Screening using NGS in patients with metastatic NSCLC – initial results from the ALK-positive cohort
Next-generation sequencing (NGS) allows for obtaining a large amount of information about the tumor genome from a patient's blood sample. Currently, the method is recommended as an alternative in cases of insufficient tissue samples for standard biopsy examination. The first results of an ongoing prospective study provide insights into the role of NGS in mutation screening for patients with non-small cell lung cancer without a concurrent biopsy examination.
Testing the tumor genome
According to current guidelines, genetic testing for tumor alterations is recommended for advanced non-small cell lung cancer (NSCLC) to identify patients suitable for targeted therapy and immunotherapy.
The standard procedure for this purpose is a tumor biopsy. However, obtaining an adequate tissue sample for biopsy examination is often challenging – in Western countries, up to 38% of patients with metastatic NSCLC have insufficient samples for examination. Repeating the biopsy prolongs the diagnostic process, and a suitable sample for genetic testing may still not be obtained in some patients. The shortcomings of biopsy examination can now be mitigated through next-generation sequencing screening.
NGS panels allow for the sequencing of a wide array of genes in a single detailed test by analyzing circulating tumor DNA, with minimal input material from a patient's blood sample. The examination provides genetic mutation information relatively cheaply and quickly.
The ongoing open multi-cohort study Blood First Assay Screening Trial (BFAST) aims to detect mutations in patients with advanced NSCLC and subsequently evaluate the effectiveness of targeted therapy. Recently published analysis provides initial results from the ALK-positive cohort; other cohorts in the study include patients with mutations in the RET, ROS1, BRAF, EGFR genes in exon 20, and positive blood tumor mutational burden (TMB).
Analysis results
The cohort included patients over 18 years old with stage IIIB or IV NSCLC, where an ALK gene mutation was detected through screening, regardless of biopsy results, which were not a mandatory part of the study. These patients were assigned to 600 mg alektinib therapy twice daily. Screening was performed on a total of 2219 patients, with NGS results obtained for 98.6% of them. In 119 (5.4%) tested, an ALK gene mutation was found, and 87 were subsequently assigned to alektinib therapy.
The median follow-up period was 12.6 months (2.6–18.7). The objective response rate (ORR) assessed by investigators was 87.4% (95% confidence interval [CI] 78.5–93.5); independent review assessment was 92.0% (95% CI 84.1–96.7). The 12-month response rate confirmed by investigators was 75.9% (95% CI 63.6–88.2). In 35 patients with initial central nervous system (CNS) metastases, the ORR assessed by investigators was 91.4% (95% CI 76.9–98.2).
During the follow-up period, the median progression-free survival (PFS) was not reached. Investigator-assessed 12-month PFS was 78.4% (95% CI 69.1–87.7).
Therapy safety data were consistent with the known safety profile of alektinib.
Conclusion
The first cohort results from the ongoing BFAST study support the clinical application of next-generation sequencing in the diagnostic process for patients with ALK-positive NSCLC.
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Source: Dziadziuszko R., Mok T., Peters S. et al. Blood First Assay Screening Trial (BFAST) in treatment-naive advanced or metastatic NSCLC: initial results of the phase 2 ALK-positive cohort. J Thorac Oncol 2021 Jul 24, S1556–0864 (21) 02321–2, doi: 10.1016/j.jtho.2021.07.008 [Epub ahead of print].
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