Abstract 1301P
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.
Editorial acknowledgement
Medical writing support was provided by Ben Castle, MSc, of Gardiner-Caldwell Communications and was funded by F. Hoffmann-La Roche Ltd.
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd.
Funding
F. Hoffmann-La Roche Ltd.
Disclosure
S.M. Gadgeel: Honoraria (self), Advisory/Consultancy: F. Hoffmann La-Roche Ltd/Genentech, AstraZeneca, Bristol-Myers Squibb, Novartis, Daiichi Sankyo, Boehringer Ingelheim and XCovery. M. Yan: Full/Part-time employment: F. Hoffmann-La Roche Ltd. S.M. Paul: Full/Part-time employment: Genentech, Inc; Shareholder/Stockholder/Stock options: F. Hoffmann-La Roche Ltd. M. Mathisen, S. Mocci, Z.J. Assaf, R. Patel: Full/Part-time employment: Genentech, Inc. E.S. Sokol: Full/Part-time employment: Foundation Medicine (a company fully owned by F. Hoffman-La Roche Ltd.; Shareholder/Stockholder/Stock options: F. Hoffman-La Roche Ltd. T. Mok: Leadership role: Sanonics Ltd, received honoraria/consulting fees from ACEA Biosciences, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Chimed, Cirina, F. Hoffmann La-Roche Ltd/Genentech, Fishawack Facilitate, Ignyta, Janssen, Lilly, Merck Serono, Merck; Research grant/Funding (self): AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, F. Hoffmann La-Roche Ltd, Merck Sharp & Dohme, Novartis, Pfizer, SFJ Pharmaceutical and XCovery. S. Peters: Advisory/Consultancy, Research grant/Funding (self): AbbVie, Amgen, AstraZeneca, Bayer, Biocartis, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F. Hoffmann-La Roche Ltd, Foundation Medicine, Illumina, Janssen, Merck Serono, Merck Sharp & Dohme, Merrimack; Honoraria (self): Takeda; Advisory/Consultancy, Research grant/Funding (self): Novartis. L. Paz-Ares: Shareholder/Stockholder/Stock options: Altum sequencing ; Advisory/Consultancy: Genentech/Roche, Loxo Oncology, Bayer, Eli Lilly, AstraZeneca, Pfizer, Bayer, Merck Sharp & Dohme, Novartis, Amgen, PharmaMar, Boehringer Ingelheim, Celgene, Servier, Sysmex, Incyte, Ipsen, Adacap, Sanofi, and Blueprint Medicines; Research grant/Funding (self), Officer/Board of Directors: BMS, AstraZeneca, and Merck Sharp & Dohme; Officer/Board of Directors: Genómica, Altum sequencing. R. Dziadziuszko: Honoraria (self), Advisory/Consultancy: F. Hoffmann La-Roche Ltd, FoundationMedicine, Pfizer, Boehringer Ingelheim, Novartis, AstraZeneca, Seattle Genetics, MSD and Takeda.