Safety profile and effectiveness of alectinib in the real-world surveillance study of 1251 Japanese patients with ALK-positive non-small cell lung cancer

Abstract

Background: Alectinib is a CNS penetrant and highly selective ALK inhibitor. The Japanese Risk Management Plan based on the phase I/II studies highlighted interstitial lung disease (ILD), liver function disorder, decreased neutrophil cell and white blood cell counts as identified risk in Japanese patients (pts). To investigate the safety and effectiveness of alectinib, including adverse drug reactions (ADR) of particular concern in the real world setting, a large scale surveillance funded by Chugai Pharmaceuticals has been implemented. This study is registered with the UMIN, number UMIN000014989. Methods: From Sep 2014 to June 2015 all pts with ALK-positive recurrent/advanced NSCLC treated with alectinib, were enrolled in the study. The observation period was 18 months, ADR were collected. Overall survival (OS) was also assessed. Results: By Jun 2015, a total of 1251 pts were registered. We analysed 1221 pts as the safety population. Baseline characteristics included: female (54%of population), median age (62 years), ECOG PS 3-4 (n=89) (7%), pts who received first line (18%), second line (32%) or third line or more (50%) treatments, pts who received crizotinib (63%), brain metastases (41%). The overall incidence of ADRs was 53.6%(mostly grade 1/2), the most common were laboratory tests abnormality (27.7%). ILD events were reported in 47 pts (3.8% of population), including grade 3 events in 8 pts and grade 4 events in 1 pt, in which the rate of recovery or improvement was 92%. Events of liver function disorder were reported in 242 pts (19.8%), including grade 3 events in 24 pts, and events of neutrophil cell and white blood cell decrease were reported in 93 pts (7.6%), including grade 3 events in 12 pts and grade 4 events in 2 pts, in which the rates of recovery or improvement were 83% and 93%, respectively. Median OS was not reached. Overall survival rate at 12 months and 18 months were 82.4%and 76.2%, respectively. Conclusions: These final data from this study in Japanese ALK-positive NSCLC pts provide an acceptable safety and effectiveness profile in the real-world setting. Alectinib was primarily one of the effective therapies for the treatment of ALK-positive NSCLC.