The efficacy of ceritinib for alk-rearranged non-small cell lung cancer previously treated with alectinib - An analysis of Japanese and global Phase I studies

Objective. We analyzed the efficacy of ceritinib in patients with ALK-rearrangement non-small cell lung cancer (ALK + NSCLC) who had a history of ALK inhibitor (ALKi) therapy including alectinib. Methods. The efficacy and safety of ceritinib in patients with ALK + NSCLC was analyzed in a Japanese phase I study. The efficacy of ceritinib was also analyzed in patients with a history of alectinib therapy in a Japanese phase I study and ASCEND-1. Results. In the Japanese phase I study, the rate of major serious adverse events was increased with ALT. The overall response rate (ORR) and disease control rate (DCR) in patients administered ceritinib 750 mg/day, the maximum tolerated and recommended dose, were 37.5% (3/8) and 75.0% (6/8), respectively. The ORR in patients who had a history of ALKi therapy was 52.9% (9/17, all patients showed a partial response [PR]), and the progression-free survival was longer than 4.2 months in these responders. An ALK secondary mutation (L1196M, 11171, I1171T) was reported in three of the nine patients who showed PR. In the Japanese phase I study and ASCEND-1, PR was confirmed in 41.7% (5/12) of patients who had a history of alectinib therapy. Conclusion. Ceritinib may be a new treatment option for ALK+NSCLC patients with a history of alectinib therapy.