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

Abstract

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.

Keywords:

• Pemetrexed
• carboplatin
• non-squamous non-small cell lung cancer
• safety
• efficacy

Transparency

Declaration of funding

The research of the manuscript was funded by Eli Lilly and Company (Indianapolis, IN).

Declaration of financial/other relationships

B.S.A., J.C., J.L., and W.J.J. are employed by Eli Lilly and Company and/or one of its subsidiaries, and are minor stockholders in Eli Lilly and Company. I.O., T.E.S., J.R.-P., and R.G.Z. report no conflicts of interest. W.H.W.S reports sponsorship by Roche, Eli Lilly, Amgen, and Merck, and service as a consultant/advisor for Roche, Eli Lilly, Amgen, and Merck. CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

The writing and editing of the manuscript were funded by Eli Lilly and Company (Indianapolis, IN), the manufacturers of pemetrexed. The authors thank Emily Cullinan and Noelle Gasco, of inVentiv Health Clinical, for their writing and editorial support.

Previous presentation

This abstract was presented at the European Society for Medical Oncology Congress; Madrid, Spain; September 26–30, 2014 (abstr 4968).