Dr Mok on Final OS Data From the ALEX Study Evaluating First-Line Alectinib in ALK+ NSCLC

“The message is not really the survival difference [between alectinib and crizotinib] but rather the number: the median OS [in the alectinib group] was 81 months. One other important message is that at 84 months, 48% of patients are still alive.”

Tony S.K. Mok, BMSc, MD, FRCP(C), FRCP(Edin), FHKCP, FHKAM(Medicine), FASCO, the Li Shu Fan Medical Foundation endowed Professor and Chairman of Department of Clinical Oncology at the Chinese University of Hong Kong, discussed final overall survival (OS) data for first-line alectinib (Alecensa) in patients with previously untreated, advanced ALK-positive non–small cell lung cancer (NSCLC) from the phase 3 ALEX trial (NCT02075840).

After 7 years of follow-up, the data from the ALEX study are now more mature, Mok began by stating. Accordingly, final OS data were presented during the 2025 ESMO Congress, and showed that first-line alectinib induced a clinically meaningful OS benefit and duration of response (DOR) when compared with crizotinib (Xalkori) in this patient population, regardless of baseline central nervous system metastasis.

At a median follow-up of 53.5 months with alectinib and 23.3 months with crizotinib, the 7-year OS rates were 48.6% vs 38.2%, respectively. Furthermore, the median OS in the alectinib arm (n = 152) reached 81.1 months (95% CI, 62.3-not evaluable) vs 54.2 months (95% CI, 34.6-75.6) in the crizotinib arm (n = 151). This outcome is particularly promising when contrasted with the historical median OS of less than 1 year for patients with NSCLC before the introduction of molecular targeting, Mok noted. Additionally, the median duration of response was 42.3 months (95% CI, 31.3-51.3) with alectinib (n = 126) and 11.1 months (95% CI, 7.9-13.0) with crizotinib (n = 115) in patients with previously untreated disease.

Despite this outcome, Mok acknowledged that statistically, there was no measurable difference in OS between the alectinib and crizotinib groups. This lack of statistical significance was attributed to 2 primary factors: the crossover that occurred between the treatment arms and the fact that the study was not powered to demonstrate OS benefits.

Mok emphasized that the most important information derived from these data was not the statistical difference in OS outcomes between arms, but the numerical median OS survival achieved with alectinib. Overall, these data continue to support the use of alectinib as a standard of care in the first line for patients with advanced ALK-positive NSCLC.