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Effectiveness and safety of pemetrexed-based doublet versus pemetrexed alone as second-line treatment for advanced non-small-cell lung cancer: a systematic review and meta-analysis

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Abstract

Background

To compared pemetrexed-based doublet with single-agent pemetrexed as second-line treatment for advanced non-small-cell lung cancer

Methods

We systematically searched for randomized clinical trials that compared pemetrexed-based doublet with single-agent pemetrexed in patients with histologically proven non-small-cell lung cancer. The primary end point was overall survival. Secondary end points were progression-free survival, overall response rate and grade 3 or 4 toxicity. Data were extracted from the studies by 2 independent reviewers. The meta-analysis was performed by Stata version 10.0 software (Stata Corporation, College Station, Texas, USA).

Results

Five randomized clinical trials (totally 1,186 patients) were eligible. Meta-analysis showed that there was significant improvement in PFS (HR 0.82, 95% CI 0.71–0.95, P = 0.007) and overall response rate (OR 2.39, 95% CI 1.58–3.62, P = 0.000) in pemetrexed-based doublet group, compared with pemetrexed alone, though the pooled HR for overall survival (HR 0.89, 95% CI 0.76–1.04; P = 0.129) showed no significant difference between the two groups. However, there were more incidences of grade 3 or 4 neutropenia (OR 2.3, 95% CI 1.4–3.77, P = 0.001), thrombocytopenia (OR 6.41, 95% CI 2.57–16.0, P = 0.000), and leucopenia (OR 2.45, 95% CI 1.13–5.34, P = 0.024) in pemetrexed-based doublet group. With regard to the risk of grade 3 or 4 anemia (OR 0.71, 95% CI 0.17–2.91, P = 0.629) and fatigue (OR 1.47, 95% CI 0.92–2.35, P = 0.104), there was no significant difference between the two groups.

Conclusion

Pemetrexed-based doublet therapy didn’t gain any benefit in survival but significantly improved PFS and better ORR compared with single-agent pemetrexed as second-line therapy for advanced non-small-cell lung cancer. However, more incidences of grade 3 or 4 neutropenia, thrombocytopenia, and leucopenia were observed in pemetrexed-based doublet group.

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We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence this work.

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Correspondence to Yang Yao.

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Qi, WX., Tang, LN., He, AN. et al. Effectiveness and safety of pemetrexed-based doublet versus pemetrexed alone as second-line treatment for advanced non-small-cell lung cancer: a systematic review and meta-analysis. J Cancer Res Clin Oncol 138, 745–751 (2012). https://doi.org/10.1007/s00432-012-1155-9

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  • DOI: https://doi.org/10.1007/s00432-012-1155-9

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