According to exploratory biomarker analyses from the phase 3 ALINA trial, there was a benefit to disease-free survival with alectinib regardless of EML4-ALK variant among patients with NSCLC, and patients with wild-type TP53 showed a trend for improved DFS with alectinib compared to those with mutated TP53.

These data were first presented by Benjamin J Solomon, MBBS, PhD, Peter MacCallum Cancer Center, Melbourne, Australia, at the 2024 European Society for Medical Oncology (ESMO) Congress.

The global, open-label randomized phase 3 ALINA trial, enrolled 257 patients with resected, ALK-positive, stage IB, II, or IIIA, NSCLC. Patients were randomized on a 1-to-1 basis to receive either 600 mg alectinib twice daily (n = 130) for 24 months, or intravenous platinum-based chemotherapy for 4 cycles (n = 127). There has been a significant disease-free survival (DFS) benefit shown with alectinib vs chemotherapy. These exploratory biomarker analyses includes 193 patients from the biomarker-evaluable subpopulation, who had sufficient baseline tumor tissue available for analysis and a valid result from the FoundationOne®CDx assay.

At the time of data cutoff, there were 13 DFS events in the alectinib arm and 41 in the chemotherapy arm in the biomarker-evaluable subpopulation. Of that subpopulation, 81% had EML4-ALK fusions, the most common being V1/V3. Regardless of EML4 variant, there was a DFS benefit with alectinib vs chemotherapy. The most commonly altered genes were CDKN2A, CDKN2B, TP53 and MTAP. Alterations of CDKN2A, CDKN2B, and MTAP commonly co-occurred within single tumors. Patients with early-stage NSCLC from ALINA were less likely to exhibit TP53 mutations than patients with metastatic NSCLC from the ALEX trial. There was a trend for improved DFS among patients in the alectinib arm with wild-type TP53 when compared to patients with mutated TP53, and this trend was not seen in the chemotherapy arm. There were no correlations observed between DFS and CDKN2A, CDKN2B, or MTAP alterations for alectinib. 

Dr Solomon et al concluded, “In ALINA, DFS benefit with alectinib was seen regardless of EML4-ALK variant. Patients with [wild-type] TP53 at baseline showed a trend for improved DFS with alectinib vs mutated TP53.”

Source:

Solomon BJ, Wu YL, Dziadziuszko R, et al. ALINA: Exploratory biomarker analyses in patients (pts) with resected ALK+ non-small cell lung cancer (NSCLC) treated with adjuvant alectinib vs chemotherapy. Presented at the 2024 ESMO Congress. September 13-17, 2024; Barcelona, Spain. Abstract 1206MO