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

Isamu Okamoto, Wolfgang H.W. Schuette, Thomas E. Stinchcombe, José Rodrigues-Pereira, Belén San Antonio, Jian Chen, Jingyi Liu, William J. John, Ralph G. Zinner

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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.

Original languageEnglish
Pages (from-to)937-941
Number of pages5
JournalCurrent Medical Research and Opinion
Volume33
Issue number5
DOIs
Publication statusPublished - May 4 2017

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Pemetrexed
Carboplatin
Non-Small Cell Lung Carcinoma
Meta-Analysis
Safety
Propensity Score
Anemia
Thrombocytopenia
Survival
Far East
Neutropenia
Disease-Free Survival
Vomiting
Fatigue
Therapeutics
Survival Rate
Regression Analysis
Incidence

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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Meta-analysis of pemetrexed plus carboplatin doublet safety profile in first-line non-squamous non-small cell lung cancer studies. / Okamoto, Isamu; Schuette, Wolfgang H.W.; Stinchcombe, Thomas E.; Rodrigues-Pereira, José; San Antonio, Belén; Chen, Jian; Liu, Jingyi; John, William J.; Zinner, Ralph G.

In: Current Medical Research and Opinion, Vol. 33, No. 5, 04.05.2017, p. 937-941.

Research output: Contribution to journalArticle

Okamoto, I, Schuette, WHW, Stinchcombe, TE, Rodrigues-Pereira, J, San Antonio, B, Chen, J, Liu, J, John, WJ & Zinner, RG 2017, 'Meta-analysis of pemetrexed plus carboplatin doublet safety profile in first-line non-squamous non-small cell lung cancer studies', Current Medical Research and Opinion, vol. 33, no. 5, pp. 937-941. https://doi.org/10.1080/03007995.2017.1297701
Okamoto, Isamu ; Schuette, Wolfgang H.W. ; Stinchcombe, Thomas E. ; Rodrigues-Pereira, José ; San Antonio, Belén ; Chen, Jian ; Liu, Jingyi ; John, William J. ; Zinner, Ralph G. / Meta-analysis of pemetrexed plus carboplatin doublet safety profile in first-line non-squamous non-small cell lung cancer studies. In: Current Medical Research and Opinion. 2017 ; Vol. 33, No. 5. pp. 937-941.
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AU - Rodrigues-Pereira, José

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N2 - 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.

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