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Journal of Comparative Effectiveness... Aug 2020To perform indirect treatment comparisons of entrectinib versus alternative fusion-positive non-small cell lung cancer treatments. Relevant studies with crizotinib... (Comparative Study)
Comparative Study
To perform indirect treatment comparisons of entrectinib versus alternative fusion-positive non-small cell lung cancer treatments. Relevant studies with crizotinib and chemotherapy as comparators of interest identified by systematic literature review were selected for matching-adjusted indirect comparison by feasibility assessment. Matching was based on known prognostic/predictive factors and scenario analyses were used for unreported confounders in comparator trials. Entrectinib yielded significantly better responses versus crizotinib in all scenarios (odds ratio [OR]: 2.43-2.74). Overall survival (hazard ratio: 0.47-0.61) and adverse event-related discontinuation (OR: 0.79-0.90) favored entrectinib. Progression-free survival was similar across treatments, except in one scenario. These results suggested improved outcomes with entrectinib versus crizotinib/chemotherapy and may help to make better informed treatment decisions.
Topics: Antineoplastic Agents; Benzamides; Carcinoma, Non-Small-Cell Lung; Crizotinib; Humans; Indazoles; Lung; Lung Neoplasms; Protein-Tyrosine Kinases; Proto-Oncogene Proteins
PubMed: 32648475
DOI: 10.2217/cer-2020-0063 -
BMJ (Clinical Research Ed.) Oct 2019To compare the efficacy and safety of first line treatments for patients with advanced epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC). (Meta-Analysis)
Meta-Analysis
Efficacy and safety of first line treatments for patients with advanced epidermal growth factor receptor mutated, non-small cell lung cancer: systematic review and network meta-analysis.
OBJECTIVE
To compare the efficacy and safety of first line treatments for patients with advanced epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC).
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
PubMed, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and several international conference databases, from inception to 20 May 2019.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Published and unpublished randomised controlled trials comparing two or more treatments in the first line setting for patients with advanced EGFR mutated NSCLC were included in a bayesian network meta-analysis. Eligible studies reported at least one of the following clinical outcome measures: progression free survival, overall survival, objective response rate, and adverse events of grade 3 or higher.
RESULTS
18 eligible trials involved 4628 patients and 12 treatments: EGFR tyrosine kinase inhibitors (TKIs; osimertinib, dacomitinib, afatinib, erlotinib, gefitinib, and icotinib), pemetrexed based chemotherapy, pemetrexed free chemotherapy, and combination treatments (afatinib plus cetuximab, erlotinib plus bevacizumab, gefitinib plus pemetrexed based chemotherapy, and gefitinib plus pemetrexed). Consistent with gefitinib plus pemetrexed based chemotherapy (hazard ratio 0.95, 95% credible interval 0.72 to 1.24), osimertinib showed the most favourable progression free survival, with significant differences versus dacomitinib (0.74, 0.55 to 1.00), afatinib (0.52, 0.40 to 0.68), erlotinib (0.48, 0.40 to 0.57), gefitinib (0.44, 0.37 to 0.52), icotinib (0.39, 0.24 to 0.62), pemetrexed based chemotherapy (0.24, 0.17 to 0.33), pemetrexed free chemotherapy (0.16, 0.13 to 0.20), afatinib plus cetuximab (0.44, 0.28 to 0.71), and gefitinib plus pemetrexed (0.65, 0.46 to 0.92). Osimertinib and gefitinib plus pemetrexed based chemotherapy were also consistent (0.94, 0.66 to 1.35) in providing the best overall survival benefit. Combination treatments caused more toxicity in general, especially erlotinib plus bevacizumab, which caused the most adverse events of grade 3 or higher. Different toxicity spectrums were revealed for individual EGFR-TKIs. Subgroup analyses by the two most common EGFR mutation types indicated that osimertinib was associated with the best progression free survival in patients with the exon 19 deletion, and gefitinib plus pemetrexed based chemotherapy was associated with the best progression free survival in patients with the Leu858Arg mutation.
CONCLUSIONS
These results indicate that osimertinib and gefitinib plus pemetrexed based chemotherapy were associated with the best progression free survival and overall survival benefits for patients with advanced EGFR mutated NSCLC, compared with other first line treatments. The treatments resulting in the best progression free survival for patients with the exon 19 deletion and Leu858Arg mutations were osimertinib and gefitinib plus pemetrexed based chemotherapy, respectively.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42018111954.
Topics: Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Humans; Mutation; Network Meta-Analysis
PubMed: 31591158
DOI: 10.1136/bmj.l5460 -
Lung Cancer (Amsterdam, Netherlands) Sep 2019Platinum-based chemotherapy is the mainstay of first-line (1L) therapy for advanced non-small cell cancer (NSCLC). The objective of this study was to evaluate the... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Platinum-based chemotherapy is the mainstay of first-line (1L) therapy for advanced non-small cell cancer (NSCLC). The objective of this study was to evaluate the relative efficacy, safety, and health-related quality of life (HRQoL) of carboplatin- versus cisplatin-based chemotherapy in 1L NSCLC.
MATERIALS AND METHODS
A meta-analysis by the Cochrane group (2013) was updated. Systematic searches of CENTRAL, Medline, Embase, Latin American and Caribbean Health Sciences database, clinicaltrials.gov and conference proceedings were conducted to include randomized controlled trials (RCTs) published between 2013-January 2018 which compared carboplatin and cisplatin combined with: gemcitabine, vinorelbine, docetaxel, paclitaxel, irinotecan, or pemetrexed. Endpoints included overall survival (OS), one-year OS, objective response rate (ORR), grade 3/4 drug-related toxicities, and HRQoL.
RESULTS
Twelve RCTs (2,048 patients) were identified from 4,139 records for inclusion in the meta-analysis. There were no significant differences in OS (hazards ratio [HR]: 1.08, 95% confidence interval [CI]: 0.96, 1.21) and one-year OS (relative risk [RR]: 0.97, CI: 0.89, 1.07) between carboplatin- and cisplatin-based chemotherapy. A small effect on ORR favouring cisplatin was detected (RR = 0.88; CI: 0.78, 0.99). Differences in drug-related toxicities were observed between carboplatin- and cisplatin-based chemotherapy for thrombocytopenia, anaemia, neurotoxicity, and the risk of nausea/vomiting. Three RCTs comparing HRQoL between carboplatin- and cisplatin-based chemotherapy found no significant differences.
CONCLUSIONS
This updated evidence base corroborates findings of previous meta-analyses showing no difference in OS between carboplatin- and cisplatin-based chemotherapy, despite a slight benefit in ORR for cisplatin. Toxicity profiles should be considered alongside patients' comorbidities in the choice of therapy.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Cisplatin; Humans; Lung Neoplasms; Odds Ratio; Publication Bias; Quality of Life; Treatment Outcome
PubMed: 31446995
DOI: 10.1016/j.lungcan.2019.07.010 -
Radiation Oncology (London, England) Mar 2019It remains unknown which is the most preferable regimen used concurrently with thoracic radiation for locally advanced non-small cell lung cancer (NSCLC). We performed a... (Comparative Study)
Comparative Study Meta-Analysis
Comparative efficacy and safety for different chemotherapy regimens used concurrently with thoracic radiation for locally advanced non-small cell lung cancer: a systematic review and network meta-analysis.
BACKGROUND
It remains unknown which is the most preferable regimen used concurrently with thoracic radiation for locally advanced non-small cell lung cancer (NSCLC). We performed a network meta-analysis to address this important issue.
METHODS
PubMed, Embase, Cochrane Library, Web of Science and major international scientific meetings were searched for relevant randomized controlled trials (RCTs). Overall survival (OS) data was the primary outcome of interest, and progression-free survival (PFS), and serious adverse events (SAEs) were the secondary outcomes of interests, reported as hazard ratio (HR) or odds ratio (OR) and 95% confidence intervals (CIs).
RESULTS
14 RCTs with a total of 2975 patients randomized to receive twelve categories of treatments were included in the meta-analysis. Direct comparison meta-analysis showed that etoposide-cisplatin (EP) was more effective than paclitaxel-cisplatin/carboplatin (PC) in terms of OS (HR = 0.85, 95% CI: 0.77-0.94) and PFS (HR = 0.66, 95% CI: 0.47-0.95). In network meta-analysis, all regimen comparisons did not produce statistically significant differences in survival. Based on treatment ranking of OS and the benefit-risk ratio, S-1-cisplatin (SP) was likely to be the most preferable regimen for its best efficacy and low risk of causing SAEs. Uracil/tegafur-cisplatin (UP) and pemetrexed-cisplatin/carboplatin (PP) were ranked the second and third respectively. Gemcitabine-cisplatin (GP) and PC + Cetuximab (PC-Cet) appeared to be the worst and second-worst regimens for their poor efficacy and poor tolerability.
CONCLUSIONS
Based on efficacy and tolerability, SP is likely to be the most preferable regimen used concurrently with thoracic radiation for locally advanced NSCLC, followed by UP and PP. Further direct head-to-head studies are needed to confirm these findings.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Humans; Lung Neoplasms; Network Meta-Analysis; Prognosis; Thoracic Neoplasms
PubMed: 30925881
DOI: 10.1186/s13014-019-1239-7 -
The European Journal of Health... Jul 2019To review and assess the quality of the available evidence on the cost-effectiveness of erlotinib in the first-line treatment of advanced non-small cell lung cancer...
OBJECTIVE
To review and assess the quality of the available evidence on the cost-effectiveness of erlotinib in the first-line treatment of advanced non-small cell lung cancer (NSCLC).
METHODS
A systematic review was conducted to identify full-text original economic evaluations of erlotinib in the first-line treatment of advanced NSCLC written in English and published from the year 2000 onwards. Study characteristics and results were recorded and compared. The quality of the studies was assessed by the Quality of Health Economic Studies (QHES) questionnaire.
RESULTS
Eleven out of 130 papers were chosen for this review. Comparative regimens consisted of a best supportive care, reverse strategy, bevacizumab, cisplatin plus pemetrexed, carboplatin plus gemcitabine or gefitinib. The methods most used in these studies were modeling and sensitivity analysis and cost-effectiveness analysis. All of the studies evaluated direct costs and used quality-adjusted life-year (QALY) and life-years gained (LYG) as outcome, with 3% and 3.5% discount rate. The studies assigned ICER that ranged from dominant to I$305,510.31/QALY and from I$31,209.55/LYG to I$66,540.20/LYG. Based on the willingness to pay threshold, seven studies concluded that erlotinib was cost-effective, two studies showed that erlotinib was cost-effective on specific patients with certain conditions, and two studies comparing erlotinib with reverse strategy did not find a difference in cost-effectiveness. The high quality of these studies was confirmed using the QHES tool: the mean score was 75.77 out of 100 (SD 9.38).
CONCLUSION
Most of these high-quality studies suggested that erlotinib was cost-effective in the first-line treatment of advanced NSCLC.
Topics: Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Economics, Pharmaceutical; Erlotinib Hydrochloride; Humans; Lung Neoplasms
PubMed: 30840166
DOI: 10.1007/s10198-019-01040-7 -
Immunotherapy Apr 2019A systematic review and network meta-analysis were conducted to evaluate the efficacy of pembrolizumab + pemetrexed + platinum relative to other regimens in... (Meta-Analysis)
Meta-Analysis
AIM
A systematic review and network meta-analysis were conducted to evaluate the efficacy of pembrolizumab + pemetrexed + platinum relative to other regimens in metastatic nonsquamous non-small-cell lung cancer (NSq-NSCLC).
PATIENTS & METHODS
Eligible studies evaluated first-line regimens in NSq-NSCLC patients without known targetable mutations. Relative treatment effects were synthesized with random effects proportional hazards Bayesian network meta-analyses.
RESULTS
The hazard ratio (HR) for overall survival (OS) for pembrolizumab + pemetrexed + platinum was statistically significant over all platinum-doublet (HR range: 0.42-0.61), platinum-doublet + bevacizumab (HR range: 0.44-0.53) and platinum-doublet + atezolizumab regimens (HR range: 0.56-0.62). Additionally, pembrolizumab + pemetrexed + platinum numerically improved OS over atezolizumab + paclitaxel + carboplatin + bevacizumab (HR: 0.65; 95% credible interval: 0.43, 1.01). Pembrolizumab + pemetrexed + platinum had 95.6% probability of being the best treatment regimen for OS.
CONCLUSION
Pembrolizumab + pemetrexed + platinum is likely the most efficacious first-line regimen for metastatic NSq-NSCLC.
Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Carboplatin; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Humans; Lung Neoplasms; Neoplasm Metastasis; Paclitaxel; Pemetrexed; Survival Rate
PubMed: 30712477
DOI: 10.2217/imt-2018-0193 -
Clinical Oral Investigations Apr 2019This study aims to perform a systematic review and meta-analysis of clinical trials in order to evaluate the clinical and radiographic success rates of primary teeth... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This study aims to perform a systematic review and meta-analysis of clinical trials in order to evaluate the clinical and radiographic success rates of primary teeth pulpotomy performed with biodentine, when compared to MTA.
METHODS
Search strategies were conducted in nine databases on August 5th, 2017, update on February 14th, 2018. Clinical articles were selected, which were in accordance with the inclusion and exclusion criteria and the research objective. They were analyzed by meta-analysis at three time points (6, 12, and 18 months).
RESULTS
Out of the 233 publications initially identified, only 9 studies that fulfilled the inclusion criteria were included in the review. The 6-month overall clinical (RR = 0.99; 95% CI = 0.96-1.02, p = 0.92) and radiographic success rates (RR = 0.96; 95% CI = 0.92-1.00, p = 0.28) showed that biodentine vs. MTA did not differ statistically. The 12 and 18-month overall clinical success rates, respectively (RR = 1.01; 95% CI = 0.97-1.04, p = 0.77; RR = 0.98; 95% CI = 0.92-1.05, p = 0.74) and radiographic success rates, respectively (RR = 0.97; 95% CI = 0.92-1.02, p = 0.11; RR = 1.00; 95% CI = 0.91-1.10, p = 0.56) also showed that biodentine vs. MTA did not differ statistically.
CONCLUSION
There is no superiority of one material over the other, MTA versus biodentine.
CLINICAL RELEVANCE
This systematic review comparing the performance of biodentine in relation to the MTA when used in the pulpotomy technique in primary teeth. Although MTA is considered the gold standard material for pulpotomy procedures, it has some drawbacks (poor handling, staining potential, long setting time); thus, it is important to evaluate the clinical performance of other calcium silicate-based cements like biodentine that overcome this drawbacks.
Topics: Calcium Compounds; Child; Child, Preschool; Drug Combinations; Humans; Pemetrexed; Pulpotomy; Silicates; Tooth, Deciduous
PubMed: 30238414
DOI: 10.1007/s00784-018-2616-6 -
Respiratory Medicine Aug 2018Advanced malignant pleural mesothelioma (MPM) is generally treated with platinum/pemetrexed-based first-line therapy. Once the disease progresses, evidence for the... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Advanced malignant pleural mesothelioma (MPM) is generally treated with platinum/pemetrexed-based first-line therapy. Once the disease progresses, evidence for the efficacy of palliative treatments is lacking, and platinum re-challenge or single-agent chemotherapy are commonly used. To assess the effects of cytostatic or targeted therapy for treating MPM, we performed a systematic review and meta-analysis.
MATERIAL AND METHODS
PubMed, the Cochrane Library, and Embase databases were searched to identify published articles on second-line treatments for recurrent or advanced mesothelioma. Inclusion criteria were publication in the English language, describing clinical trials with 20 or more patients, and evaluability for efficacy and for receiving second-line systemic therapies. Data were pooled using number of events/number of evaluable patients, median overall survival (OS) and progression-free survival (PFS), according to a fixed or random effect model. Pooled median OS was the primary endpoint.
RESULTS
A total of 49 eligible studies (n = 3938 patients; range, 12-400) were identified. Median progression-free survival (PFS) was 3.4 months (95%CI 2.87-3.93). Median pooled OS was 7.86 (95%CI 7.01-8.72). The pooled overall response rate (ORR) was 8.63% (95%CI 6-11.26), and the pooled disease control rate (DCR) was 54.8% (95%CI 48.9-60.6). Median pooled OS with platinum- and pemetrexed-based chemotherapy were 7.93 and 7.78 months, respectively.
CONCLUSIONS
There remains uncertainty about the ideal second-line agent for MPM. Based on this meta-analysis, palliative chemotherapy or other experimental agents can be considered for patients with MPM who desire further treatment after their disease has progressed, during or after first-line therapy.
Topics: Antineoplastic Agents; Clinical Trials as Topic; Female; Humans; Lung Neoplasms; Male; Mesothelioma; Mesothelioma, Malignant; Pemetrexed; Platinum; Progression-Free Survival; Treatment Outcome
PubMed: 30053976
DOI: 10.1016/j.rmed.2018.06.026 -
BioMed Research International 2018To evaluate the effect of combination maintenance therapy of pemetrexed plus bevacizumab for patients with advanced non-small cell lung cancer. (Meta-Analysis)
Meta-Analysis
PURPOSE
To evaluate the effect of combination maintenance therapy of pemetrexed plus bevacizumab for patients with advanced non-small cell lung cancer.
METHODS
We identified relevant studies by electronic search (Embase, PubMed, Cochrane, and Web of Science from 1 January 1960 to 29 October 2016) and manual search. The primary outcome of interest was progression-free survival (PFS) and secondary end point included overall survival (OS) and toxicities. The data was pooled for quantitative analysis and the final effect size was reported as hazard ratio (HR) for survival outcomes and relative risk (RR) for safety outcomes, both with a random-effects model.
RESULTS
Three randomized controlled trials enrolling 1302 patients with advanced non-small cell lung cancer were included in this meta-analysis. An evident PFS improvement (HR = 0.73, 95% CI = 0.63-0.83, < 0.01) was observed in patients with pemetrexed and bevacizumab combination maintenance therapy compared with single-agent maintenance therapy, yet it did not subsequently lead to a significant improvement in OS (HR = 0.97, 95% CI = 0.84-1.10, = 0.66). Our analysis also showed statistically increased risks for provoking grade 3-4 adverse events in patients managed using pemetrexed plus bevacizumab combination (RR = 1.59, 95% CI = 1.07-2.36, = 0.022).
CONCLUSIONS
Pemetrexed plus bevacizumab combination maintenance therapy leads to significant improvement in PFS but not in OS for patients with advanced non-small cell lung cancer, which also increases the risks of grade 3-4 adverse events. Yet, in view of the limitation of existing studies and this meta-analysis, current evidence is not adequate to support routine use of pemetrexed-bevacizumab maintenance.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Pemetrexed; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 29998136
DOI: 10.1155/2018/5839081 -
OncoTargets and Therapy 2018The development of acquired resistance to the first-line epidermal growth factor-tyrosine kinase inhibitor (EGFR-TKI) treatment in non-small-cell lung cancer (NSCLC) is...
Chemotherapy with or without pemetrexed as second-line regimens for advanced non-small-cell lung cancer patients who have progressed after first-line EGFR TKIs: a systematic review and meta-analysis.
PURPOSE
The development of acquired resistance to the first-line epidermal growth factor-tyrosine kinase inhibitor (EGFR-TKI) treatment in non-small-cell lung cancer (NSCLC) is inevitable, and most of these patients needed second-line chemotherapy. Furthermore, the optimum chemotherapeutic regimen is unclear. The aim of this meta-analysis was to evaluate the chemotherapeutic regimens "with-pemetrexed" versus "non-pemetrexed" in advanced NSCLC patients who had progressed after first-line EGFR-TKIs.
MATERIALS AND METHODS
We searched PubMed, Embase, Cochrane Library, and the Web of science for relevant clinical trials. Outcomes analyzed were response rate (RR), disease control rate (DCR), 1-year survival rate (1-year SR), progression-free survival (PFS), and overall survival (OS).
RESULTS
One randomized controlled trial (RCT) and three retrospective studies were included in this meta-analysis, covering a total of 354 patients. The results showed that there was no significant difference between with-pemetrexed arm and non-pemetrexed arm in RR (OR 1.43, 95% CI 0.85-2.41, =0.18), DCR (OR 1.5, 95% CI 0.94-2.39, =0.09), and 1-year SR (OR 1.47, 95% CI 0.79-2.74, =0.22). But the with-pemetrexed chemotherapeutic regimens significantly improved the PFS (HR 0.61, 95% CI 0.46-0.81, =0.0005) and OS (HR 0.62, 95% CI 0.42-0.90, =0.01).
CONCLUSION
The second-line with-pemetrexed chemotherapeutic regimens provided significantly longer PFS and OS than non-pemetrexed chemotherapeutic regimens. These findings indicate that the with-pemetrexed chemotherapeutic regimen may be an optimal second-line chemotherapeutic regimen for patients with advanced NSCLC following EGFR-TKI failure.
PubMed: 29983578
DOI: 10.2147/OTT.S160147