Alectinib Fails to Boost Overall Survival in ALK-Positive Non-Small Cell Lung Cancer

Patients with non-small cell lung cancer receiving alectinib did not have better results than patients receiving crizotinib.

Alectinib (Alecensa) failed to improve overall survival (OS) in comparison to crizotinib (Xalkori) in patients with treatment-naïve, advanced ALK-positive non–small cell lung cancer (NSCLC).

However, the data, which were presented during the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, may be confounded since 78.8% of patients who received crizotinib received alectinib initially.

In the primary analysis of the randomized, open-label phase 3 J-ALEX (JapicCTI-132316) study, alectinib demonstrated better progression-free survival (PFS) than crizotinib (HR, 0.34, 99.7% CI, 0.17-0.71; P = .0001). Median PFS was not reached with alectinib, compared to 10.2 months with crizotinib. Additional data from a data cut-off in June 2018 continued demonstrating better PFS for alectinib than crizotinib (HR, 0.37; 95% CI, 0.26-0.52). In the final analysis, investigators sought to examine OS data after a minimum of 5 years of follow-up.

“In this final analysis, from J-ALEX, prolongation of OS in the alectinib arm was not observed compared to crizotinib,” said Hiroshige Yoshioka, MD, of Kansaid Medical University Hospital, in a presentation of the findings. “However, median OS was not reached in either treatment arm. This OS result may have been confounded by crossover.”

Patients were randomized 1:1 to receive either alectinib (300 mg twice daily) or crizotinib (250 mg twice daily) until progressive disease (PD), unacceptable toxicity, withdrawal or death. Treatment crossover between arms was permitted after withdrawal.

Patients were eligible for the study if they were 20 years of age or older, had stage 3B, 4 or recurrent NSCLC, had ALK-positive disease, an ECOG score of 0-2, had ≥ 1 measurable lesion assessed by the investigator and had received 1 or less prior chemotherapy. Treated or asymptomatic brain metastases were allowed.

At a median follow-up of 68.6 months in the alectinib arm and 68 months in the crizotinib arm, deaths occurred in 40.8% and 39.4% of patients, respectively. Five-year survival rates for alectinib-treated patients were 60.85% compared to 64.11% in crizotinib-treated patients.

The global ALEX study, in which no major subsequent ALK TKIs as opposed to the J-ALEX study, including treatment crossover, demonstrated clinically meaningful OS improvement from alectinib compared to crizotinib in treatment-naïve, advanced ALK-positive NSCLC. OS data remain immature (HR, 0.67; 95% CI 0.46-0.98).


Yoshioka H, Hida T, Nokihara H, et al. Final OS analysis from the phase III j-alex study of alectinib (ALC) versus crizotinib (CRZ) in Japanese ALK-inhibitor naïve ALK-positive non-small cell lung cancer (ALK+ NSCLC). J Clin Oncol. 2021;39(suppl 15): 9022.