Adjuvant alectinib benefits Asians with resected ALK+ NSCLC

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

Compared with chemotherapy, alectinib reduced the risk of disease recurrence or death by 61 percent (hazard ratio [HR], 0.39, 95 percent confidence interval [CI], 0.18-0.85) in this Asian population with resected, stage IB–IIIA ALK+ NSCLC. [ESMO Asia 2023, abstract LBA1).

“Similarly, there was an improvement in central nervous system DFS with alectinib [HR, 0.24, 95 percent CI, 0.05–1.12],” reported study author Dr Jin Seok Ahn from Samsung Medical Center, Seoul, Republic of Korea. “At data cutoff, no overall survival events had been reported in the Asian subgroup.”

Adjuvant alectinib was tolerated, in line with the known safety profile of the drug. “Outcomes of patients recruited from Asia were comparable to that of the intention-to-treat (ITT) population in the global trial reported at ESMO 2023,” Ahn said.

First to show DFS benefit

ALK rearrangements are found in 4–5 percent of NSCLC patients, who are typically younger and non-smokers. “The results of ALINA reinforce the need for routine ALK testing across all stages of NSCLC,” he added.

Alectinib is a first-line treatment of choice for metastatic NSCLC. “ALINA is the first phase III trial of an ALK inhibitor to show DFS benefit in completely resected stage IB-IIIA disease,” Ahn pointed out. “These potentially practice-changing data reinforce the potential of alectinib as an important new treatment strategy for patients with stage 1B–IIIA ALK+ NSCLC, who currently have very limited treatment options.”

The global ALINA trial enrolled 257 adult patients from 26 countries with early-stage, resected ALK+ NSCLC and ECOG performance status 0–1. They were randomly assigned 1:1 to alectinib 600 mg twice daily (BID) for up to 24 months or until disease recurrence, or up to four 21-day cycles of intravenous platinum-based chemotherapy.

The exploratory subgroup comprised 140 patients enrolled from Asia (49 from Korea, 45 from Mainland China, 35 from Japan, 6 from Taiwan, and 5 from Thailand).

At the data cutoff on June 26, 2023, 25.4 percent of Asian patients in the alectinib group were still receiving treatment. The median follow-up was 27.6 months.

Global ALINA outcomes

Back at ESMO 2023 in Madrid, ALINA investigator Dr Ben Solomon from Peter MacCallum Cancer Centre, Melbourne, Australia, reported that two-year DFS with alectinib in the global population was 93.8 percent vs 63 percent with chemotherapy in stage II–IIIA population and 93.6 percent vs 63.7 percent, respectively, in the ITT population. [ESMO 2023, abstract LBA2]

“The CNS DFS benefit observed in the ITT population was incredibly important, given that patients with ALK+ disease have a high risk of brain metastases, occurring in about 50–60 percent of patients,” he said.

Throughout therapy, grade 3–4 adverse events (AEs) 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.

The safety and tolerability of alectinib were consistent with prior studies in the metastatic setting.

Targeted therapies are superior to conventional chemotherapy in ALK+ metastatic NSCLC. [Ann Oncol 2023;34:339-357] However, until the ALINA study, there is limited data on patients with resected ALK+ disease.

Discussant perspectives

“ALINA is a practice-changing trial,” commented study discussant Professor Sanjay Popat, consultant medical oncologist at the Royal Marsden Hospital in London, UK, at ESMO Asia 2023. “Adjuvant alectinib is the new standard of care for resected ALK+ NSCLC.”

“The data also support 600 mg BID as the standard alectinib dose in Asia, including in Japan,” he continued. “However, we don’t know what the regulatory and economic impact of the ALINA Asian outcomes will be in Japan, given that in the J-ALEX study of Japanese patients, alectinib was dosed at 300 BID.”

Moving on, additional follow-up is warranted for the ITT population to evaluate the event rate after alectinib discontinuation and the impact on survival, specifically because the patients did not receive chemotherapy.

“Meantime, we need to wait for the ctDNA and MRD* analyses to better understand who really needs adjuvant alectinib,” Popat said. “Finally, it will be important to define how we treat patients who relapse following adjuvant alectinib.”