ALESIA: Long-term data support first-line alectinib in Asians with ALK-positive NSCLC

First-line treatment with alectinib appears to produce sustained clinical benefit in Asian patients with advanced, ALK-positive nonsmall cell lung cancer (NSCLC) through 5 years of follow-up, according to long-term data from the phase III ALESIA presented at the ESMO Asia Congress 2022.

Patients who received alectinib had a median progression-free survival (PFS) of 41.6 months, which is more than three times longer than the survival length associated with crizotinib (11.1 months) after a median follow-up of 51 months (hazard ratio [HR], 0.33, 95 percent confidence interval [CI], 0.23–0.49), reported Dr Thanyanan Baisamut of Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. [ESMO Asia 2022, abstract LBA11]

Alectinib also yielded a clinically meaningful improvement in overall survival (OS; HR, 0.60, 95 percent CI, 0.37–0.99), with more patients in the alectinib vs crizotinib group alive at 5 years after the start of treatment (66.4 vs 56.0 percent; patients remaining at risk, 69 vs 25), Baisamut said at ESMO Asia Congress 2022, adding that median OS had yet to be reached in both treatment arms.

More importantly, the PFS/OS benefit of alectinib occurred in patients regardless of central nervous system (CNS) involvement at baseline, she pointed out.

The corresponding HRs for PFS were 0.17 (95 percent CI, 0.09–0.33) and 0.45 (95 percent CI, 0.29–0.71) among patients with and without CNS involvement at baseline, respectively. Meanwhile, the HR for OS was 0.40 (95 percent CI, 0.19–0.85) among patients with CNS metastasis; there was no significant difference in OS in the two treatment arms among patients without CNS metastasis (HR, 0.81, 95 percent CI, 0.42–1.55).

Another promising effect of alectinib, according to Baisamut, was that the drug slowed down time to CNS progression (cause-specific HR, 0.16, 95 percent CI, 0.08–0.32), such that the estimated cumulative incidence of CNS progression events was markedly lower in the alectinib than in the crizotinib arm both at 3 years (11.6 percent vs 34.0 percent) and at 5 years (14.2 percent vs 37.4 percent).

“More crizotinib-treated patients received at least one anticancer therapy postprogression (77.1 percent vs 61.8 percent), [and] approximately 30 percent of patients in the crizotinib arm received alectinib after their disease progressed,” Baisamut added.

Overall, alectinib had a favourable safety profile despite longer treatment duration than crizotinib (42.3 vs 12.6 months), with fewer grade 3–5 adverse events (AEs; 48 percent vs 55 percent), serious AEs (28 percent vs 29 percent), and AEs leading to treatment discontinuation (11 percent vs 15 percent).

These 5-year data align with that reported in the primary analysis of the ALESIA study as well as the global ALEX study, with alectinib showing superior efficacy and lower toxicity in the primary treatment of ALK-positive NSCLC.  [Lancet Respir Med 2019;7:437-446; N Engl J Med 2017;377:829-838]

ALESIA included 187 treatment-naïve Asian patients with stage IIIB/IV ALK-positive NSCLC who had been randomized to receive alectinib 600 mg (n=125) or crizotinib 250 mg (n=62), administered twice daily until disease progression, toxicity, withdrawal, or death. The median duration of survival follow-up was 61 months in the alectinib arm and 51 months in the crizotinib arm.

“Th[e] clinical benefit, coupled with a tolerable and manageable safety profile, confirms alectinib as standard-of-care treatment for patients with advanced ALK-positive lung cancer,” Baisamut concluded.