Clinical relevance of starting alectinib at a reduced dose in patients with ALK-positive non-small cell lung cancer.

8588 Background: Alectinib has been approved for Anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) at a lower dose (300 mg twice daily: b.i.d.) in Japan than the rest of the world (600 mg b.i.d.). To evaluate the clinical relevance of reducing the starting dose of alectinib, we compared the clinical outcomes of patients treated with one of the two doses. Methods: This study included patients with advanced ALK-positive NSCLC who received alectinib at Samsung Medical Center, Korea. The progression-free survival (PFS), overall survival, cumulative incidence of central nervous system (CNS) progression, and safety profiles were retrospectively reviewed and compared. Results: Among 306 patients, 32 and 274 received alectinib at either 300 or 600 mg b.i.d., respectively. The 300 mg group showed a slight but not significant advantage in PFS (HR 0.82, 95% CI 0.44-1.51, p=0.51) and overall survival (HR 0.51, 95% CI 0.20-1.21; p=0.13) compared with the 600 mg group. Interestingly, the superior survival outcome in the 300 mg group was remarkable in patients with lower body weight (≤60 kg). However, this advantage diminished at higher body weights (>60~75 kg or >75 kg). In addition, there was a slight tendency toward a higher incidence of CNS failure in the 300 mg group of patients with baseline brain metastasis (HR 1.76, 95% CI 0.53-5.8; p=0.36). Although the safety profiles were mostly mild and manageable in both groups, the 600 mg group showed more frequent adverse events than the 300 mg group and required dose reduction in 137 patients (50%). Conclusions: Alectinib at 300 mg b.i.d. seems an acceptable dose in patients with ALK-positive NSCLC even in areas outside Japan. Notably, our data favor 300 mg b.i.d. in patients with lower body weight and no baseline brain metastasis, considering the more tolerable safety profiles and the potential to reduce medical costs.