Pralsetinib gets US FDA approval to treat RET fusion-positive non-small cell lung cancer

September 8, 2020 0 By FM

The U.S. FDA has recently approved pralsetinib (Gavreto) for the treatment of adult patients with metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC).

The approval is based on data from the phase 1/2 ARROW clinical trial, which showed efficacy for pralsetinib in patients with RET fusion-positive NSCLC with or without prior therapy, and regardless of RET fusion partner or central nervous system involvement.

Pralsetinib is a once-daily oral RET-targeted therapy that selectively and potently inhibits RET alterations that drive many cancer types, including approximately 1 to 2 percent of patients with NSCLC.

Biomarker testing for RET help identify patients with metastatic NSCLC who are candidates for treatment with pralsetinib. RET fusions can be identified with available biomarker tests, including next-generation sequencing (NGS) with tumour tissue or liquid biopsies. In the ARROW trial, RET fusions were detected using NGS, FISH or other methods.

“Patients treated with pralsetinib had durable clinical responses, with a subset achieving complete responses characterised by the resolution of all target lesions, an uncommon outcome in metastatic lung cancer. We observed this activity with or without prior therapy and regardless of RET fusion partner or the presence of brain metastases.” said Vivek Subbiah, M.D., associate professor of Investigational Cancer Therapeutics and center medical director of the Clinical Center for Targeted Therapy at The University of Texas MD Anderson Cancer Center, and an investigator on the ARROW trial.

In 87 patients previously treated with platinum-based chemotherapy, the overall response rate (ORR) was 57 percent (95% CI: 46%, 68%) with a 5.7 percent complete response (CR) rate, and the median duration of response (DOR) was not estimable. In 27 treatment-naïve patients who were ineligible for platinum-based chemotherapy per the study protocol, the ORR was 70 percent (95% CI: 50%, 86%) with an 11 percent CR rate, and the median DOR was 9.0 months.

Pralsetinib has warnings and precautions of interstitial lung disease/pneumonitis, hypertension, hepatotoxicity, haemorrhagic events, risk of impaired wound healing and risk of embryo-foetal toxicity.