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Intracranial Efficacy of Selpercatinib inFusion-Positive Non-Small Cell Lung Cancers on the LIBRETTO-001 Trial.
Clinical cancer research : an official journal of the American Association for Cancer Research2021IF: 3.6
Subbiah Vivek, Gainor Justin F, Oxnard Geoffrey R, Tan Daniel S W, Owen Dwight H, Cho Byoung Chul, Loong Herbert H, McCoach Caroline E, Weiss Jared, Kim Yu Jung, Bazhenova Lyudmila, Park Keunchil, Daga Haruko, Besse Benjamin, Gautschi Oliver, Rolfo Christian, Zhu Edward Y, Kherani Jennifer F, Huang Xin, Kang Suhyun
PMID: 34088726View on PubMed
Abstract
PURPOSE: We report the intracranial efficacy of selpercatinib, a highly potent and selective RET inhibitor, approved in the United States forfusion-positive non-small cell lung cancers (NSCLC). PATIENTS AND METHODS: In the global phase 1/2 LIBRETTO-001 trial (NCT03157128) in advanced-altered solid tumors, selpercatinib was dosed orally (160 mg twice every day) in 28-day cycles. Patients with baseline intracranial metastases had MRI/CT scans every 8 weeks for 1 year (12 weeks thereafter). In this pre-planned analysis of patients withfusion-positive NSCLC with baseline intracranial metastases, the primary endpoint was independently assessed intracranial objective response rate (ORR) per RECIST 1.1. Secondary endpoints included intracranial disease control rate, intracranial duration of response, and intracranial progression-free survival (PFS) independently reviewed. RESULTS: Eighty patients with NSCLC had brain metastases at baseline. Patients were heavily pretreated (median = 2 systemic therapies, range = 0-10); 56% of patients received ≥1 course of intracranial radiation (14% whole brain radiotherapy, 45% stereotactic radiosurgery). Among 22 patients with measurable intracranial disease at baseline, intracranial ORR was 82% [95% confidence interval (CI), 60-95], including 23% with complete responses. Among all intracranial responders (measurable and nonmeasurable,= 38), median duration of intracranial response was not reached (95% CI, 9.3-NE) at a median duration of follow-up of 9.5 months (IQR = 5.7, 12.0). At 12 months, 55% of intracranial responses were ongoing. In all 80 patients, median intracranial PFS was 13.7 months (95% CI, 10.9-NE) at a median duration of follow-up of 11.0 months (IQR = 7.4, 16.5). No new safety signals were revealed in patients with brain metastases compared with the full NSCLC trial population. CONCLUSIONS: Selpercatinib has robust and durable intracranial efficacy in patients withfusion-positive NSCLC.