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Objective Since the first discovery of rearranged during transfection (RET) fusion in lung adenocarcinoma in 2011, two tyrosine kinase inhibitors, namely vandetanib and cabozantinib, are currently available. Despite favorable outcomes in systemic control, the intracranial therapeutic response remains insufficient. In this study, the clinical characteristics and outcomes of non-small cell lung cancer (NSCLC) patients with RET rearrangements were analyzed. Methods Patients with NSCLC harboring RET fusion who received treatment between January 2006 and January 2018 were analyzed. RET rearrangement was identified by FISH or NGS. Results A total of 59 patients were identified. About half of the patients were female (47.5%) and never smokers (50.9%). Most patients had adenocarcinoma (89.8%). A total of 17 patients (28.8%) had an intracranial lesion at the initial diagnosis of stage IV disease, and 11 additional patients (18.6%) developed intracranial metastases during follow-up. The median time to development of intracranial metastases was 19.0 months (95% CI: 9.6–28.5), resulting in a &amp;gt;60% cumulative incidence of brain metastasis at 24 months. The systemic efficacy of pemetrexed-based regimens was favorable with progression-free survival of 9.0 (95% CI: 6.9–11.2) and OS of 24.1 (95% CI: 15.2–33.0) months. The median progression-free survival for vandetanib and immunotherapy was 2.9 (95% CI: 2.0–3.8) and 2.1 (95% CI: 1.6–2.6) months, respectively. Conclusions Given the likelihood of RET-rearranged NSCLC progressing to intracranial metastases and the absence of apparent clinical benefit of currently available targeted or immunotherapeutic agents, development of novel treatment with higher selectivity and better penetration of the blood–brain barrier remains a priority.

Characteristics and outcomes of RET-rearranged Korean non-small cell lung cancer patients in real-world practice