Updated efficacy and safety of entrectinib in NTRK fusion-positive non-small cell lung cancer
- Author(s)
- Cho, BC; Chiu, CH; Massarelli, E; Buchschacher, GL; Goto, K; Overbeck, TR; Loong, HHF; Chee, CE; Garrido, P; Dong, X; Fan, Y; Lu, S; Schwemmers, S; Bordogna, W; Zeuner, H; Osborne, S; John, T;
- Journal Title
- Lung Cancer
- Publication Type
- Research article
- Abstract
- OBJECTIVES: NTRK fusions result in constitutively active oncogenic TRK proteins responsible for approximately 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. Median DoR and PFS were 27.3 months (95 % CI 19.9-30.9) and 28.0 months (95 % CI 15.7-30.4), respectively. Median OS was 41.5 months. In patients with BICR-assessed baseline CNS metastases, IC-ORR was 64.3 % (n = 9/14; 95 % CI 35.1-87.2), including seven complete responders, and IC-DoR was 55.7 months. In the safety-evaluable population (n = 55), most treatment-related adverse events were grade 1/2; no treatment-related deaths were reported. CONCLUSION: Entrectinib has continued to demonstrate deep and durable systemic and IC responses in patients with NTRK-fp NSCLC.
- Keywords
- Humans; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; *Carcinoma, Non-Small-Cell Lung/drug therapy/genetics/pathology; *Lung Neoplasms/drug therapy/genetics/chemically induced; *Antineoplastic Agents/therapeutic use; Indazoles; *Central Nervous System Neoplasms/drug therapy/genetics; Protein Kinase Inhibitors/adverse effects; *Benzamides; Cns; Entrectinib; Intracranial; Nsclc; NTRK fusions
- Department(s)
- Medical Oncology
- PubMed ID
- 38171156
- Publisher's Version
- https://doi.org/10.1016/j.lungcan.2023.107442
- Open Access at Publisher's Site
https://doi.org/10.1016/j.lungcan.2023.107442- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2024-08-20 03:42:01
Last Modified: 2024-08-20 06:57:07