Fast Five Quiz: Non–Small Cell Lung Cancer (NSCLC) and RET Mutation

Maurie Markman, MD


August 22, 2022

According to Drusbosky and colleagues, selpercatinib and pralsetinib are selective inhibitors that target RET alterations regardless of the tissue of origin. Selpercatinib was the first targeted therapy to be approved by the US Food and Drug Administration for tumors with RET mutations and is presently indicated for metastatic RET fusion–positive NSCLC. Accelerated approval in May 2020 for NSCLC was based on the open-label LIBRETTO-001 phase 1/2 clinical trial (N = 144). Objective response rate was 64% in treatment-experienced patients (N = 105) and 85% in treatment-naive patients (N = 39). The phase 3 confirmatory trial (LIBRETTO-431) is currently active.

When multitargeted TKIs were investigated for RET-altered NSCLC, response rates were modest and of limited duration. Toxicity could also be significant. RET fusions have also shown minimal response to immunotherapy. However, a pemetrexed-based chemotherapy regimen has been associated with modest activity in patients with RET-rearranged NSCLC.

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