Novel antibody-drug conjugate shows promise for advanced triple-negative breast cancer

Sacituzumab govitecan — a novel antibody-drug conjugate — produced durable responses and appeared well-tolerated among pretreated patients with metastatic triple-negative breast cancer, according to results of a single-arm, multicenter, phase 2 trial.

“This approach may represent a new therapy paradigm for this difficult-to-treat disease, which is typically associated with an aggressive tumor biology and poor survival,” Aditya Bardia, MD, MPH, of Massachusetts General Hospital Cancer Center, said in a press release accompanying the study.

“Triple-negative breast cancer disproportionally affects younger patients, particularly premenopausal African American women, and frequently displays homologous recombination deficiency and high genomic instability that may predict sensitivity to DNA–damaging agents, such as platinum and DNA repair inhibitors, including poly(ADP-ribose) polymerase-1 inhibitors,” Bardia and colleagues wrote. “The management of triple-negative breast cancer could be improved by the development of specific targeted agents because most available drugs achieve PFS of < 3.5 months.”

Patients with relapsed or refractory triple-negative breast cancer (n = 69) received a 10mg/kg starting dose on days 1 and 8 in a 21-day repeating cycle.

Patients received a median of five therapies (range, 1-12) prior to the trial.

Thirty percent of patients achieved an objective response (complete response, n = 2; partial response, n = 19), with a median duration of response of 8.9 months (95% CI, 6.1-11.3).

The clinical benefit rate — complete response, partial response and stable disease ≥ 6 months — was 46%. The median onset of response was 1.9 months. Median PFS was 6 months (95% CI, 5-7.3), and median OS was 16.6 months (95% CI, 11.1-20.6).

Researchers reported several adverse events of grade 3 or higher: neutropenia (39%), leukopenia (16%), anemia (14%), diarrhea (13%), and febrile neutropenia (7%).

Most tumor specimens showed an immunohistochemistry positive for Trop-2 (88%). Bardia and colleagues reported no neutralizing antibodies in response to the antibody-drug conjugate.

“Single-agent treatment with sacituzumab govitecan was well tolerated and highly active in heavily pretreated patients with metastatic triple-negative breast cancer,” the researchers wrote. “On the basis of discussions with regulatory authorities and the Breakthrough Therapy designation for metastatic triple-negative breast cancer from the FDA, the study of a more restricted patient population with at least two prior therapies for metastatic disease is currently underway.” – by Andy Polhamus

Disclosure: Bardia reports consulting or advisory roles with Genentech and Novartis. Please see the study for a full list of all other researchers’ relevant financial disclosures.