Blood first assay screening trial (BFAST) in patients (pts) with 1L NSCLC: ALK+ cohort updated biomarker analyses
Gadgeel SM, Yan M, Paul SM, Mathisen M, Mocci S, Assaf ZJ, Patel R, Sokol ES, Mok T, Peters S, Paz-Ares L, and Dziadziuszko R. Blood first assay screening trial (BFAST) in patients (pts) with 1L NSCLC: ALK+ cohort updated biomarker analyses. Annals of Oncology 2020; 31:S841.
Annals of Oncology
Background: BFAST (NCT03178552) is a global, multi-cohort study evaluating the relationship between blood-based next-generation sequencing (NGS) detection of actionable genetic alterations in circulating tumour DNA and activity of targeted therapies/immunotherapy in pts with 1L advanced NSCLC. In the ALK+ cohort, investigator-assessed objective response rate (ORR) was 87.4% and 12-month progression-free survival (PFS) rate was 78.4% with alectinib. We present updated ALK+ cohort biomarker analyses (median follow-up: 18.2 months). Methods: Pts aged ≥18 with stage III/IV ALK+ NSCLC (detected by blood-based NGS) received oral alectinib 600mg twice daily. Pre-treatment plasma samples were analysed for: co-occurring genetic alterations, ALK allele frequency, EML4 variants; their association with clinical outcomes was explored (adjusted [adj.] for sex, disease stage, performance and smoking status). Results: Of detected ALK fusions, 84% were EML4-ALK fusions. The most common EML4 variants (V) were V1 (34%) and V3 (33%), and the most common co-mutation was TP53 (44%). Pts with wild-type TP53 had improved 12-month PFS rate vs pts with mutated TP53 (89.4 vs 63.2%, respectively; adj. hazard ratio [HR] 0.31; 95% CI 0.14–0.68; P=.004). Worse 12-month PFS rate was seen for high (73.8%) vs low (81.5%) ALK allele frequency (50% allele cut-off [5.56 copies/mL; range: 0.43–686.28 copies/ml]: adj. HR 0.49; 95% CI 0.22–1.09; p=.08). No significant difference was seen in 12 month PFS rate between EML4 (78.9%) and non-EML4 (71.4%) fusions (adj. HR 0.91; 95% CI 0.33–2.49; p=.846) or EML4 V1 (87.5%) and V3 (74.1%) (adj. HR 0.53; 95% CI 0.18–1.55; p=.244). No significant difference in ORR was observed among the categories analysed. Conclusions: Molecular heterogeneity in ALK+ NSCLC may influence clinical efficacy of ALK inhibitors such as alectinib. Larger, more mature datasets are needed to identify and validate additional biomarkers predictive of limited benefit from ALK inhibitors. Clinical trial identification: NCT03178552.