Alectinib (ALC) versus crizotinib (CRZ) in ALK-inhibitor naive ALK-positive non-small cell lung cancer (ALK+ NSCLC): Primary results from the J-ALEX study

Alectinib (ALC) showed promising efficacy and tolerability in the phase 1/2 study (AF-001JP).^1,2 Nokihara and colleagues conducted a randomized open-label phase 3 trial (J-ALEX study) to prove superior progression-free survival (PFS) of ALC to crizotinib (CRZ) in ALK-positive non–small-cell lung cancer (NSCLC) patients without prior ALK inhibitor treatment.³ ALK-positive NSCLC patients were randomized 1:1 either to receive ALC (300 mg twice daily) or CRZ (250 mg twice daily) and stratified by Eastern Cooperative Oncology Group Performance Status (PS; 0/1 vs 2), treatment line (first vs second), and clinical stage (IIIB/IV vs recurrence). Treatment on both arms was continued until disease progression or unacceptable toxicity. The primary end point was PFS according to a blinded independent review board. Secondary end points included overall survival, objective response rate, and safety. A total of 207 patients were enrolled at 41 centers in Japan; 98%, 73%, and 64% of the patients were PS 0-1, stage IV, and first line, respectively. On an interim analysis, the Independent Data Monitoring Committee recommended the release of study data because the superiority in PFS had been demonstrated. The PFS hazard ratio of the ALC arm to the CRZ arm was 0.34 (99.6826% confidence interval [CI], 0.17-0.70, stratified log-rank P<0.0001). Median PFS was not reached (95% CI, 20.3-Not Estimated) in the ALC arm compared with 10.2 months (95% CI, 8.2-12.0) in the CRZ arm. In the ALC arm, constipation was the only adverse event (AE) reported in >30% of patients, whereas in the CRZ arm, nausea (74%), diarrhea (73%), vomiting (59%), visual disturbance (55%), dysgeusia (52%), constipation (46%), alanine aminotransferase elevation (32%), and aspartate aminotransferase elevation (31%) were observed. Grade 3-4 AEs occurred with greater frequency in the CRZ arm (ALC arm, 27%, vs CRZ arm, 51%). There were no treatment-related deaths in either arm. The authors conclude that ALC demonstrated significantly prolonged PFS compared with CRZ and was better tolerated with a favorable AE profile.

1. Seto T, et al. Lancet Oncol. 2013;14:590-598.
2. Takeuchi K, et al. Ann Oncol. 2016;27:185-192.
3. Nokihara H, et al. ASCO 2016. Abstract 9008.