Updated efficacy and safety of entrectinib in NTRK fusion-positive non-small cell lung cancer

作者：Byoung Chul Cho, Chao‐Hua Chiu, Erminia Massarelli, Gary L. Buchschacher, Kōichi Goto, Tobias R. Overbeck, Herbert H. Loong, Cheng Ean Chee, Pilar Garrido, Xiaorong Dong, Yun Fan, Shun Lü, Sven Schwemmers, Walter Bordogna, Harald Zeuner, Stuart Osborne, Thomas John · 发表于：Lung Cancer · 年份：2023 · DOI：10.1016/j.lungcan.2023.107442 · 被引用次数：40 · 研究领域：Lung Cancer Treatments and Mutations、Melanoma and MAPK Pathways、Lung Cancer Research Studies

OBJECTIVES: NTRK fusions result in constitutively active oncogenic TRK proteins responsible for ∼ 0.2 % of non-small cell lung cancer (NSCLC) cases. Approximately 40 % of patients with advanced NSCLC develop CNS metastases; therefore, treatments with intracranial (IC) efficacy are needed. In an integrated analysis of three phase I/II studies (ALKA-372-001: EudraCT 2012-000148-88; STARTRK-1: NCT02097810; STARTRK-2: NCT02568267), entrectinib, a potent, CNS-active, TRK inhibitor, demonstrated efficacy in patients with NTRK fusion-positive (fp) NSCLC (objective response rate [ORR]: 64.5 %; 2 August 2021 data cut-off). We present updated data for this cohort. MATERIALS AND METHODS: Eligible patients were ≥ 18 years with locally advanced/metastatic, NTRK-fp NSCLC with ≥ 12 months of follow-up. Tumor responses were assessed by blinded independent central review (BICR) per RECIST v1.1 at Week 4 and every eight weeks thereafter. Co-primary endpoints: ORR; duration of response (DoR). Secondary endpoints included progression-free survival (PFS); overall survival (OS); IC efficacy; safety. Enrolment cut-off: 2 July 2021; data cut-off: 2 August 2022. RESULTS: The efficacy-evaluable population included 51 patients with NTRK-fp NSCLC. Median age was 60.0 years (range 22-88); 20 patients (39.2 %) had investigator-assessed baseline CNS metastases. Median survival follow-up was 26.3 months (95 % CI 21.0-34.1). ORR was 62.7 % (95 % CI 48.1-75.9), with six complete and 26 partial responses. Medi...