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

Background Pemetrexed is a key treatment for non-small-cell lung cancer (NSCLC), with its usage on the rise. However, due to treatment-related fatality in a patient with severe renal impairment observed during an initial clinical trial, such patients have been excluded from further studies. Consequently, there is limited data on the safety and efficacy of pemetrexed for these patients. This study aims to assess the use of pemetrexed in this patient group within a clinical setting. Methods We conducted a retrospective analysis of lung cancer patients treated with pemetrexed at Kyoto University Hospital from April 2008 to April 2023. Patients were categorized into groups receiving pemetrexed with platinum (n = 349) and pemetrexed-alone (n = 142) groups. Both groups were subdivided into creatinine clearance (CCr) > 45 and ≤ 45 subgroups, and safety and efficacy were compared between the subgroups. The chi-squared test was used to evaluate the correlation between renal impairment and adverse events. Univariate and logistic regression analyses identified independent risk factors for severe adverse events (SAEs) related to renal impairment. We also analyzed progression-free survival (PFS) and overall survival (OS) using log-rank tests. Results A significant increase in the incidence of grade ≥ 3 anemia was observed in the CCr ≤ 45 subgroups of both the platinum-concomitant and the pemetrexed-alone groups (p = 0.03 and p < 0.01, respectively). No significant differences were noted for other SAEs. Multivariate analysis showed that baseline hemoglobin levels were an independent predictor of grade ≥ 3 anemia across both treatment groups, alongside a baseline CCr ≤ 45 mL/min in the pemetrexed-alone group. No significant differences were observed in overall response rates, PFS, or OS between the CCr > 45 and CCr ≤ 45 subgroups in either treatment group. Conclusions While 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.