Patients with advanced lung cancer might soon be offered a blood test that could help decide the best treatment for them, instead of relying on tumor biopsy analysis. New data from the BFAST trial presented by Gadgeel et al at the European Society for Medical Oncology (ESMO) Congress 2019 (Abstract LBA81) have shown that a blood assay can be used successfully to identify complex DNA mutations in the cells of patients with non–small cell lung cancer (NSCLC) suitable for some targeted treatments. The technique detects circulating tumor DNA.
Shirish Gadgeel, MBBS
“One of the biggest recent changes in treatment of NSCLC has been our ability to identify targetable genetic mutations that drive progression of the disease, but it is a major challenge to get a suitable tumor sample for analysis. We showed that liquid biopsy could be used to detect a complex type of driver mutation—ALK—in patients with NSCLC. These [patients] then responded at least as well to targeted therapy as in previous studies using conventional biopsy techniques,” explained presenting study author Shirish Gadgeel, MBBS, of Rogel Cancer Center, University of Michigan.
BFAST Details
In the phase II/III BFAST trial, 2,219 patients with stage IIIB/IV untreated NSCLC had blood-based next-generation sequencing of actionable genetic alterations. Results were obtained in 2,188 patients. Overall, 119 patients (5.4%) had ALK-positive disease and 87 of them were enrolled to receive alectinib.
Median follow-up was 12.6 months. Confirmed objective response rate reported by investigators was 87.4% (95% confidence interval [CI] = 78.5–93.5), and 12-month duration of response was 75.9% (95% CI = 63.6–88.2). Median progression-free survival was not reached, but 12-month progression-free survival reported by investigators was 78.4% (95% CI = 69.1–87.7). Safety data were consistent with the known safety profile of alectinib.
“Liquid biopsy identified a similar proportion of patients with ALK mutations to that typically seen with traditional biopsy, and the results with alectinib compared well with those seen in a pivotal study of this treatment,” said Dr. Gadgeel.
Commentary
Commenting on the results of the study, Alberto Bardelli, PhD, of the Department of Oncology, University of Turin, said “Rearrangement in the ALK gene described in the BFAST study is typically difficult to detect, so it is an important advance to have shown that it can be detected in the blood and used to guide ALK inhibitor treatment, which has then been demonstrated to be effective in patients with this mutation.
“It is encouraging to see that increasing numbers of patients with lung cancer can benefit from liquid biopsy to identify their disease mutation instead of tissue samples. At present, the technology is quite expensive, but as it becomes more widely used, the cost is likely to come down so that testing becomes more affordable and available in daily practice,” he added.
Disclosure: BFAST received funding from F. Hoffman-La Roche Ltd. For full disclosures of the study authors, visit esmo.org.
