Fast Track is based on the response rate and duration of the response and reinforces the premise that the Trop-2 antigen is an important target to be explored for the emergence of new therapies
Triple-negative breast cancer is now the most serious subtype among breast tumors. Although several traditional chemotherapeutics may have some degree of activity against metastatic disease, the control is short-lived and the patients’ life expectancy is less than two years.
Recently, the FDA (U.S. Food and Drug Administration) granted accelerated approval for sacituzumab govitecan-hziy for patients with metastatic triple-negative breast cancer who received at least two previous therapies.
Sacituzumab govitecan-hziy is a drug-antibody conjugate that combines a humanized monoclonal antibody targeting cell surface antigen 2 of human trophoblasts (Trop-2) with SN-38, which is conjugated to the antibody by a cleavable linker. Sacituzumab govitecan-hziy allows the administration of high concentrations of SN-38 in tumors.
Efficacy was demonstrated in IMMU-132-01 (NCT 01631552), a multi-center, single-arm, phase I / II trial that included 108 patients with metastatic triple-negative breast cancer (mTNBC) who received at least two previous treatments for metastatic disease. Patients received sacituzumab govitecan-hziy 10 mg / kg IV on days 1 and 8 every 21 days. Imaging tests were performed every 8 weeks and patients were treated until disease progression or therapy intolerance.
The main primary outcomes assessed by the investigator were overall response rate (ORR) using RECIST 1.1 and duration of response. The ORR was 33.3%, with 3 complete responses and 33 partial responses (95% CI: 24.6-43.1) and the median response duration was 7.7 months (95% CI: 4, 9-10.8). The clinical benefit rate was 45.4%. The median progression-free survival was 5.5 months (95% CI: 4.1-6.3) and the median overall survival was 13.0 months (95% CI: 11.2-13.7). Four deaths occurred during treatment; 3 patients (2.8%) discontinued treatment due to adverse events. Grade 3 or 4 adverse events (in ≥10% of patients) included anemia and neutropenia; 10 patients (9.3%) had febrile neutropenia.
Continuous approval may be subject to verification and description of the clinical benefit in confirmatory trials. This accelerated approval is based on the response rate and the duration of the response, and reinforces the premise that the Trop-2 antigen found in many solid cancers is an important target to be explored for the emergence of new therapies.
Bardia A, Mayer IA, Vahdat LT, Tolaney SM, Isakoff SJ, Diamond JR, O’Shaughnessy J, Moroose RL, Santin AD, Abramson VG, Shah NC. Sacituzumab govitecan-hziy in refractory metastatic triple-negative breast cancer. New England Journal of Medicine. 2019 Feb 21;380(8):741-51.