Value of blood-based screening for ALK fusions shown in patients with NSCLC
medwireNews: Blood-based next-generation sequencing (NGS) can be used to identify patients with non-small-cell lung cancer (NSCLC) and ALK fusions who will benefit from treatment with alectinib, show results of the phase II/III blood-first assay screening trial (BFAST).
Shirish Gadgeel (University of Michigan, Ann Arbor, USA) presented the findings at the ESMO Congress 2019 in Barcelona, Spain.
He told delegates that, during the study, 2219 adults with stage IIIB/IV NSCLC were screened for actionable genetic alterations using only blood-based NGS.
Of these, 119 (5.4%) had ALK fusions and 87 (median age 55 years, 40% men) underwent treatment with alectinib 600 mg twice daily until unmanageable toxicity, treatment withdrawal, or death.
Within the ALK-positive alectinib-treated cohort, the most common fusion partner was EML4, which was detected in 83.9% of cases. In addition, 43.7% of patients had a TP53 mutation, and the median blood-based tumor mutational burden was 2 mutations/Mb but ranged from 0 to 21 mutations/Mb.
Gadgeel reported that during a median follow-up period of 12.6 months, the investigator-assessed overall response rate (ORR) was 87.4%, all of which were partial responses. Upon independent review the ORR increased to 92.0% and included a complete response rate of 12.6%.
By comparison, the confirmed ORR in the ALEX trial of alectinib, which used a tissue-based assay to determine ALK mutation status, was 71.7%.
Gadgeel also pointed out that the investigator-assessed ORR was similar between patients who did (n=35) and did not (n=52) have central nervous system metastases at baseline, at 91.4% and 84.6%, respectively.
Median progression-free survival (PFS) duration has not yet been reached, but at 12 months, 78.4% of patients were alive and without disease progression. In the ALEX trial, the 12-month PFS rate was 68.4%, Gadgeel remarked.
Furthermore, the majority (90.4%) of patients had a response duration of at least 6 months, while approximately three-quarters had a response that lasted for at least 12 months.
Gadgeel noted that the safety profile was consistent with that previously reported for alectinib, with the most common adverse events being constipation (38%) and peripheral edema (37%). Grade 3 or 4 adverse events were reported by 35% of patients and 6% experienced a serious treatment-related adverse event.
Treatment discontinuation as a result of an adverse event occurred in six (7%) patients, seven (8%) required a dose reduction, and 27 (31%) had a dose interruption during the course of the study.
Gadgeel concluded: “BFAST is the first prospective trial to use blood-based NGS testing as the sole method of identifying actionable genetic alterations and assigning NSCLC patients to targeted or immunotherapy.”
He added: “These results demonstrate the clinical utility of blood-based NGS as a method to inform clinical decision-making in ALK-positive NSCLC.”
By Laura Cowen
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