Loading...
Efficacy and safety of entrectinib in locally advanced/metastatic ROS1 fusion-positive NSCLC: An updated integrated analysis
Krebs, Matthew G De Braud, F. Siena, S. Drilon, A. Doebele, R. C. Patel, M. R. Cho, B. C. Liu, S. V. Ahn, M. J. Chiu, C. H.
Krebs, Matthew G
De Braud, F.
Siena, S.
Drilon, A.
Doebele, R. C.
Patel, M. R.
Cho, B. C.
Liu, S. V.
Ahn, M. J.
Chiu, C. H.
Citations
Altmetric:
Abstract
Background: Entrectinib is a potent, selective, CNS active, ROS1 tyrosine kinase inhibitor
(TKI). In a preliminary analysis (data cut-off: 31 May 2018) of pts with ROS1
fusion-positive (ROS1-fp) NSCLC enrolled in phase 1/2 studies (ALKA-372-001,
STARTRK-1, STARTRK-2; EudraCT 2012-000148-88, NCT02097810, NCT02568267),
treatment with entrectinib produced clinically meaningful and durable systemic responses
with a manageable safety profile. We report on an updated integrated
analysis in a larger patient population with longer follow-up (data cut-off: 1 May
2019).
Methods: Enrolled pts were ROS1 TKI naïve with measurable disease; most received
entrectinib 600mg once daily. Tumours were assessed by blinded independent central
review using RECIST v1.1, after 4 wks and every 8 wks thereafter. Primary endpoints
were objective response rate (ORR) and duration of response (DoR). Progression-free
survival (PFS), overall survival (OS), efficacy in pts with/without baseline CNS metastases,
and safety were also assessed.
Results: The efficacy-evaluable population comprised 161 pts with ROS1-fp NSCLC;
baseline characteristics are shown (Table). Median follow-up: 15.8 months (range
0.1e43.2). ORR, 67.1% (95% CI 59.3e74.3); 14 pts (8.7%) achieved complete response,
94 (58.4%) partial response, 14 (8.7%) stable disease, 15 (9.3%) disease
progression. Median DoR, 15.7 months (95% CI 13.9e28.6); median PFS, 15.7 months
(95% CI 11.0e21.1); median OS, not estimable (NE) (95% CI 28.3eNE). In the subgroup
with prior immunotherapy (n¼24), ORR, 70.8% (95% CI 48.9e87.4). In pts with
investigator-assessed CNS metastases at baseline, ORR, 62.5% (95% CI 48.6e75.1).
The safety profile was similar to that previously reported.
Conclusions: This updated analysis, using a larger dataset with longer follow-up,
shows that entrectinib induces clinically meaningful responses in pts with ROS1-fp
NSCLC, including pts with CNS metastases at baseline.
Description
Date
2020
Publisher
Collections
Files
Loading...
From UNPAYWALL
Adobe PDF, 149.22 KB
Keywords
Type
Meetings and Proceedings
Citation
Krebs MG, De Braud F, Siena S, Drilon A, Doebele RC, Patel MR, et al. 1287P Efficacy and safety of entrectinib in locally advanced/metastatic ROS1 fusion-positive NSCLC: An updated integrated analysis. Annals of Oncology. 2020;31:S831-S3.