Efficacy/safety of entrectinib in patients (pts) with ROS1-positive (ROS1+) advanced/ metastatic NSCLC from the Blood First Assay Screening Trial (BFAST)
Recommended Citation
Peters S, Gadgeel SM, Mok TS, Nadal E, Kilickap S, Perol M, Cadranel J, Sugawara S, Chiu C, Moskovitz M, Yu C, Tanaka T, Nersesian R, Shagan SM, Maclennan M, Mathisen M, Bhagawati Prasad VN, Archer VR, Dziadziuszko R. Efficacy/safety of entrectinib in patients (pts) with ROS1-positive (ROS1+) advanced/ metastatic NSCLC from the Blood First Assay Screening Trial (BFAST). 2022; (17_suppl).
Document Type
Conference Proceeding
Publication Date
6-8-2022
Abstract
Background: Tissue-based biomarker testing remains challenging as tumor biopsies are often inadequate for comprehensive biomarker testing and repeat biopsies can be risky in pts with advanced/metastatic NSCLC. These challenges could be overcome by using blood-based testing to identify the most appropriate targeted therapy. BFAST (NCT03178552) is a global open-label, multicohort trial evaluating the efficacy and safety of selected therapies in pts with advanced/metastatic NSCLC harboring actionable genetic alterations, as identified by next-generation sequencing (NGS) in cell-free DNA (liquid biopsies). We present data from the ROS1+ cohort: this is the first evaluation of entrectinib efficacy in pts identified by prospective blood-based NGS. Methods: In this single-arm analysis, adults (ge;18 years) with treatment-naive measurable stage IIIB/IV NSCLC, identified as ROS1+ by the FoundationOne VR Liquid CDx CTA blood-based NGS test, received oral entrectinib 600 mg/day until disease progression (PD), unacceptable toxicity, consent withdrawal or death. Pts with asymptomatic brain metastases at screening were eligible. Tumor scans were performed at baseline and every 8 weeks thereafter for all disease involvement areas (brain imaging not mandated in pts without baseline CNS disease). Primary endpoint: investigator (INV)-assessed objective response rate (ORR; RECIST 1.1). Secondary endpoints: INV-assessed duration of response (DoR) and progression-free survival (PFS); independent review facility (IRF)-assessed ORR, DoR, PFS; overall survival (OS); time to CNS PD; safety. Results: 55 pts with ROS1+ NSCLC identified by blood-based NGS were enrolled and treated with entrectinib. Median age was 56 yrs; 58% of pts were female and 75% had no history of tobacco use. Non-squamous adenocarcinoma was the most common histology (n = 48/55; 87%); 4 pts (7.3%) had baseline CNS disease. Median follow-up: 18.3 months. At data cut-off (26 Nov 2021, n = 54 pts with measurable disease), confirmed ORR was 81.5% (n = 44/54; 95% CI 68.6-90.8) by INV (2 complete responses [CR], 42 partial responses [PR]) and IRF (3 CR, 41 PR). Median DoR was 13.0 months (95% CI 6.3-18.4) by INV and 16.7 months (95% CI 5.6-24.0) by IRF. Median PFS was 12.9 months (95% CI 8.7-18.5) by INV, and 14.8 months (95% CI 7.2-24.0) by IRF. OS data were immature with 20 events (36.4%) recorded. Median time to CNS PD was not reached (INV: 9 events; IRF: 6 events). Most treatment-related adverse events were non-serious with no treatment-related deaths. Conclusion: These data support the clinical value of blood-based NGS as another method to inform clinical decision-making in ROS1+ NSCLC. Pts with ROS1+ NSCLC (by blood-based NGS) treated with entrectinib showed deep and durable responses, consistent with results from entrectinib trials that used tissue-based testing. No new safety signals were observed.
Issue
17_suppl
