Long-term efficacy and safety of entrectinib in ROS1 fusion-positive NSCLC
Chiu, C. H.
Cho, B. C.
Ahn, M. J.
Krebs, Matthew G
Liu, S. V.
Otterson, G. A.
Tan, D. S. W.
Doebele, R. C.
AffiliationDepartment of Medicine, Memorial Sloan Kettering Cancer Center, and Weill Cornell Medical College, New York
MetadataShow full item record
AbstractIntroduction: Entrectinib is an approved tyrosine kinase inhibitor (TKI) for ROS1 fusion-positive NSCLC. An updated integrated analysis of entrectinib from the ALKA-372-001, STARTRK-1, and STARTRK-2 trials is presented, with substantially longer follow-up, more patients, and the first description of the median overall survival (OS). An exploratory analysis of entrectinib in ROS1 fusion-positive NSCLC with the central nervous system (CNS)-only progression post-crizotinib is reported. Methods: Adults with ROS1 fusion-positive, locally advanced or metastatic NSCLC who received at least one dose of entrectinib and had 12 months or longer of follow-up were included in the analysis. Co-primary end points were confirmed objective response rate (ORR) and duration of response (DoR) by blinded independent central review. The data cutoff was on August 31, 2020. Results: The efficacy-assessable population comprised 168 ROS1 TKI-naïve patients. The median survival follow-up was 29.1 months (interquartile range, 21.8-35.9). The ORR was 68% (95% confidence interval [CI]: 60.2-74.8); the median DoR was 20.5 months. The median progression-free survival (PFS) was 15.7 months and the median OS was 47.8 months. In the 25 patients with measurable baseline CNS metastases, the intracranial ORR was 80% (95% CI: 59.3-93.2), median intracranial DoR was 12.9 months, and median intracranial PFS was 8.8 months. Among 18 patients with CNS-only progression on previous crizotinib treatment, two achieved a partial response (11%) and four had stable disease (22%). In seven patients with measurable CNS disease from this cohort, the intracranial ORR was 14% (1 partial response). Conclusions: Entrectinib is active and achieves prolonged survival in ROS1 TKI-naïve patients with ROS1 fusion-positive NSCLC. Modest activity is seen in patients with CNS-only progression post-crizotinib.
CitationDrilon A, Chiu CH, Fan Y, Cho BC, Lu S, Ahn MJ, et al. Long-Term Efficacy and Safety of Entrectinib in ROS1 Fusion–Positive NSCLC. Vol. 3, JTO Clinical and Research Reports. Elsevier BV; 2022. p. 100332.
JournalJTO Clinical and Research Reports
- Updated Integrated Analysis of the Efficacy and Safety of Entrectinib in Locally Advanced or Metastatic ROS1 Fusion-Positive Non-Small-Cell Lung Cancer.
- Authors: Dziadziuszko R, Krebs MG, De Braud F, Siena S, Drilon A, Doebele RC, Patel MR, Cho BC, Liu SV, Ahn MJ, Chiu CH, Farago AF, Lin CC, Karapetis CS, Li YC, Day BM, Chen D, Wilson TR, Barlesi F
- Issue date: 2021 Apr 10
- Entrectinib in ROS1 fusion-positive non-small-cell lung cancer: integrated analysis of three phase 1-2 trials.
- Authors: Drilon A, Siena S, Dziadziuszko R, Barlesi F, Krebs MG, Shaw AT, de Braud F, Rolfo C, Ahn MJ, Wolf J, Seto T, Cho BC, Patel MR, Chiu CH, John T, Goto K, Karapetis CS, Arkenau HT, Kim SW, Ohe Y, Li YC, Chae YK, Chung CH, Otterson GA, Murakami H, Lin CC, Tan DSW, Prenen H, Riehl T, Chow-Maneval E, Simmons B, Cui N, Johnson A, Eng S, Wilson TR, Doebele RC, trial investigators
- Issue date: 2020 Feb
- Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1-2 trials.
- Authors: Doebele RC, Drilon A, Paz-Ares L, Siena S, Shaw AT, Farago AF, Blakely CM, Seto T, Cho BC, Tosi D, Besse B, Chawla SP, Bazhenova L, Krauss JC, Chae YK, Barve M, Garrido-Laguna I, Liu SV, Conkling P, John T, Fakih M, Sigal D, Loong HH, Buchschacher GL Jr, Garrido P, Nieva J, Steuer C, Overbeck TR, Bowles DW, Fox E, Riehl T, Chow-Maneval E, Simmons B, Cui N, Johnson A, Eng S, Wilson TR, Demetri GD, trial investigators
- Issue date: 2020 Feb
- Updated Integrated Analysis of the Efficacy and Safety of Entrectinib in Patients With NTRK Fusion-Positive Solid Tumors.
- Authors: Demetri GD, De Braud F, Drilon A, Siena S, Patel MR, Cho BC, Liu SV, Ahn MJ, Chiu CH, Lin JJ, Goto K, Lee J, Bazhenova L, John T, Fakih M, Chawla SP, Dziadziuszko R, Seto T, Heinzmann S, Pitcher B, Chen D, Wilson TR, Rolfo C
- Issue date: 2022 Apr 1
- Entrectinib in children and young adults with solid or primary CNS tumors harboring NTRK, ROS1, or ALK aberrations (STARTRK-NG).
- Authors: Desai AV, Robinson GW, Gauvain K, Basu EM, Macy ME, Maese L, Whipple NS, Sabnis AJ, Foster JH, Shusterman S, Yoon J, Weiss BD, Abdelbaki MS, Armstrong AE, Cash T, Pratilas CA, Corradini N, Marshall LV, Farid-Kapadia M, Chohan S, Devlin C, Meneses-Lorente G, Cardenas A, Hutchinson KE, Bergthold G, Caron H, Chow Maneval E, Gajjar A, Fox E
- Issue date: 2022 Oct 3