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.