Updated integrated analysis of the efficacy and safety of entrectinib in locally advanced or metastatic ROS1 fusion-positive non-small-cell lung cancer
Krebs, Matthew G
De Braud, F.
Doebele, R. C.
Patel, M. R.
Cho, B. C.
Liu, S. V.
Ahn, M. J.
Chiu, C. H.
Farago, A. F.
Lin, C. C.
Karapetis, C. S.
Li, Y. C.
Day, B. M.
Wilson, T. R.
AffiliationMedical University of Gdańsk, Gdańsk, Poland
MetadataShow full item record
AbstractPurpose: Genetic rearrangements of the tyrosine receptor kinase ROS proto-oncogene 1 (ROS1) are oncogenic drivers in non-small-cell lung cancer (NSCLC). We report the results of an updated integrated analysis of three phase I or II clinical trials (ALKA-372-001, STARTRK-1, and STARTRK-2) of the ROS1 tyrosine kinase inhibitor, entrectinib, in ROS1 fusion-positive NSCLC. Methods: The efficacy-evaluable population included adults with locally advanced or metastatic ROS1 fusion-positive NSCLC with or without CNS metastases who received entrectinib ≥ 600 mg orally once per day. Co-primary end points were objective response rate (ORR) assessed by blinded independent central review and duration of response (DoR). Secondary end points included progression-free survival (PFS), overall survival (OS), intracranial ORR, intracranial DoR, intracranial PFS, and safety. Results: In total, 161 patients with a follow-up of ≥ 6 months were evaluable. The median treatment duration was 10.7 months (IQR, 6.4-17.7). The ORR was 67.1% (n = 108, 95% CI, 59.3 to 74.3), and responses were durable (12-month DoR rate, 63%, median DoR 15.7 months). The 12-month PFS rate was 55% (median PFS 15.7 months), and the 12-month OS rate was 81% (median OS not estimable). In 24 patients with measurable baseline CNS metastases by blinded independent central review, the intracranial ORR was 79.2% (n = 19; 95% CI, 57.9 to 92.9), the median intracranial PFS was 12.0 months (95% CI, 6.2 to 19.3), and the median intracranial DoR was 12.9 months (12-month rate, 55%). The safety profile in this updated analysis was similar to that reported in the primary analysis, and no new safety signals were found. Conclusion: Entrectinib continued to demonstrate a high level of clinical benefit for patients with ROS1 fusion-positive NSCLC, including patients with CNS metastases.
CitationDziadziuszko R, Krebs MG, De Braud F, Siena S, Drilon A, Doebele RC, et al. Updated Integrated Analysis of the Efficacy and Safety of Entrectinib in Locally Advanced or Metastatic ROS1 Fusion-Positive Non-Small-Cell Lung Cancer. J Clin Oncol. 2021:JCO2003025.
JournalJournal of Clinical Oncology
- 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
- The European Medicines Agency review of entrectinib for the treatment of adult or paediatric patients with solid tumours who have a neurotrophic tyrosine receptor kinase gene fusions and adult patients with non-small-cell lung cancer harbouring ROS1 rearrangements.
- Authors: Delgado J, Pean E, Melchiorri D, Migali C, Josephson F, Enzmann H, Pignatti F
- Issue date: 2021 Apr
- Entrectinib: A Review in NTRK+ Solid Tumours and ROS1+ NSCLC.
- Authors: Frampton JE
- Issue date: 2021 Apr
- Patient-reported outcomes from STARTRK-2: a global phase II basket study of entrectinib for ROS1 fusion-positive non-small-cell lung cancer and NTRK fusion-positive solid tumours.
- Authors: Paz-Ares L, Barlesi F, Siena S, Ahn MJ, Drilon A, Conley A, Rolfo C, Wolf J, Seto T, Doebele R, Kapre A, Chen D, McCallum S, Osborne S, Demetri G
- Issue date: 2021 Jun