A meta-analysis of pemetrexed-based doublet compared with pemetrexed alone for the second-line treatment of advanced non-small-cell lung cancer

Sun, Chengtao; Xu, Xianhua; Sheng, Wen‐Yung; Wang, X W; Wen, Shaoyan; Han, Junqing

doi:10.4149/bll_2014_048

Cited by 3 publications

(2 citation statements)

References 19 publications

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“…For instance, Klionsky et al reported that there was no significant difference in terms of thrombocytopenia between docetaxel and pemetrexed; however, Sun et al reported docetaxel caused a higher rate of thrombocytopenia. 38 , 39 In order to obtain a precise result, we only included large-sample Phase III trials for toxicity assessment. It also led to anemia compared with pemetrexed as the first-line treatment.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of docetaxel for advanced non-small-cell lung cancer: a meta-analysis of Phase III randomized controlled trials

He¹,

Wang²,

2015

OTT

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BackgroundSeveral clinical trials have performed risk–benefit analyses comparing docetaxel and pemetrexed or docetaxel and vinca alkaloid, but the efficacy and safety remain uncertain. The aim was to conduct a meta-analysis to compare the efficacy and safety of docetaxel and pemetrexed or docetaxel and vinca alkaloid for non-small-cell lung cancer.MethodsThis meta-analysis of Phase III randomized controlled trials was performed after searching PubMed, Embase, the Cochrane Library, and the ISI Web of Knowledge for randomized controlled trials. Outcome analyses were overall survival, progression-free survival, and overall response rate with 95% confidence intervals and major grade 3/4 toxicity.ResultsSeven eligible trials involving 2,080 patients were retrieved for analysis. Docetaxel enhanced progression-free survival and overall response rate compared with vinca alkaloid as first-line treatment (P<0.05). However, there was no difference between docetaxel and pemetrexed as both first-line and second-line treatment (P>0.05). With regard to the grade 3/4 toxicity, compared with pemetrexed, docetaxel led to higher neutropenia and febrile neutropenia (P<0.05), but there was no difference in non-hematological toxicity (P>0.05). Docetaxel led to a lower rate of anemia as first-line treatment (P<0.05). Moreover, docetaxel caused less grade 3/4 hematological and non-hematological toxicity compared with vinca alkaloid.ConclusionDocetaxel leads to a better result than vinca alkaloid in effectiveness and safety on patients with advanced non-small-cell lung cancer as first-line therapy. Docetaxel also causes lower toxicity as second-line therapy compared with vinca alkaloid. However, the differences in efficacy and safety between docetaxel and pemetrexed are not obvious. Further clinical study with more details, such as sex, age, histology, and so on, should be considered for illustrating the differences between these two drugs.

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Section: Discussionmentioning

confidence: 99%

Efficacy and safety of docetaxel for advanced non-small-cell lung cancer: a meta-analysis of Phase III randomized controlled trials

He¹,

Wang²,

2015

OTT

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“… 10 – 19 However, the conclusion drawn from these small-sample-size studies were inconsistent. Although previous meta-analyses conducted by Qi et al 20 and Sun et al 21 showed that the combination of pemetrexed and chemotherapy was not superior to single-agent pemetrexed as a second-line treatment for NSCLC, these analyses only included four and five studies, respectively, which is only ~50% of the available data. In addition, subgroup and sensitivity analyses were not performed, so the results might not be robust.…”

Section: Introductionmentioning

confidence: 99%

The efficacy and safety of pemetrexed-based doublet therapy compared to pemetrexed alone for the second-line treatment of advanced non-small-cell lung cancer: an updated meta-analysis

Zhong

Xiong

Shi

et al. 2015

DDDT

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BackgroundPemetrexed is currently recommended as the second-line treatment for patients with advanced non-small-cell lung cancer (NSCLC). However, it is unclear whether pemetrexed-based doublet therapy improves treatment efficacy and safety. Thus, this meta-analysis was performed to resolve this controversial question.MethodsElectronic databases, including PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched for relevant articles before April 2015. Hazard ratios (HRs) were used to estimate overall survival (OS) and progression-free survival (PFS), and odds ratios (ORs) were used to analyze the overall response rate (ORR) and grade ≥3 toxicities. Subgroup analysis, sensitivity analysis, and publication bias were also evaluated.ResultsA total of 2,519 patients from ten randomized controlled trials were included. Compared to pemetrexed alone, PFS and ORR significantly improved in the pemetrexed-based doublet group (HR, 0.86; 95% CI [confidence interval], 0.75–0.99; P=0.038; and OR, 1.98; 95% CI, 1.25–3.12; P=0.003, respectively). However, no statistically significant differences in OS were observed between groups (HR, 0.92; 95% CI, 0.83–1.02; P=0.132). In addition, subgroup analyses indicated that improved OS was only observed in nonsquamous NSCLC patients who received the combination of pemetrexed and erlotinib. An increasing incidence of grade ≥3 neutropenia and thrombocytopenia was observed in the pemetrexed-based doublet group.ConclusionAmong patients with advanced NSCLC, pemetrexed-based doublet treatment tended to be associated with improved PFS, ORR, and increased toxicity, but not OS.

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Wasted research when systematic reviews fail to provide a complete and up-to-date evidence synthesis: the example of lung cancer

Créquit

Trinquart

Yavchitz

et al. 2016

BMC Med

103

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BackgroundMultiple treatments are frequently available for a given condition, and clinicians and patients need a comprehensive, up-to-date synthesis of evidence for all competing treatments. We aimed to quantify the waste of research related to the failure of systematic reviews to provide a complete and up-to-date evidence synthesis over time.MethodsWe performed a series of systematic overviews and networks of randomized trials assessing the gap between evidence covered by systematic reviews and available trials of second-line treatments for advanced non-small cell lung cancer. We searched the Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, MEDLINE, EMBASE, and other resources sequentially by year from 2009 to March 2, 2015. We sequentially compared the amount of evidence missing from systematic reviews to the randomized evidence available for inclusion each year. We constructed cumulative networks of randomized evidence over time and evaluated the proportion of trials, patients, treatments, and treatment comparisons not covered by systematic reviews on December 31 each year from 2009 to 2015.ResultsWe identified 77 trials (28,636 patients) assessing 47 treatments with 54 comparisons and 29 systematic reviews (13 published after 2013). From 2009 to 2015, the evidence covered by existing systematic reviews was consistently incomplete: 45 % to 70 % of trials; 30 % to 58 % of patients; 40 % to 66 % of treatments; and 38 % to 71 % of comparisons were missing. In the cumulative networks of randomized evidence, 10 % to 17 % of treatment comparisons were partially covered by systematic reviews and 55 % to 85 % were partially or not covered.ConclusionsWe illustrate how systematic reviews of a given condition provide a fragmented, out-of-date panorama of the evidence for all treatments. This waste of research might be reduced by the development of live cumulative network meta-analyses.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-016-0555-0) contains supplementary material, which is available to authorized users.

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A meta-analysis of pemetrexed-based doublet compared with pemetrexed alone for the second-line treatment of advanced non-small-cell lung cancer

Cited by 3 publications

References 19 publications

Efficacy and safety of docetaxel for advanced non-small-cell lung cancer: a meta-analysis of Phase III randomized controlled trials

Efficacy and safety of docetaxel for advanced non-small-cell lung cancer: a meta-analysis of Phase III randomized controlled trials

The efficacy and safety of pemetrexed-based doublet therapy compared to pemetrexed alone for the second-line treatment of advanced non-small-cell lung cancer: an updated meta-analysis

Wasted research when systematic reviews fail to provide a complete and up-to-date evidence synthesis: the example of lung cancer

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