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European Journal of Cancer (Oxford,... Nov 2015Recent trials have suggested that maintenance treatments improve outcomes for patients not progressing after first-line therapy for advanced non-small-cell lung cancer... (Meta-Analysis)
Meta-Analysis Review
Bayesian network meta-comparison of maintenance treatments for stage IIIb/IV non-small-cell lung cancer (NSCLC) patients with good performance status not progressing after first-line induction chemotherapy: results by performance status, EGFR mutation, histology and response to previous induction.
BACKGROUND
Recent trials have suggested that maintenance treatments improve outcomes for patients not progressing after first-line therapy for advanced non-small-cell lung cancer (NSCLC). However, physicians have little guidance on selecting which patients benefit the most and what drug or regimen is optimal. Here, we report a systematic review and network meta-analysis of maintenance treatments in subgroups determined by performance status (PS), epidermal growth factor receptor (EGFR) mutation, histology and response to induction.
METHODS
PubMed and conference proceedings were reviewed and individual study relative efficacy measures were meta-analysed in a Bayesian hierarchical model. The primary outcome, overall survival (OS), was evaluated in terms of (i) posterior surface under cumulative ranking curve (SUCRA), (ii) probability of being best treatment, (iii) probability of outperforming no maintenance, and (iv) posterior median hazard ratio (95% credible interval). Secondary outcomes were progression-free survival (PFS) and adverse events.
FINDINGS
Twelve trials evaluating eight maintenance treatments in 3850 patients were meta-analysed. Selected maintenance treatments showed clinically meaningful benefits of ⩾20% reduction in hazards of death with ⩾90% probability of outperforming no maintenance in terms of OS: (i) switch to or continue pemetrexed (nonsquamous), continue gemcitabine, or switch to EGFR tyrosine kinase inhibitors (TKIs) for PS 0 patients, (ii) switch to pemetrexed (nonsquamous) for PS 1 patients, (iii) switch to EGFR TKI for EGFR mutation positive patients, (iv) switch to or continue pemetrexed or switch to EGFR TKI for nonsquamous patients, (v) continue gemcitabine for squamous patients, (vi) switch to docetaxel or continue gemcitabine for responders to induction, or (vii) switch to or continue pemetrexed (nonsquamous) or switch to EGFR TKI for patients with stable disease post-induction.
INTERPRETATION
Maintenance treatments show clinically meaningful survival benefits in good performance status patients with advanced NSCLC not progressing after first-line chemotherapy. Benefits are optimised by targeting specific maintenance to individual patients guided by PS, EGFR mutation status, histology and response to induction.
Topics: Antineoplastic Agents; Bayes Theorem; Carcinoma, Non-Small-Cell Lung; Deoxycytidine; Disease Progression; Disease-Free Survival; Docetaxel; Drug Substitution; ErbB Receptors; Genetic Predisposition to Disease; Humans; Induction Chemotherapy; Lung Neoplasms; Maintenance Chemotherapy; Markov Chains; Monte Carlo Method; Mutation; Neoplasm Staging; Pemetrexed; Phenotype; Protein Kinase Inhibitors; Risk Factors; Survival Analysis; Taxoids; Time Factors; Treatment Outcome; Gemcitabine
PubMed: 26364517
DOI: 10.1016/j.ejca.2015.07.007 -
Thorax Apr 2015Our aim was to evaluate the clinical effectiveness of chemotherapy treatments currently licensed in Europe and recommended by the National Institute for Health and Care... (Meta-Analysis)
Meta-Analysis Review
Our aim was to evaluate the clinical effectiveness of chemotherapy treatments currently licensed in Europe and recommended by the National Institute for Health and Care Excellence (NICE) for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). A systematic search of MEDLINE, EMBASE and the Cochrane Library for randomised controlled trials (RCTs) published from 2001 to 2010 was carried out. Relative treatment effects for overall survival (OS) and progression-free survival (PFS) were estimated using standard meta-analysis and mixed treatment comparison methodology. A total of 23 RCTs were included: 18 trials compared platinum-based chemotherapy, two compared pemetrexed and three compared gefitinib. There are no statistically significant differences in OS between any of the four third-generation chemotherapy regimens. There is statistically significant evidence that pemetrexed+platinum increases OS compared with gemcitabine+platinum. There are no statistically significant differences in OS between gefitinib and docetaxel+platinum or between gefitinib and paclitaxel+platinum. There is a statistically significant improvement in PFS with gefitinib compared with docetaxel+platinum and gefitinib compared with paclitaxel+platinum. Due to reduced generic pricing, third-generation chemotherapy regimens (except vinorelbine) are still competitive options for most patients. This research provides a comprehensive evidence base, which clinicians and decision-makers can use when deciding on the optimal first-line chemotherapy treatment regimen for patients diagnosed with locally advanced or metastatic NSCLC.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cost-Benefit Analysis; Drug Costs; Humans; Lung Neoplasms; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 25661113
DOI: 10.1136/thoraxjnl-2014-205914 -
Lung Cancer (Amsterdam, Netherlands) Mar 2015Current standard for locally advanced non-small cell lung cancer (NSCLC) is combined concurrent therapy with a platinum-based regimen. Preclinical synergistic activity... (Meta-Analysis)
Meta-Analysis Review
Concurrent pemetrexed and radiation therapy in the treatment of patients with inoperable stage III non-small cell lung cancer: a systematic review of completed and ongoing studies.
Current standard for locally advanced non-small cell lung cancer (NSCLC) is combined concurrent therapy with a platinum-based regimen. Preclinical synergistic activity of pemetrexed with radiation therapy (RT) and favorable toxicity profile has led to clinical trials evaluating pemetrexed in chemoradiation regimens. This literature search of concurrent pemetrexed and RT treatment of patients with stage III NSCLC included MEDLINE database, meeting abstracts, and the clinical trial registry database. Nineteen unique studies were represented across all databases including 11 phase I studies and eight phase II studies. Of the six phase II trials with mature data available, median overall survival ranged from 18.7 to 34 months. Esophagitis and pneumonitis occurred in 0-16% and 0-23% of patients, respectively. Of the ongoing trials, there is one phase III and four phase II trials with pemetrexed in locally advanced NSCLC. Pemetrexed can be administered safely at full systemic doses with either cisplatin or carboplatin concomitantly with radical doses of thoracic radiation therapy. While results from the ongoing phase III PROCLAIM trial are needed to address definitively the efficacy of pemetrexed-cisplatin plus RT in stage III NSCLC, available results from phase II trials suggest that this regimen has promising activity with an acceptable toxicity profile.
Topics: Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Combined Modality Therapy; Glutamates; Guanine; Humans; Lung Neoplasms; Neoplasm Staging; Pemetrexed; Radiotherapy; Treatment Outcome
PubMed: 25650301
DOI: 10.1016/j.lungcan.2014.12.003 -
ClinicoEconomics and Outcomes Research... 2015During these last years, there have been an increased number of new drugs for non-small cell lung cancer (NSCLC), with a growing financial effect on patients and... (Review)
Review
During these last years, there have been an increased number of new drugs for non-small cell lung cancer (NSCLC), with a growing financial effect on patients and society. The purpose of this article was to review the economics of first-line and maintenance NSCLC treatments. We reviewed economic analyses of NSCLC therapies published between 2004 and 2014. In first-line settings, in unselected patients with advanced NSCLC, the cisplatin gemcitabine doublet appears to be cost-saving compared with other platinum doublets. In patients with nonsquamous NSCLC, the incremental cost-effectiveness ratios (ICERs) per life-year gained (LYG) were $83,537, $178,613, and more than $300,000 for cisplatin-pemetrexed compared with, respectively, cisplatin-gemcitabine, cisplatin-carboplatin-paclitaxel, and carboplatin-paclitaxel-bevacizumab. For all primary chemotherapy agents, use of carboplatin is associated with slightly higher costs than cisplatin. In all the analysis, bevacizumab had an ICER greater than $150,000 per quality-adjusted life-year (QALY). In epidermal growth factor receptor mutated advanced NSCLC, compared with carboplatin-paclitaxel doublet, targeted therapy based on testing available tissue yielded an ICER of $110,644 per QALY, and the rebiopsy strategy yielded an ICER of $122,219 per QALY. Compared with the triplet carboplatin-paclitaxel-bevacizumab, testing and rebiopsy strategies had ICERs of $25,547 and $44,036 per QALY, respectively. In an indirect comparison, ICERs per LYG and QALY of erlotinib versus gefitinib were $39,431 and $62,419, respectively. In anaplastic lymphoma kinase-positive nonsquamous advanced NSCLC, the ICER of first-line crizotinib compared with that of chemotherapy was $255,970 per QALY. For maintenance therapy, gefitinib had an ICER of $19,214 per QALY, erlotinib had an ICER of $127,343 per LYG, and pemetrexed had an ICER varying between $183,589 and $205,597 per LYG. Most recent NSCLC strategies are based on apparently no cost-effective strategies if we consider an ICER below $50,000 per QALY an acceptable threshold. We need, probably on a countrywide level, to have a debate involving public health organizations and pharmaceutical companies, as well as clinicians and patients, to challenge the rising costs of managing lung cancer.
PubMed: 25548525
DOI: 10.2147/CEOR.S43328 -
Cancer Biomarkers : Section a of... 2015It remains controversial whether thymidylate synthase (TS) protein expression is associated with survival for patients with non-small cell lung cancer (NSCLC). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
It remains controversial whether thymidylate synthase (TS) protein expression is associated with survival for patients with non-small cell lung cancer (NSCLC).
OBJECTIVE
To evaluate prognostic and predictive significance of tumor TS protein level in NSCLC.
METHODS
Electronic searches were performed for relevant studies in PubMed, EMBASE, Web of Science, and Chinese Biomedical Literature Database. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were pooled for meta-analysis. Subgroup and sensitivity analyses were performed. Publication bias was evaluated by funnel plot and Begg's test.
RESULTS
Twenty-four studies, including 2280 patients, were eligible. This analysis showed that patients with low TS expression had statistically significantly longer OS and PFS than those with high TS (HR=0.51 and HR=0.49, respectively). Based on TS-targeted drug use status, TS expression was significantly associated with OS in pemetrexed (HR=0.42) and 5-Fluorouracil subgroups (HR=0.34), but not in no TS-targeted drug subgroup. There were similar results for PFS analyses. Sensitivity analysis indicated that the results were robust. Begg's test did not reveal any publication bias.
CONCLUSION
Low TS protein expression is a favorable predictive factor for better OS/PFS in NSCLC patients treated with TS-targeted drugs. Prognostic value of TS protein expression needs further validation.
Topics: Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Humans; Lung Neoplasms; Prognosis; Survival Analysis; Thymidylate Synthase
PubMed: 25524944
DOI: 10.3233/CBM-140432 -
Case Reports in Oncology May 2014To gain a better understanding of the role of pemetrexed in ovarian cancer patients, we conducted a systematic review of the published literature and evaluated a...
OBJECTIVE
To gain a better understanding of the role of pemetrexed in ovarian cancer patients, we conducted a systematic review of the published literature and evaluated a consecutive, single-institution series of non-study pemetrexed-treated patients.
METHODS/RESULTS
Thirteen published articles met this study's eligibility criteria, providing a total of 376 unique and evaluable ovarian cancer patients. This systematic review demonstrated tumor response rates with pemetrexed-based chemotherapy from 9 to 84%; the agent appeared to be well tolerated. Similarly, 13 consecutive patients with ovarian, fallopian tube, or primary peritoneal cancer were treated with pemetrexed at the Mayo Clinic, Rochester, Minn., USA, from 2004 through 2013. The median number of previous chemotherapy regimens was 4; most patients received single-agent pemetrexed (n = 9). Patients received a median of 2 cycles of pemetrexed-based chemotherapy; 1 patient received 10 cycles (7 months' worth) with treatment ongoing at the time of this report. The median survival from the start of pemetrexed was 4.8 months (95% confidence interval 1.2, 15 months). Two patients manifested a 50% drop in Ca-125 levels. Again, pemetrexed was relatively well tolerated.
CONCLUSION
Pemetrexed has antineoplastic activity in patients with ovarian cancer - even among those who have been heavily pretreated - and therefore merits further study.
PubMed: 25232324
DOI: 10.1159/000365885