Rearranged during transfection (RET) proto-oncogene gene fusions are rare in non-small-cell lung cancer (NSCLC). We compared the efficacy of pemetrexed-based chemotherapy with other chemotherapy regimens in patients with NSCLC with different RET fusion subtypes.

A retrospective, multicenter study of patients with pathologically confirmed stage IIIB/IV lung adenocarcinomas was conducted. RET rearrangements were detected using next generation sequencing. We analyzed the clinical characteristics of patients with RET-rearranged NSCLC and the efficacy of chemotherapy regimens. We also evaluated the efficacy between groups of patients with and without KIF5B-RET-rearranged lung cancer.

We evaluated 62 patients with NSCLC and RET rearrangements, including 41 with KIF5B-RET, 15 with CCDC6-RET, and 6 with other rare fusion subtypes. Of these 62 patients, 50 had stage IIIB/IV. We also evaluated 40 patients with first-line chemotherapy information available. The median progression-free survival was significantly different between those receiving pemetrexed-based chemotherapy and those receiving other chemotherapy regimens (9.2 vs. 5.2 months; P = .007). The median progression-free survival for patients with KIF5B-RET fusion and non-KIF5B-RET fusion was not significantly different statistically (7.8 vs. 11.2 months; P = .847). For second-line chemotherapy, a statistically significant difference was found between the chemotherapy regimens (4.9 vs. 2.8 months; P = .049). Survival follow-up data were available for 38 patients with advanced NSCLC. The median overall survival was 26.4 months. The overall survival of the patients with RET-rearranged NSCLC who had received pemetrexed-based chemotherapy versus no pemetrexed-based chemotherapy was 35.2 versus 22.6 months (P = .052). No difference in survival was observed between the patients with KIF5B-RET and non-KIF5B-RET rearrangements.

Pemetrexed-based treatment should be considered first when selecting the chemotherapy regimen for patients with NSCLC and RET rearrangements.