Adjuvant alectinib boosts DFS in early stage, resected ALK+ NSCLC

Adjuvant targeted treatment with the anaplastic lymphoma kinase (ALK) inhibitor alectinib significantly improved disease-free survival (DFS) at 2 years compared with platinum-based chemotherapy in patients with early-stage, completely resected ALK-positive non-small cell lung cancer (ALK+ NSCLC) in the primary analysis of the phase III ALINA trial.

Alectinib reduced the risk of disease recurrence or death by 76 percent (hazard ratio [HR], 0.24, 95 percent confidence interval [CI], 0.13-0.45; p<0.0001) vs chemotherapy in the stage II–IIIA patient population (n=231). The same benefit was observed in the intention-to-treat (ITT) population (n=257, stage IB–IIIA), with HR of 0.24 (95 percent CI 0.13–0.43; p<0.0001). [ESMO 2023, abstract LBA2).

There was also a clinically meaningful improvement in the central nervous system (CNS) DFS (HR, 0.22, 95 percent CI, 0.08–0.58). “The CNS DFS benefit observed in the ITT population is incredibly important, given that patients with ALK+ disease have a high risk of brain metastases, occurring in about 50–60 percent of patients,” said presenting author Dr Ben Solomon from Peter MacCallum Cancer Centre, Melbourne, Australia.

Overall survival (OS) data were immature at the time of the analysis. The safety and tolerability of alectinib were consistent with prior studies in the metastatic setting.

New standard of care for resected ALK+ NSCLC?

Alectinib is a first-line treatment choice for metastatic NSCLC. “ALINA is the first phase III trial of an ALK inhibitor to show a DFS benefit in completely resected stage IB-IIIA disease,” said Solomon. “These potentially practice-changing data reinforce the potential of alectinib as a new standard of care in the ALK-positive early lung cancer setting where treatment options are currently extremely limited.”

Dr Levi Garraway, chief medical officer, and head of global product development at Genentech, commented that by reducing the risk of recurrence or death by an unprecedented 76 percent, alectinib can potentially alter the course of the disease.

Alectinib effective across all stages of the disease

The study enrolled adult patients with ECOG performance status of 0–1, who had completely resected stage IB-IIIA ALK+ NSCLC. They were randomly assigned 1:1 to alectinib 600 mg twice daily for up to 24 months or until disease recurrence, or up to four 21-day cycles of intravenous platinum-based chemotherapy.

Two-year DFS rates with alectinib and chemotherapy were 93.8 percent vs 63 percent, respectively, in the stage II–IIIA population and 93.6 percent vs 63.7 percent, respectively, in the ITT population. 

Over the course of therapy, grade 3–4  adverse events were reported in 30 percent of patients receiving alectinib and 31 percent of those receiving chemotherapy. There were no grade 5 AEs in either treatment arm. Rates of serious treatment-related AEs and AEs leading to treatment withdrawal were lower with alectinib than chemotherapy.

“Adjuvant alectinib was tolerated, in line with the known safety profile of the drug,” Solomon reported.

Despite the positive results, OS data are still immature, and long-term data are required for alectinib, commented discussant Professor Marina Garassino, director of the Thoracic Oncology Programme at the University of Chicago, Chicago, Illinois, US. “We should wait for the full results of the trial.”

Several trials of alectinib in stage I–III NSCLC are in progress given the unmet need of about 4–5 percent of NSCLC patients with ALK rearrangements, shared Solomon.