LAUSR

Rearranged during transfection (RET) fusions and epidermal growth factor receptor (EGFR) mutations are potent oncogenic drivers in patients with nonsmall cell lung cancer (NSCLC), but rarely co-exist. Concurrent RET/EGFR mutations have been reported in patients with NSCLC who develop resistance to EGFR tyrosine kinase inhibitors but are even less frequent in treatment-naïve patients. Consequently, there is no standard treatment for RET/EGFR-mutated NSCLC. We report a case of RET/EGFR mutant NSCLC successfully treated with the oral, potent, highly selective RET inhibitor selpercatinib (160 mg daily for 28-day cycles) in an ongoing phase II study in Chinese patients with NSCLC (LIBRETTO-321). The patient, a female nonsmoker, was diagnosed with de-novo left lung adenocarcinoma with neuroendocrine differentiation, and a RET fusion was detected by next-generation sequencing testing. The patient had two tumors in the pleura, a third in the subcarinal lymph node, and a nontarget tumor in the pleura. Pleural biopsy analysis confirmed a RET fusion KIF5B (K15;R12) and an EGFR exon 19 deletion. The patient achieved a partial response (PR) with selpercatinib (absence of target tumors in pleura and reduction in the size of lymph node tumor). The PR persisted for 14.7 months, with disease progression in the nontarget lesion in the pleura and a new lesion in the liver (the PR had persisted), resulting in the discontinuation of selpercatinib. The only notable adverse event was grade 3 elevated transaminase, that was effectively managed by dose reduction. These data may support the use of selpercatinib in patients with RET/EGFR co-mutated NSCLC.