Safety and efficacy of pemetrexed for patients with non-small cell lung cancer in the setting of renal impairment: a retrospective study

Abstract

BACKGROUND: Pemetrexed is a key treatment for non-small-cell lung cancer (NSCLC), and its usage is increasing. However, owing to treatment-related fatality in a patient with severe renal impairment observed during an initial clinical trial, such patients were excluded from further studies. Consequently, data on the safety and efficacy of pemetrexed in these patients are limited. This study aimed to assess the use of pemetrexed in this patient group in a clinical setting. METHODS: We conducted a retrospective analysis of patients with lung cancer treated with pemetrexed at Kyoto University Hospital from April 2008 to April 2023. The patients were categorized into two groups: those who received pemetrexed with platinum derivatives (n = 349) and those who received pemetrexed alone (n = 142). Both groups were further divided into creatinine clearance (CCr) > 45 and ≤ 45 mL/min subgroups, and safety and efficacy were compared between the subgroups. The correlation between renal impairment and adverse events was evaluated through chi-square test. Univariate and logistic regression analyses were used to identify the independent risk factors for severe adverse events (SAEs) related to renal impairment. We also analyzed the progression-free survival (PFS) and overall survival (OS) using log-rank test. RESULTS: A significant increase in the incidence of grade 3 or higher anemia was observed in the CCr ≤ 45 mL/min subgroups of both the platinum-concomitant and pemetrexed-alone groups (p = 0.03 and p < 0.01, respectively). No significant differences were observed in other SAEs. Multivariate analysis showed that baseline hemoglobin levels were an independent predictor of grade 3 or higher anemia across both treatment groups, alongside a baseline CCr ≤ 45 mL/min in the pemetrexed-alone group. No significant differences were observed in the overall response rate, PFS, or OS between the CCr > 45 and CCr ≤ 45 mL/min subgroups in either treatment group. CONCLUSIONS: Although severe anemia was more common in patients with renal impairment, the efficacy of treatment did not differ, indicating that pemetrexed remains a viable treatment option for this population with proper management.