeutics and Pfizer. Please see the study for all other authors’ relevant financial disclosures.