Alectinib Outperforms Crizotinib in ALK+ Lung Cancer

Alectinib is better tolerated and is associated with longer progression-free survival (PFS) than crizotinib as a first-line treatment for patients with ALK mutation–positive non–small-cell lung cancer (ALK+ NSCLC), according to follow-up safety and efficacy findings from the phase III ALEX study (abstract 9043) presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 1–5 in Chicago.

“Alectinib demonstrated superior efficacy vs crizotinib regardless of baseline central nervous system [CNS] metastases,” reported D. Ross Camidge, MD, PhD, of the University of Colorado in Aurora, and coauthors. “The quality of response with alectinib was highlighted by the longer duration and greater depth of response compared with crizotinib, in patients with and without CNS metastases at baseline.”

Alectinib was also consistently more tolerable despite longer treatment, “consolidating alectinib as the standard of care for the first-line treatment of patients with ALK+ NSCLC,” the study authors noted.

Alectinib is a highly selective ALK inhibitor that is active in brain tissue; it was approved in November 2017 by the US Food and Drug Administration for treating patients with metastatic ALK+ NSCLC.

Among the intent-to-treat study population at the cutoff for updated data, 47% of patients who received alectinib and 76.8% of those receiving crizotinib had experienced disease progression or had died. Investigator-assessed PFS was 34.8 months in the alectinib study group (n = 152) compared with 10.9 months in the crizotinib group (n = 151; hazard ratio [HR], 0.43; 95% CI, 0.32–0.58). Among patients with brain metastases at baseline, PFS was 27.7 months vs 7.4 months (HR, 0.35; 95% CI, 0.22–0.56).

Response rates were 82.9% and 75.5% for the alectinib and crizotinib study groups. Seven of 152 patients on alectinib had complete responses, compared with 3 of 151 patients on crizotinib; partial responses were reported for 119 of 152 patients on alectinib, compared with 111 of 152 on crizotinib.

“The proportion of patients with grade 3–5 adverse events was lower with alectinib (45%) than with crizotinib (51%), [and] the proportions of patients with adverse events leading to dose reduction (alectinib, 16%; crizotinib, 21%) or interruption (alectinib, 22%; crizotinib, 25%) were lower with alectinib than crizotinib,” the authors reported.

Adverse event rates were in most cases higher among patients receiving crizotinib, but anemia and increased blood bilirubin were both higher in patients in the alectinib study group (22% and 16%) than the crizotinib group (7% and 2%). Patients receiving alectinib also had higher rates of myalgia (16% vs 2%).