New data from an interim analysis of the head-to-head, open-label, phase 3, Japanese study J-ALEX, show that alectinib (Alecensa) significantly improved progression-free survival (PFS) compared with crizotinib (Xalkori) in the frontline setting, according to Hiroshi Nokihara, MD, PhD, of the National Cancer Center Hospital, Tokyo, Japan.
“Based on these results, we believe that alectinib is the new standard first-line therapy for ALK-positive NSCLC,” Dr Nokihara said recently.
Alectinib, an oral anaplastic lymphoma kinase (ALK) inhibitor, was approved in December 2015 for advanced, ALK-positive non–small-cell lung cancer (NSCLC) that progressed after crizotinib therapy.
Overall, 207 Japanese patients with advanced or recurrent NSCLC and ALK mutation who had never received an ALK inhibitor were randomized to alectinib 300 mg twice daily or to crizotinib 250 mg twice daily, with a follow-up of 12 months in the alectinib group and 12.2 months in the crizotinib group. Treatment continued until disease progression or unacceptable toxicity. The primary end point was median PFS.
At baseline, 27.9% of patients in the crizotinib group had brain metastases compared with 13.6% in the alectinib group; other baseline characteristics were similar between the 2 groups.
The median PFS was significantly superior with alectinib versus crizotinib: at the time of data analysis, median PFS had not been reached with alectinib versus 10.2 months with crizotinib.
In patients with brain metastases at baseline, the hazard ratio for PFS was 0.08 with alectinib versus crizotinib.
Overall, 26.2% of patients in the alectinib group had grade 3 or 4 adverse events versus 51.9% in the crizotinib group. Treatment interruption because of adverse events was less common with alectinib (29.1%) than with crizotinib (74.0%).
The only adverse event reported in >30% of patients in the alectinib group was constipation; nausea, diarrhea, vomiting, visual disturbance, dysgeusia, constipation, elevation in alanine aminotransferase levels, and elevation in aspartate aminotransferase levels each occurred in >30% of patients.
Overall, 8 patients in each treatment group withdrew from the study because of interstitial lung disease.