The FDA has granted an accelerated approval to the antibody-drug conjugate (ADC) sacituzumab govitecan-hziy (Trodelvy) for the treatment of adult patients with metastatic triple-negative breast cancer (TNBC) who have received at least 2 prior therapies for metastatic disease.
The approval was based on findings from a phase 1/2 study, in which, at a median follow-up of 9.7 months, the objective response rate (ORR) was 33.3% by local assessment (95% CI, 24.6%-43.1%) with a median duration of response (DOR) of 7.7 months (95% CI, 4.9-10.8). The clinical benefit rate (ORR plus stable disease) was 45.4%. By blinded independent central review, the ORR was 34.3% (95% CI, 25.4%-44.0%) and the median DOR was 9.1 months (95 CI, 4.6-11.3).
“The approval of Trodelvy, the first ADC 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,” Aditya Bardia, MD, the lead investigator of the phase 2 study, and director of Precision Medicine at the Center for Breast Cancer, Massachusetts General Hospital Cancer Center and Assistant Professor of Medicine at Harvard Medical School, 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 towards better outcomes for patients with metastatic breast cancer.”
Sacituzumab govitecan consists of the active metabolite of irinotecan, SN-38, linked with a humanized IgG antibody targeted against TROP-2, a cell-surface glycoprotein that is expressed in more than 90% of TNBC.
The phase I/II trial included 108 patients with TNBC at a median age of 55 years (range, 31-80). The majority of patients had visceral metastases (80%). Sacituzumab govitecan was administered at 10 mg/kg on days 1 and 8 of each 28-day cycle. Patients’ ECOG performance status was 0 (30%) and 1 (70%), and the median time from metastatic diagnosis to treatment in the study was 1.5 years. Overall, 57 patients had moderate (2+) to strong (3+) TROP-2 expression by immunohistochemistry and 5 had weak or absent staining for the marker. The data were not available for the remaining patients.
The median number of prior regimens was 3 (range, 2-10), which include checkpoint inhibitors for 16.7%. Additionally, 41% of patients were treated in the third-line setting and 59% were in the fourth-line or greater setting. The most common prior therapies were taxanes (98%), anthracyclines (86%), cyclophosphamide (85%), and platinum agents (75%).
The median progression-free survival (PFS) was 5.5 months (95% CI, 4.1-6.3). The estimated 6-month PFS rate 41.9%. By 12 months, the PFS rate with sacituzumab govitecan was estimated at 15.1%. The median overall survival (OS) was 13.0 months (95% CI, 11.2-13.7), with an estimated 6-month OS rate of 78.5% and a 12-month estimate of 51.3%.
Grade 3/4 adverse events (AEs) were experienced by 85% of patients receiving treatment with sacituzumab govitecan. Serious AEs were reported in 35% of patients. Overall, just 3 patients discontinued treatment due to AEs, of these 2 were deemed from study drug-related causes. Dose reductions to 7.5 mg/kg occurred in 25% of patients and the rest were able to continue sacituzumab govitecan at the 10 mg/kg dose.
The most common (≥10%) grade 3/4 AEs were neutropenia (41.7%), anemia (11%), decreased white-cell count (11%), hypophosphatemia (9%), diarrhea (8%), and fatigue and asthenia (8%). Ten patients (9.3%) developed febrile neutropenia during the course of the study. Additionally, 4 deaths occurred during treatment, and 3 patients discontinued due to AEs.
The confirmatory phase III ASCENT study exploring sacituzumab govitecan in patients with metastatic TNBC was recently stopped due to “compelling evidence of efficacy,” according to a statement from the company developing the antibody-drug conjugate, Immunomedics.
The company halted the trial based on a unanimous recommendation from the independent Data Safety Monitoring Committee. The ASCENT trial was launched to confirm the positive efficacy and safety results reported in a phase II study of the ADC in TNBC.
This article was originally published on OncLive as, "FDA Approves Sacituzumab Govitecan for TNBC."