Safety and efficacy analysis of pembrolizumab dosing patterns in patients with advanced melanoma and non-small cell lung cancer

Aim To evaluate the impact of discrepancy between prescribed and recommended fixed 200 mg dose (P-F discrepancy) on immune-related adverse events (irAEs) and treatment efficacy in patients with advanced melanoma and NSCLC. Methods This retrospective study included 177 patients with advanced melanoma or non-small cell lung cancer (NSCLC) who received at least one cycle of single-agent pembrolizumab. We defined P-F discrepancy as the differences between prescribed pembrolizumab dose and 200 mg recommended dose, expressed in percentages. Our primary outcome was immune-related adverse events (irAEs), and our secondary outcomes included overall survival (OS) and progression free survival (PFS). Results The median P-F discrepancy was -21.5%, with the 25th and 75th percentile at -32% and -5.0% respectively. ROC curve analyses did not show any optimal cutoffs to prognosticate irAEs (AUC = 0.558 for all patients) or cancer mortality (AUC = 0.583 for melanoma; AUC = 0.539 for NSCLC) in either cancer type. Separate multivariable Cox analyses suggested no statistically significant association between P-F discrepancy and overall survival in patients with melanoma (HR 1.012, 95%CI 0.987-1.038, P = 0.362) or NSCLC (HR 0.998, 95%CI 0.978-1.019, P = 0.876). Conclusion There was no optimal pembrolizumab cut-off point to predict irAEs or treatment efficacy. We supported the use of weight-based pembrolizumab dosing, given the potential cost-saving and no differences in terms of irAEs or treatment efficacy in patients with advanced melanoma or NSCLC. Future studies on province- or national-level would be important to validate our findings.