KEY TAKEAWAYS
- The study aimed to investigate the efficacy of adjuvant alectinib vs chemotherapy in resected ALK+ NSCLC.
- Researchers noted a significant DFS benefit with alectinib in resected ALK+ NSCLC, regardless of EML4-ALK variant and with implications for TP53 status.
ALINA (NCT03456076) is a global phase III randomized trial assessing the efficacy and safety of adjuvant alectinib versus chemotherapy in patients with resected stage IB (≥4 cm)–IIIA ALK+ non-small cell lung cancer (NSCLC) according to AJCC 7th edition criteria. The trial demonstrated a significant disease-free survival (DFS) advantage for alectinib over chemotherapy, with a hazard ratio of 0.24 (95% CI: 0.13–0.43, P<0.0001) in the intention-to-treat (ITT) population.
Ben J. Solomon and the team aimed to present the exploratory biomarker analyses derived from baseline tissue samples and matched samples from patients who experienced recurrence while on alectinib.
They performed an inclusive analysis of the biomarker-evaluable population (BEP), a subset of the ALINA ITT population. This group comprised patients who had sufficient baseline tumor tissue available for analysis and received valid results from the FoundationOne®CDx assay. Notably, patients from China were excluded from the BEP due to the lack of available baseline tissue samples.
The baseline characteristics and disease free survival (DFS), were noted between the ITT population (N=27) and the BEP (n=193). At the data cut-off in June 2023, 13 DFS events occurred in the alectinib group, while 41 events were recorded in the chemotherapy group within the BEP. A total of 81% of patients in the BEP had EML4-ALK fusions, with the most common variants being V1/V3; alectinib demonstrated a DFS benefit compared to chemotherapy, regardless of the EML4 variant.
The most frequently altered genes included CDKN2A, CDKN2B, TP53, and MTAP, with CDKN2A, CDKN2B, and MTAP alterations often co-occurring within single tumors. TP53 mutations were less common in patients with early-stage NSCLC from ALINA (24%) compared to those with metastatic NSCLC in the ALEX trial (NCT02075840) (41%).
In the alectinib arm, patients with wild-type (WT) TP53 exhibited a trend toward improved DFS compared to those with mutated TP53; this trend was not observed in the chemotherapy arm. No correlation between DFS and alterations in CDKN2A, CDKN2B, or MTAP was found for alectinib. Additionally, no ALK on-target resistance mechanisms were identified in the recurrence analysis.
The study concluded that alectinib provides a significant DFS benefit in patients with resected ALK+ NSCLC, independent of the EML4-ALK variant. Additionally, patients with WT TP53 at baseline exhibited a trend toward improved DFS compared to those with mutated TP53, highlighting the potential influence of TP53 status on treatment outcomes.
The trial was sponsored by the Hoffmann-La Roche.
Source: https://cslide.ctimeetingtech.com/esmo2024/attendee/confcal/show/session/162
Clinical Trial: https://clinicaltrials.gov/study/NCT03456076
Solomon B.J, Wu Y.L, Dziadziuszko R, et al. (2024). ” – ALINA: Exploratory biomarker analyses in patients (pts) with resected ALK+ non-small cell lung cancer (NSCLC) treated with adjuvant alectinib vs chemotherapy (chemo).” Presented at ESMO 2024 (Abstract 1206MO).
