ALEX hits OS milestone in ALK+ NSCLC
Treatment with alectinib results in large survival gains versus crizotinib in advanced ALK-positive non–small-cell lung cancer (NSCLC), report the ALEX investigators at the European Society for Medical Oncology (ESMO) Congress 2025.
After 6 years of follow-up, the 152 patients treated with alectinib had a median overall survival (OS) of 81.1 months, compared with 54.2 months for the 151 treated with crizotinib, reported Tony Mok (Chinese University of Hong Kong).
This is probably one of the longest OS ever reported for stage 4 NSCLC.
Mok described the difference as clinically meaningful. The difference was not statistically significant; however, he noted that this may have been confounded by treatment crossover: 25.2% of patients in the crizotinib arm received alectinib as subsequent therapy.
The OS benefit compared with crizotinib was consistently observed across many subgroups, and the 7-year OS rate was 48.7% with alectinib versus 38.2% with crizotinib. The duration of response was 42.3 months with alectinib and 11.1 months with crizotinib, giving a significant hazard ratio of 0.41.
A clinically meaningful OS benefit was observed in patients both with or without central nervous system (CNS) metastases. In patients with CNS metastases at baseline and prior brain radiation, median OS was 92.0 months with alectinib versus 39.5 months with crizotinib.
There was no major difference between the two arms in toxicity. Increased blood bilirubin was the most common adverse event leading to dose reduction or treatment discontinuation with alectinib, and it was increased alanine transaminase for crizotinib.
Mok also considered subsequent treatment, stating that 8.6% in the alectinib arm had rechallenge versus 19.2% in crizotinib.
Discussant Christine Lovly (Vanderbilt University Medical Center, Nashville, Tennessee, USA) reflected that these results are “truly remarkable when you think about 2 decades earlier we were at about 8 months.”
Lovly noted that only 37.5% of patients in the alectinib arm received subsequent therapy and asked: “What is missing… why aren’t more patients receiving subsequent therapies?”
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