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FDA Approves Pralsetinib for Metastatic RET Fusion–Positive NSCLC


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On September 4, the U.S. Food and Drug Administration (FDA) approved pralsetinib (Gavreto) for the treatment of adult patients with metastatic RET fusion–positive non–small cell lung cancer (NSCLC), as detected by an FDA-approved test. 

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

Pralesetinib is a once-daily oral RET-targeted therapy. It is designed to selectively and potently inhibit RET alterations that drive many cancer types, including approximately 1% to 2% of patients with NSCLC. Currently, RET is one of seven NSCLC biomarkers that can be targeted with an FDA-approved therapy.

Vivek Subbiah, MD

Vivek Subbiah, MD

“Targeted therapies have dramatically improved care for patients with NSCLC driven by oncogenes, including EGFR and ALK, and the approval of the selective RET inhibitor pralsetinib marks another milestone in a paradigm shift toward precision medicine,” said Vivek Subbiah, MD, Associate Professor of Investigational Cancer Therapeutics and 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. “Patients treated with pralsetinib had durable clinical responses, with a subset achieving complete responses characterized 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. This approval represents an important advance with the potential to change standards of care for patients with RET fusion–positive NSCLC, who have historically had limited treatment options.”

Response to Pralsetinib

Pralsetinib was granted accelerated approval by the FDA, and continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. In 87 patients previously treated with platinum-based chemotherapy, the overall response rate was 57% (95% confidence interval = 46%–68%) with a 5.7% complete response rate, and the median duration of response was not estimable (95% CI = 15.2 months–not estimable). In 27 treatment-naive patients who were ineligible for platinum-based chemotherapy per the study protocol, the overall response rate was 70% (95% CI = 50%–86%) with an 11% complete response rate, and the median duration of response was 9.0 months (95% CI = 6.3 months–not estimable). Pralsetinib has warnings and precautions of interstitial lung disease/pneumonitis, hypertension, hepatotoxicity, hemorrhagic events, risk of impaired wound healing, and risk of embryo-fetal toxicity.

Companion Diagnostic

Biomarker testing for RET is the only way to 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 with tumor tissue or liquid biopsies. In the ARROW trial, RET fusions were detected using next-generation sequencing, fluorescence in situ hybridization, or other methods.

The FDA granted premarket approval to Thermo Fisher Scientific's Oncomine Dx Target Test as a companion diagnostic to identify patients with RET fusion–positive metastatic NSCLC who are candidates for treatment with pralsetinib. The Oncomine Dx Target Test was initially approved in 2017 as the first targeted next-generation sequencing–based companion diagnostic for biomarkers associated with three FDA-approved NSCLC therapies. It is now also the first and only FDA-approved test of its kind for a targeted treatment for RET fusion–positive NSCLC. Thermo Fisher will update the Oncomine Dx Target Test to enable it to report RET fusions in the United States before the end of the year.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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