1361P Alectinib for treatment-naïve advanced ALK+ NSCLC selected via blood-based NGS: Updated analyses of outcomes, circulating tumour (ct)DNA and biomarker subgroups from BFAST Cohort A
Recommended Citation
Gadgeel SM, Mok TS, Peters S, Nadal E, Han J, Alatorre Alexander JA, Leighl N, Sriuranpong V, Pérol M, Castro GD, de Marinis F, Tan DS, Paul S, Assaf ZJ, MacLennan M, Lohmann TO, Slade M, Mathisen MS, Bhagawati-Prasad V, Dziadziuszko R. 1361P Alectinib for treatment-naïve advanced ALK+ NSCLC selected via blood-based NGS: Updated analyses of outcomes, circulating tumour (ct)DNA and biomarker subgroups from BFAST Cohort A. Ann Oncol 2023; 34:S782-S783.
Document Type
Conference Proceeding
Publication Date
10-1-2023
Publication Title
Ann Oncol
Abstract
Background: BFAST (NCT03178552) is an ongoing global, open-label, multicohort study assessing the activity of therapies in patients (pts) with advanced/metastatic NSCLC harbouring actionable genetic alterations identified in ctDNA via NGS. In a previous analysis of the BFAST ALK+ NSCLC cohort, a high overall response rate (ORR) was reported in pts treated with alectinib. We present updated data with longer follow-up, and exploratory correlative ctDNA and biomarker analyses. Methods: Pts aged ≥18 years with treatment-naïve stage III/IV NSCLC had comprehensive genomic profiling via NGS on ctDNA at screening. Pts with ALK fusions (ALK+) received alectinib 600 mg twice daily. Primary endpoint: investigator (INV)-assessed ORR; key secondary endpoints: INV-assessed progression-free survival (PFS), duration of response (DOR), overall survival (OS), safety. Blood samples for exploratory analyses were collected every 2 cycles during treatment, and at disease progression if feasible. Results: The cohort included 87 ALK+ pts; median survival follow-up was 52.0 months (range 2.6–62.6). At data cutoff (24 Feb 2023), 34 (39.1%) pts remain on alectinib. Median PFS data for the overall population and per subgroup are presented in the table. In the overall population, ORR was 89.7% (95% CI 81.3–95.2); median DOR was 35.1 months (95% CI 24.8–49.7); 48-month OS rate was 58.3% (95% CI 47.8–68.7). Most pts (93%) had complete clearance of ctDNA (no ALK fusion reads) by Cycle 3 Day 1. Pts without ALK clearance had poor PFS (7.1 months; 95% CI 5.6–NE). No new safety signals were identified. Conclusions: BFAST is the first trial with mature clinical data using prospective blood-based NGS screening of ALK to select pts for treatment with alectinib. PFS data were consistent with the ALEX study. Concurrent TP53 mutation and high baseline ctDNA levels were associated with poorer prognosis; ctDNA clearance was associated with better outcomes. [Formula presented] Clinical trial identification: NCT03178552.
Medical Subject Headings
Hematology
PubMed ID
Not assigned.
Volume
34
First Page
S782
Last Page
S783
