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
ABSTRACT To compared pemetrexed-based doublet with single-agent pemetrexed as second-line treatment for advanced non-small-cell lung cancer
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).
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.
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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ABSTRACT: Abstract Objectives: To compare the effects of adding targeted agents to standard second-line chemotherapy with a single-agent (pemetrexed or docetaxel) in patients with advanced NSCLC, a meta-analysis of all relevant randomized controlled trials was performed and overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) were assessed. Patients and methods: The PubMed, Embase databases and the Cochrane Central Register of Controlled Trials were searched for relevant publications reporting randomized controlled trials between January 2000 and December 2013. Hazard ratios (HRs) with their 95% confidence intervals (CIs), or data for calculating HRs with 95% CI were derived. Results: Fourteen trials with a total of 6,922 patients were included in this meta-analysis. Compared with chemotherapy, combination therapy did not improve OS (HR=0.95; 95% CI, 0.90-1.01; P=0.081) but improved PFS (HR=0.83; 95% CI, 0.78-0.87; P=0.000). Survival outcomes did not differ significantly among trials. Combination therapy significantly increased ORR (RR=1.83; 95% CI, 1.59-2.127; P=0.000) and DCR (RR=1.18; 95% CI, 1.13-1.23, P= 0.000). Sub-analysis indicated that adding targeted therapy to chemotherapy significantly prolonged OS in patients with non-squamous NSCLC (HR=0.87; 95% CI, 0.87-0.97; P=0.009). Patients treated with combination therapy had an increased incidence of grade 3 or greater diarrhea (RR=1.96; 95% CI, 1.37-2.81; P=0.000), neutropenia (RR=1.27, 95% CI, 1.14-1.61; P=0.000) and thrombocytopenia (RR=4.21, 95% CI, 1.87-9.51; P=0.001). This meta-analysis has limitations of not using individual patient data and heterogeneity among the included trials. Conclusions: In the second-line treatment of advanced NSCLC, the combination of targeted therapy and chemotherapy significantly increased response rates and progression-free survival, but did not improve overall survival and was more toxic.Current Medical Research and Opinion 04/2014; 30(11). DOI:10.1185/03007995.2014.909392 · 2.37 Impact Factor
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ABSTRACT: Introduction: Non-small cell lung cancer (NSCLC) is a major cause of cancer-related death worldwide. Although advanced NSCLC is still incurable, various anti-neoplastic agents have become available for the treatment of this disease. Pemetrexed , a multi-target folate antagonist, has improved the survival of non-squamous NSCLC patients. Currently, pemetrexed is approved for first-line treatment in combination with a platinum derivate, for second-line treatment as a single agent and, more recently, as maintenance treatment after first-line chemotherapy. Areas covered: The authors analyzed the state of the art of pemetrexed through a review of the literature. Clinical trials and meta-analyses involving pemetrexed in NSCLC were evaluated. Pemetrexed improved survival of non-squamous NSCLC in first-line, maintenance, and second-line treatments; this benefit is limited to non-squamous histology. Because pemetrexed has become part of the standard of care, current clinical trials are designed to compare it to other investigational combinations. Limited data on resectable disease are available, and additional clinical trials are being conducted. Expert opinion: Pemetrexed has shown effectiveness and a favorable toxicity profile. Histology-driven indications and the relationship of pemetrexed with thymidylate synthase expression suggest that a more precise definition of predictive biomarkers could be further investigated.Expert Opinion on Pharmacotherapy 05/2013; DOI:10.1517/14656566.2013.802774 · 3.09 Impact Factor
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ABSTRACT: Platinum-based chemoradiotherapy (CRT) is a standard front-line treatment for locally advanced non-small cell lung cancer (NSCLC). However, no clinical trials have compared the efficacy and toxicity of platinum combination and docetaxel as subsequent re-challenge chemotherapies after cancer recurrence following CRT. This study aimed to evaluate the efficacy and toxicity of platinum combination chemotherapy versus docetaxel monotherapy in NSCLC patients previously treated with platinum-based CRT. From September 2002 to December 2009, at three participating institutions, 24 patients with locally advanced NSCLC, who had previously received platinum-based CRT, were treated with platinum combination re-challenge therapy, whereas 61 received docetaxel monotherapy. We reviewed their medical charts to evaluate patient characteristics and data regarding treatment response, survival, and toxicity. The response rates were 16.7% and 6.6% in the platinum combination chemotherapy and docetaxel monotherapy groups, respectively (p = 0.09), whereas disease control rates were 58.3% and 57.4%, respectively (p = 0.82). Progression-free survival was similar between the two groups (median, 4.2 vs. 2.3 months; hazard ratio [HR] = 0.81; 95% confidence interval [CI] = 0.51-1.29; p = 0.38), as was overall survival (median, 16.5 vs. 13.0 months; HR = 0.82; 95% CI = 0.47-1.41; p = 0.47). The incidence and severity of toxicity was also similar between the two groups. Hematological toxicity, particularly leukopenia and neutropenia, was more frequent in the docetaxel group. Our results indicated that platinum combination re-challenge was equivalent to docetaxel for relapsed patients previously treated with platinum-based CRT.SpringerPlus 01/2015; 4:152. DOI:10.1186/s40064-015-0929-3