Dataset Information

Overall survival benefits for combining targeted therapy as second-line treatment for advanced non-small-cell-lung cancer: a meta-analysis of published data.

ABSTRACT:

Background

Combining targeted therapy has been extensively investigated in previously treated advanced non-small-cell lung cancer (NSCLC), but it is still unclear whether combining targeted therapy might offer any benefits against standard monotherapy with erlotinib. We thus performed a meta-analysis of randomized controlled trials to compare the efficacy and safety of combining targeted therapy versus erlotinib alone as second-line treatment for advanced NSCLC.

Methods

Several databases were searched, including Pubmed, Embase and Cochrane databases. The endpoints were overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and grade 3 or 4 adverse event (AEs). The pooled hazard ratio (HR) or odds ratio (OR), and 95% confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials.

Results

Eight eligible trials involved 2417 patients were ultimately identified. The intention to treatment (ITT) analysis demonstrated that combining targeted therapy significantly improved OS (HR 0.90, 95% CI: 0.82-0.99, p?=?0.024), PFS (HR 0.83, 95% CI: 0.72-0.97, p?=?0.018), and ORR (OR 1.35, 95% CI 1.01-1.80, P?=?0.04). Sub-group analysis based on phases of trials, EGFR-status and KRAS status also showed that there was a tendency to improve PFS and OS in combining targeted therapy, except that PFS for patients with EGFR-mutation or wild type KRAS favored erlotinib monotherapy. Additionally, more incidence of grade 3 or 4 rash, fatigue and hypertension were observed in combining targeted therapy.

Conclusions

With the available evidence, combining targeted therapy seems superior over erlotinib monotherapy as second-line treatment for advanced NSCLC. More studies are still needed to identify patients who will most likely benefit from the appropriate combining targeted therapy.

SUBMITTER: Qi WX

PROVIDER: S-EPMC3568141 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Overall survival benefits for combining targeted therapy as second-line treatment for advanced non-small-cell-lung cancer: a meta-analysis of published data.

Qi Wei-Xiang WX Wang Qiong Q Jiang Yan-Ling YL Sun Yuan-Jue YJ Tang Li-Na LN He Ai-Na AN Min Da-Liu DL Lin Feng F Shen Zan Z Yao Yang Y

PloS one 20130208 2

<h4>Background</h4>Combining targeted therapy has been extensively investigated in previously treated advanced non-small-cell lung cancer (NSCLC), but it is still unclear whether combining targeted therapy might offer any benefits against standard monotherapy with erlotinib. We thus performed a meta-analysis of randomized controlled trials to compare the efficacy and safety of combining targeted therapy versus erlotinib alone as second-line treatment for advanced NSCLC.<h4>Methods</h4>Several da ...[more]

PMID: 23409011

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Project description:ContextCurrent guidelines suggest several targeted therapies (TTs) and immunotherapies (ITs) in the treatment of advanced or metastatic renal cell carcinoma (mRCC). Ideal sequencing of these treatments is unclear.ObjectiveThe primary objective was to evaluate the overall survival (OS) data of the treatments approved for mRCC. Secondary objectives included evaluating other signs of efficacy and adverse events.Evidence acquisitionWe reviewed the current Food and Drug Administration-approved treatments for mRCC. Trials associated with approval were reviewed. We also included pre- and postapproval publications when appropriate.Evidence synthesisThere is minimal evidence supporting OS benefit for the nine approved TTs. They result in adverse events and are a considerable economic burden. For these reasons, their future role in mRCC treatment should be re-evaluated, given the emergence of IT that have demonstrated OS benefits. Accumulating long-term survival data with high-dose interleukin-2 treatment suggests that this older treatment could still be considered for eligible patients. Checkpoint inhibitors have shown promising OS and durable responses; as such, the high cost of treatment might be justified. However, the available evidence does not suggest that adding TT to IT would increase efficacy over IT alone, but would add toxicity.ConclusionsTrial data supporting OS benefit are much stronger for ITs than for TTs. Combining checkpoint inhibitors with TTs has not been shown to produce better OS than checkpoint inhibitors alone, while more adverse events are present. Granting drug approvals based on efficacy without demonstrated OS benefit should be revisited.Patient summaryApproved treatments for metastatic kidney cancer include targeted and immune-based therapies. The former commonly produces temporary tumour shrinkage, but survival benefits are unclear. All approved immunotherapies have increased survival, and a proportion of patients appear cured.

Project description:IntroductionAdvanced gastric cancer (AGC) is one of the most common forms of cancer and remains difficult to cure. There is currently no recommended therapy for second-line AGC in the UK despite the availability of various interventions. This paper aims to compare different interventions for treatment of second-line AGC using more complex methods to estimate relative efficacy, fitting various parametric models and to compare results to those published adopting conventional methods of synthesis.MethodsSeven studies were identified in an existing literature review evaluating seven comparators, which formed a connected network of evidence. Citations were limited to randomised controlled trials in previously-treated AGC patients. Evidence quality was assessed using the Cochrane Collaboration's tool. Studies were assessed for the availability of Kaplan-Meier curves for overall survival. Individual patient data (IPD) were recreated using digitisation software along with a published algorithm in R. The data were analysed using multi-dimensional network meta-analysis (NMA) methods. A series of parametric models were fitted to the pseudo-IPD. Both fixed and random-effects models were fitted to explore long-term survival prospects based on extrapolation methods and estimated mean survival.ResultsRelative efficacy estimates were compared to those previously reported, which utilised conventional NMA methods. Results presented were consistent within findings from other publications and identified ramucirumab plus paclitaxel as the best treatment; however, all the treatments assessed were associated with poor survival prospects with mean survival estimates ranging from 5.0 to 12.7 months.ConclusionWhilst the approach adopted in this paper does not adjust for differences in trial patient populations and is particularly data-intensive, use of such sophisticated methods of evidence synthesis may be more informative for subsequent cost-effectiveness modelling and may have greater impact when considering an indication where observed data is particularly immature or survival prospects are more positive, which may then lead to more informative decision-making for drug reimbursement.

Dataset Information

Overall survival benefits for combining targeted therapy as second-line treatment for advanced non-small-cell-lung cancer: a meta-analysis of published data.

Background

Methods

Results

Conclusions

Publications

Overall survival benefits for combining targeted therapy as second-line treatment for advanced non-small-cell-lung cancer: a meta-analysis of published data.

Similar Datasets

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