Meta-analysis of pemetrexed plus carboplatin doublet safety profile in first-line non-squamous non-small cell lung cancer studies

Objectives: This meta-analysis compared safety profiles (selected drug-related treatment-emergent adverse events [TEAEs]) of first-line pemetrexed plus carboplatin (PCb) area under the concentration-time curve 5 mg/min•mL (PCb5) or 6 mg/min•mL (PCb6), two widely used regimens in clinical practice for advanced non-squamous non-small cell lung cancer. Methods: All patients received pemetrexed 500 mg/m² every 21 days with either of two carboplatin doses for up to 4–6 cycles. Safety profiles of PCb doses were compared using three statistical analysis methods: frequency table analysis (FTA), generalized linear mixed effect model (GLMM), and the propensity score method. Efficacy outcomes of PCb5 and PCb6 regimens were summarized. Results: A total of 486 patients mainly from the US, Europe, and East Asia were included in the analysis; 22% (n = 105) received PCb5 in one trial and 78% (n = 381) received PCb6 in four trials. The FTA comparison demonstrated that PCb5 vs PCb6 was associated with a statistically significantly lower incidence of TEAEs, including all-grade thrombocytopenia, anemia, fatigue, and vomiting, and grade 3/4 thrombocytopenia. In the GLMM analysis, PCb5 patients were numerically less likely to experience all-grade and grade 3/4 neutropenia, anemia, and thrombocytopenia. The propensity score regression analysis showed PCb5 group patients were significantly less likely than PCb6 group patients to experience all-grade hematologic TEAEs and grade 3/4 thrombocytopenia and anemia. After applying propensity score 1:1 matching, FTA analysis showed that the PCb5 group had significantly less all-grade and grade 3/4 hematologic toxicities. Overall efficacy outcomes, including overall survival, progression-free survival, and response rate, were similar between the two carboplatin doses. Conclusions: Acknowledging the limitations of this meta-analysis of five trials, heterogeneous in patient’s characteristics and trial designs, the results show that the PCb5 regimen was generally associated with a better safety profile than PCb6 across three statistical approaches, with no apparent impact on survival outcomes.