Association between lorlatinib serum concentration and adverse events and clinical impact of dose modification in ALK-rearranged NSCLC

The third-generation ALK inhibitor lorlatinib is associated with improvement of oncological outcomes among patients with ALK-rearranged non-small cell lung cancer (NSCLC) but also with adverse events (AEs), including hyperlipidemia and central nervous system disorders. A retrospective study at the National Cancer Hospital (Tokyo, Japan) investigated the association between lorlatinib serum concentration and AEs and the clinical impact of dose modification. Dose modification was required in 42% of patients. Lorlatinib serum concentrations were significantly higher in patients with grade ≥ 3 AEs than in those without grade ≥ 3 AEs (median 462 ng/ml versus 177 ng/ml; p<0.01). In patients with serial lorlatinib serum concentrations following dose modifications, lorlatinib serum concentrations were effectively reduced, facilitating the ongoing administration of lorlatinib. No significant difference was observed in the landmark analysis of progression-free survival between patients with dose modification within the first 16 weeks and those without (median 24.8 months versus 10.1 months; p=0.46). The authors conclude that dose modification of lorlatinib was associated with successful management of AEs and decreased serum concentrations of lorlatinib.