Rearrangements in RET
RET gene rearrangements can cause tumorigenesis in approximately 1 to 2% of patients with NSCLC [73]. Multiple RET targeting TKIs that have shown clinical efficacy in patients with RET rearrangements are available in the market. Cabozantinib and Vendatinib have shown modest clinical efficacy with ORR of 28% and 18% and PFS of 5.5 months and 4.5 months respectively. [74, 75]
In another multicenter, multi-cohort clinical trial LIBRETTO-001, efficacy of selpercatinib was evaluated in patients with RET fusion positive NSCLC.In this study, 105 adult patients previously treated with platinum chemotherapy were treated with selpercatinibshowed ORR of 64% with 81% having responses lasting 6 months or longer. Selpercatinib was also given to 39 patients who never received systemic treatment before and was found to show ORR of 85% with 58% patients having responses lasting 6 months or greater. [76] Based on this trial, FDA granted accelerated approval to selpercatinib in metastatic RET fusion-positive NSCLC on May 8, 2020.