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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 -
Thorax Jan 2002Lung cancer remains a devastating disease with few effective treatment options. Recent developments in chemotherapy have led to cautious optimism. This paper reviews the... (Review)
Review
BACKGROUND
Lung cancer remains a devastating disease with few effective treatment options. Recent developments in chemotherapy have led to cautious optimism. This paper reviews the evidence on the clinical and cost effectiveness of four of the new generation drugs for patients with lung cancer.
METHODS
A systematic review of randomised controlled trials (RCTs) identified from 11 electronic databases (including Medline, Cochrane library and Embase), reference lists and contact with experts and industry was performed to assess clinical effectiveness of paclitaxel, docetaxel, gemcitabine and vinorelbine. Clinical effectiveness was assessed using the outcomes of patient survival, quality of life, and adverse effects. Cost effectiveness was assessed by development of a costing model and presented as incremental cost per life year saved (LYS) compared with best supportive care (BSC).
RESULTS
Of the 33 RCTs included, five were judged to be of good quality, 10 of adequate quality, and 18 of poor quality. Gemcitabine, paclitaxel, and vinorelbine as first line treatment and docetaxel as second line treatment appear to be more beneficial for non-small cell lung cancer than BSC and older chemotherapy agents, increasing patient survival by 2-4 months against BSC and some comparator regimes. These gains in survival do not appear to be at the expense of quality of life. Survival gains were delivered at reasonable levels of incremental cost effectiveness for vinorelbine, vinorelbine with cisplatin, gemcitabine, gemcitabine with cisplatin, and paclitaxel with cisplatin regimens compared with BSC.
CONCLUSION
Although the clinical benefits of the new drugs appear relatively small, their benefit to patients with lung cancer appears to be worthwhile and cost effective.
Topics: Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cost of Illness; Cost-Benefit Analysis; Deoxycytidine; Docetaxel; Humans; Lung Neoplasms; Paclitaxel; Quality of Life; Randomized Controlled Trials as Topic; Sensitivity and Specificity; Taxoids; Treatment Outcome; Vinblastine; Vinorelbine; Gemcitabine
PubMed: 11809985
DOI: 10.1136/thorax.57.1.20 -
Health Technology Assessment... 2000SECOND-LINE TREATMENT, PACLITAXEL (MEDIAN PROGRESSION-FREE SURVIVAL): The median progression-free survival in the paclitaxel arm was 3.5 months. This was significantly... (Review)
Review
SECOND-LINE TREATMENT, PACLITAXEL (MEDIAN PROGRESSION-FREE SURVIVAL): The median progression-free survival in the paclitaxel arm was 3.5 months. This was significantly longer than the mitomycin control arm (1.6 months, p = 0.026). BREAST CANCER - SECOND-LINE TREATMENT, PACLITAXEL (MEDIAN OVERALL SURVIVAL): The median length of overall survival in the paclitaxel arm was 12.7 months, compared with 8.4 months in the mitomycin arm. BREAST CANCER - SECOND-LINE TREATMENT, PACLITAXEL (QUALITY OF LIFE): Quality of life was not reported. BREAST CANCER - SECOND-LINE TREATMENT, PACLITAXEL (ECONOMIC EVALUATION): The only economic evaluation that compared paclitaxel with control (mitomycin) was submitted in confidence and has been removed from this report. Six economic evaluations involved comparisons of paclitaxel and docetaxel, which are given below. BREAST CANCER - SECOND-LINE TREATMENT, DOCETAXEL: Four randomised controlled Phase III trials were identified: 303 Study, 304 Study, Scand and Bonneterre. A total of 1092 patients were included. One of these was a preliminary report of a study before completion of accrual (Bonneterre). Patients in the 303 Study had previously received chemotherapy involving alkylating agents; those in the other three had received anthracyclines. There were six economic evaluations on docetaxel. BREAST CANCER - SECOND-LINE TREATMENT, DOCETAXEL (QUALITY OF TRIALS): The 303 and 304 Studies were analysed on an intention to treat basis; the Scand trial excluded a single patient. The length of follow-up ranged from 11 months (Scand) to 23 months (303 Study). At least two-thirds of the participants in these trials had died. The Scand study recommended cross-over to alternate treatment on objective signs of disease progression. Patients crossing over in this way were violating the randomisation; however, no details were given concerning whether or not such patients were censored. In the economic analyses, there were no direct comparisons for the estimation of benefits. BREAST CANCER - SECOND-LINE TREATMENT, DOCETAXEL (MEDIAN PROGRESSION-FREE SURVIVAL): The median progression-free survival in the docetaxel arm ranged from 4.75 months (304 Study) to 7 months (Bonneterre). Patients in the docetaxel arms of the 304 and Scand studies had significantly longer progression-free survivals than controls (4.75 months versus 2.75 months, p = 0.001; 6.3 months versus 3 months, p = 0.001). BREAST CANCER - SECOND-LINE TREATMENT, DOCETAXEL (MEDIAN OVERALL SURVIVAL): The median overall survival in the docetaxel arm ranged from 10.4 months (Scand) to 15 months (303 Study). Patients in the docetaxel arms of the 304 Study survived for significantly longer than the mitomycin plus vinblastine arm (11.4 months versus 8.7 months, p = 0.03). BREAST CANCER - SECOND-LINE TREATMENT, DOCETAXEL (QUALITY OF LIFE): Quality of life was evaluated in two of the trials: the 303 and 304 Studies. There were no significant differences between docetaxel and control in either of these trials in terms of global health status, although differences were apparent on some subscales. These did not appear to follow a consistent pattern across the trials. BREAST CANCER - SECOND-LINE TREATMENT, DOCETAXEL (ECONOMIC EVALUATIONS): All six of these involved comparisons of paclitaxel and docetaxel, where the range of cost-utility ratios for incremental quality-adjusted life-years (QALYs) gained was pound 1990-pound 2431. In addition, three analyses compared docetaxel and vinorelbine. The cost-utility ratio for incremental QALYs gained was pound 14,050 in the only one of these carried out in the UK. OVARIAN CANCER - FIRST-LINE TREATMENT, PACLITAXEL: Four randomised controlled Phase III trials were identified: EORTC, TITGANZ, E1193 and CA139-278. (ABSTRACT TRUNCATED)
Topics: Antineoplastic Agents, Phytogenic; Breast Neoplasms; Cost-Benefit Analysis; Disease-Free Survival; Docetaxel; Female; Humans; Ovarian Neoplasms; Paclitaxel; Quality of Life; Survival Analysis; Taxoids
PubMed: 11074389
DOI: No ID Found -
Health Technology Assessment... 2001The incidence of lung cancer is declining following a drop in smoking rates, but it is still the leading cause of death from cancer in England and Wales, with about... (Review)
Review
BACKGROUND
The incidence of lung cancer is declining following a drop in smoking rates, but it is still the leading cause of death from cancer in England and Wales, with about 30,000 deaths a year. Survival rates for lung cancer are poor everywhere, but they appear to be better in the rest of the European Community and the USA than in the UK. Only about 5 per cent of people with lung cancer survive for 5 years, and nearly all of these are cured by surgery after fortuitously early diagnosis. At present, only a small proportion of patients (probably about 5 per cent) with non-small-cell lung cancer are being given chemotherapy. Some centres treat a greater proportion.
OBJECTIVES
This review examines the clinical effectiveness and cost-effectiveness of four of the newer drugs - vinorelbine, gemcitabine, paclitaxel and docetaxel - used for treating the most common type of lung cancer (non-small-cell lung cancer). The first three drugs are used for first-line treatment, but at present docetaxel is used only after first-line chemotherapy has failed.
METHODS
This report was based on a systematic literature review and economic modelling, supplemented by cost data. RESULTS - NUMBER AND QUALITY OF STUDIES: A reasonable number of randomised trials were found - three for docetaxel, six for gemcitabine, five for paclitaxel and 13 for vinorelbine. The quality of the trials was variable but good overall. There was a wide range of comparators. Some trials compared chemotherapy with best supportive care (BSC), which involves care that aims to control symptoms, with palliative radiotherapy if needed, but not to prolong life. Others compared the newer drugs against previous drugs or combinations. RESULTS - SUMMARY OF BENEFITS: The gains in duration of survival with the new drugs are modest - a few months - but worthwhile in a condition for which the untreated survival is only about 5 months. There are also gains in quality of life compared with BSC, because on balance the side-effects of some forms of chemotherapy have less effect on quality of life than the effects of uncontrolled spread of cancer. RESULTS - COSTS: The total cost to the NHS of using these new drugs in England and Wales might be about GBP 10 million per annum, but is subject to a number of factors. There would be non-financial constraints on any increase in chemotherapy for the next few years, such as staffing; the number of patients choosing to have the newer forms of chemotherapy is not yet known; and the costs of the drugs may fall, for example, as generic forms appear. RESULTS - COST PER LIFE-YEAR GAINED: The available data did not provide an entirely satisfactory basis for cost-effectiveness calculations. The main problem was the lack of direct comparisons of the new drugs. In order to strengthen the analysis, three different modelling approaches were used: pairwise comparisons using trial data; cost-minimisation analysis, as if all the new regimens were of equal efficacy; and cost-effectiveness analysis pooling the results of several trials with different comparators, giving indirect comparisons of the new drugs by using BSC as the common comparator. A number of different scenarios were explored through extensive sensitivity analysis in each model. Outcomes were expressed in incremental cost per life-year saved or incremental cost, versus BSC. There was insufficient evidence from which to derive cost per quality-adjusted life-year. In first-line treatment, vinorelbine, gemcitabine, and the lower-dose paclitaxel plus cisplatin combinations generally performed well against BSC under a range of different scenarios and especially when given as a maximum of 3 cycles. Incremental cost per life-year gained (LYG) versus BSC varied depending on scenario, but baseline figures based on trial data and protocols were: single-agent vinorelbine, pound 2194 per LYG; vinorelbine plus cisplatin, pound 5206; single-agent gemcitabine, pound 5690; gemcitabine plus cisplatin, pound 10,041; and paclitaxel plus cisplatin, pound 8537. In second-line chemotherapy, docetaxel gave a cost per LYG of pound 17,546, again well within the range usually accepted as cost-effective. However, in routine care, the impact of therapy would be regularly reviewed, and continuation would depend on response, side-effects, patient choice and clinical judgement. Chemotherapy would be stopped in non-responders, making chemotherapy more cost-effective. A 'real-life' scenario in which 60 per cent of patients receive only 1 or 2 cycles of chemotherapy gives much lower costs per LYG, with single-agent gemcitabine, single-agent vinorelbine, and paclitaxel plus platinum appearing to be cost-saving compared with BSC; the incremental cost of gemcitabine plus cisplatin would be pound 2478 per LYG, and of vinorelbine plus cisplatin, pound 2808. At the very least, gains in duration of survival were achieved without diminution of quality of life (at best, they improved quality) and with relatively low incremental cost. Comparisons among the individual drugs should be viewed with caution because they have had to be based on indirect comparisons. RESULTS - LIMITATIONS OF THE ANALYSIS: Each of the three models had limitations. The cost-effectiveness estimates from the pairwise comparisons were based on single studies. The cost-minimisation analysis assumed that the regimens have equal efficacy in practice. The cost-effectiveness analysis had to be based on pooling data from individual trials. The costs of BSC, inpatient stay and outpatient visits were from Scottish data. Median rather than mean data on duration of survival have been used in the analysis, because most of the trials reported only median data. Median survival and number of drug cycles were calculated by averaging across a number of studies, rather than being reliant on one particular study. The costs of the less expensive antiemetics cited in the trials were omitted. The use of more modern and costly antiemetics would have a modest detrimental effect on cost-effectiveness. In the absence of published data, an estimate was made of the cost of side-effects of chemotherapy, in particular hospital admissions, and applied to all the new regimens. In practice, admissions related to side-effects and their respective costs are likely to vary by regimen.
CONCLUSIONS
The new drugs for non-small-cell lung cancer extend life by only a few months compared with BSC, but appear to do so without net loss in quality of life and at a cost per LYG that is much lower than for many other NHS activities. Depending on assumptions used, these new drugs range from being cost-effective, as conventionally accepted, to being cost-saving. CONCLUSIONS - IMPLICATIONS OF THE NEWER DRUGS: One of the present constraints on chemotherapy is availability of inpatient beds. The advent of newer and gentler forms of chemotherapy given on an outpatient basis would not only overcome this, but it would allow more patients to be treated. This might apply particularly to older patients. The treatment of more patients would increase workload for oncologists, cancer nurses and pharmacists. The Government has already announced increased expenditure on staff for cancer care. The previously pessimistic attitudes to chemotherapy in non-small-cell lung cancer are changing in the wake of the newer agents, and this shift is likely to increase referral. CONCLUSIONS - NEED FOR FURTHER RESEARCH: Recent advances in chemotherapy are welcome, but their effects remain small for patients with non-small-cell lung cancer. Much more research is needed into better drugs, better combinations, new ways of assessing the likelihood of response and especially direct comparisons between the new regimens. This research would be aided by having a greater proportion of patients involved in trials, but there will be infrastructure implications of increased participation.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cost-Benefit Analysis; Deoxycytidine; Docetaxel; England; Humans; Lung Neoplasms; Paclitaxel; Quality of Life; Survival Rate; Taxoids; Vinblastine; Vinorelbine; Wales; Gemcitabine
PubMed: 12065068
DOI: 10.3310/hta5320 -
Health Technology Assessment... Feb 2004To examine the clinical effectiveness and cost-effectiveness of oral capecitabine for locally advanced and metastatic breast cancer in relation to its licensed... (Comparative Study)
Comparative Study Review
OBJECTIVE
To examine the clinical effectiveness and cost-effectiveness of oral capecitabine for locally advanced and metastatic breast cancer in relation to its licensed indications.
DATA SOURCES
Twenty-three electronic databases and other databases of ongoing research and Internet resources, bibliographies of retrieved articles and industry submissions.
REVIEW METHODS
Two reviewers independently screened and assessed all titles and/or abstracts including economic evaluations. Randomised controlled trials (RCTs) and observational studies that investigated capecitabine monotherapy, in patients pretreated with an anthracycline-containing regimen or a taxane, or capecitabine in combination with docetaxel, in patients pretreated with an anthracycline-containing regimen, were included. The economic evaluation was based on data reported in the manufacturer's submission.
RESULTS
For capecitabine monotherapy, 12 uncontrolled observational studies were identified. The methodological quality of the studies was low. Capecitabine demonstrated antitumour activity, but was associated with a particular risk of hand-foot syndrome and diarrhoea. Economic evaluation was hampered by the poor quality of the published studies, but compared indirectly with vinorelbine, capecitabine was associated with lower costs and improved patient outcomes. For capecitabine in combination with docetaxel, one RCT was identified. Combination therapy was superior to single-agent docetaxel in terms of survival, time to disease progression and overall response. Adverse events occurred more frequently with combination therapy. The economic evaluation demonstrated an overall improved QALY score for combination therapy with a slight reduction in costs.
CONCLUSIONS
No conclusions could be drawn regarding the therapeutic benefit of capecitabine monotherapy; RCTs are required. Capecitabine appeared cost-effective compared with vinorelbine, but serious doubts remain; the poor quality of the trials may invalidate this conclusion. Based on limited evidence, combination therapy was more effective than single-agent docetaxel and likely to be cost-effective, but was associated with higher incidences of hand-foot syndrome, nausea, diarrhoea and stomatitis.
Topics: Administration, Oral; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Capecitabine; Cost-Benefit Analysis; Deoxycytidine; Disease Progression; Docetaxel; Drug Therapy, Combination; Female; Fluorouracil; Humans; Neoplasm Metastasis; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; State Medicine; Survival Rate; Taxoids; Treatment Outcome; United Kingdom
PubMed: 14960257
DOI: 10.3310/hta8050 -
Health Technology Assessment... May 2007To assess the clinical effectiveness and cost-effectiveness of gemcitabine, used in combination with paclitaxel, as a second-line treatment for people with metastatic... (Review)
Review
OBJECTIVES
To assess the clinical effectiveness and cost-effectiveness of gemcitabine, used in combination with paclitaxel, as a second-line treatment for people with metastatic breast cancer who have relapsed following treatment with anthracycline-based chemotherapy.
DATA SOURCES
Electronic databases were searched from inception to March 2006. Clinical advisers were also consulted.
REVIEW METHODS
A systematic review of the literature was undertaken to appraise the clinical and cost-effectiveness of gemcitabine. A Markov state transition model was developed for the economic evaluation.
RESULTS
The systematic review identified only one randomised controlled trials (RCT), and this has not yet been fully published. The methodological quality and quality of reporting of the included trial were assessed to be poor using standard criteria, but this may be due to the lack of information in the limited publications rather than being a fair reflection of the trial's quality. This RCT compared gemcitabine and paclitaxel therapy with paclitaxel monotherapy in 529 patients with metastatic breast cancer who had previously received anthracyclines, but no prior chemotherapy for metastatic breast cancer. Approximately 71% of the gemcitabine/paclitaxel patients survived for 1 year, compared with 61% of the paclitaxel group. The hazard ratio showed a 26% lower chance of survival in the paclitaxel group, and time to progressive disease was also shorter in this group. The overall response rate was higher in the gemcitabine/paclitaxel group than in the paclitaxel group. Adverse events, particularly neutropenia, were more common with gemcitabine/paclitaxel combination therapy than with paclitaxel therapy alone. The economic model was run for a simulation of 1000 patients, assuming that chemotherapy continued until patients' disease progressed. This base-case analysis found an incremental cost-effectiveness ratio (ICER) of 58,876 pounds per quality-adjusted life-year (QALY) gained and 30,117 pounds per life-year gained. The model was re-run with treatment restricted to a maximum of six cycles per patient, reflecting normal practice. This yielded an ICER of 38,699 pounds per QALY gained and 20,021 pounds per life-year gained.
CONCLUSIONS
The review of clinical effectiveness is based on data from a single RCT that has not yet been fully published. While only tentative conclusions can be drawn from this, the evidence may indicate that treatment with gemcitabine and paclitaxel confers an improved outcome for patients in terms of survival and disease progression, but at the cost of increased toxicity. An economic model developed for this review reflects high costs per QALY for this treatment combination. The base-case analysis shows high ICERs, with costs per QALY gained close to 60,000 pounds. Adopting a more realistic treatment protocol, with chemotherapy limited to a maximum of six cycles, gives a more favourable cost-effectiveness estimate. However, this was still higher than would usually be considered to be a cost-effective treatment from the NHS's perspective. Future research recommendations include an update of this review in 12-18 months' time, by which time the included RCT should be fully published. It would also be useful to compare gemcitabine with currently used treatments for metastatic breast cancer, including capecitabine and vinorelbine.
Topics: Age Factors; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cost-Benefit Analysis; Deoxycytidine; Female; Humans; Markov Chains; Models, Economic; Neoplasm Metastasis; Neoplasm Recurrence, Local; Paclitaxel; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Risk Factors; Gemcitabine
PubMed: 17462169
DOI: 10.3310/hta11190 -
Molecular and Clinical Oncology Sep 2015The present study aimed to compare the effects of vinorelbine-based neoadjuvant chemotherapy and vinorelbine-free regimens. A meta-analysis of all the relevant...
The present study aimed to compare the effects of vinorelbine-based neoadjuvant chemotherapy and vinorelbine-free regimens. A meta-analysis of all the relevant randomized controlled trials was performed to investigate the improvement in pathological complete response (pCR), overall response rate (ORR) and breast-conserving surgery (BCS). The PubMed and Embase databases were searched for relevant studies reporting randomized controlled trials comparing vinorelbine-based neoadjuvant chemotherapy with vinorelbine-free regimens until July 2013. Risk ratios/odds ratio and 95% confidence intervals (CIs) were used to estimate the association between vinorelbine in neoadjuvant chemotherapy and various efficacy outcomes. Fixed- or random-effect models were adopted to pool the data. Five eligible studies with a total of 1,495 patients were included in the meta-analysis. Compared to vinorelbine-free chemotherapy, vinorelbine-based regimens demonstrated no significant improvement in clinical outcomes including: pCR [relative risk (RR)=1.016; 95% CI, 0.738-1.399; P=0.922], ORR (RR=1.048; 95% CI, 0.969-1.133; P=0.239) and BCS (RR=1.764; 95% CI, 0.734-4.239; P=0.205). However, vinorelbine-based regimens were associated with a lower incidence of grade 3-4 alopecia (OR, 0.617; 95% CI, 0.448-0.848; P=0.003). In a hierarchical analysis for patients who received neoadjuvant chemotherapy, the proportion of subjects achieving pCR was significantly increased when HER2-amplified (RR=2.31; 95% CI, 1.20-4.43; P=0.01) and hormone receptor negative (RR=0.488; 95% CI, 0.263-0.908; P=0.023). The present review confirms that neoadjuvant chemotherapy vinorelbine-based regimens are unlikely to emerge as superior to pCR, ORR and BCS. Hierarchical analysis indicated that the HER2-amplified and hormone receptor-negative patients were significantly associated with a pathological response rate.
PubMed: 26623067
DOI: 10.3892/mco.2015.576 -
Health Technology Assessment... Jul 2013The National Institute for Health and Care Excellence (NICE) has issued multiple guidance for the first-line management of patients with lung cancer and recommends... (Review)
Review
Clinical effectiveness and cost-effectiveness of first-line chemotherapy for adult patients with locally advanced or metastatic non-small cell lung cancer: a systematic review and economic evaluation.
BACKGROUND
The National Institute for Health and Care Excellence (NICE) has issued multiple guidance for the first-line management of patients with lung cancer and recommends different combinations of chemotherapy treatments. This review provides a synthesis of clinical effectiveness and cost-effectiveness evidence supporting current guidance.
OBJECTIVES
To evaluate the clinical effectiveness and cost-effectiveness of first-line chemotherapy currently licensed in Europe and recommended by NICE, for adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC).
DATA SOURCES
Three electronic databases (MEDLINE, EMBASE and The Cochrane Library) were searched from 2001 to August 2010.
REVIEW METHODS
Trials that compared first-line chemotherapy currently licensed in Europe and recommended by NICE in chemotherapy-naive adult patients with locally advanced or metastatic NSCLC were included. Data on key outcomes including, but not limited to, overall survival (OS), progression-free survival (PFS) and adverse events (AEs) were extracted. For the assessment of cost-effectiveness, outcomes included incremental cost per quality-adjusted life-year (QALY) gained. Analyses were performed for three NSCLC subpopulations: patients with predominantly squamous disease, patients with predominantly non-squamous disease and patients with epidermal growth factor receptor (EGFR) mutation-positive (M+) status. Meta-analysis and mixed-treatment comparison methodology were conducted where appropriate.
RESULTS
Twenty-three trials involving > 11,000 patients in total met the inclusion criteria. The quality of the trials was poor. In the case of patients with squamous disease, there were no statistically significant differences in OS between treatment regimes. The mixed-treatment comparison demonstrated that, in patients with non-squamous disease, pemetrexed (Alimta®, Eli Lilly and Company; PEM) + platinum (PLAT) increases OS statistically significantly compared with gemcitabine (Gemzar®, Eli Lilly and Company; GEM) + PLAT [hazard ratio (HR) = 0.85; 95% confidence interval (CI) 0.74 to 0.98] and that paclitaxel (Abraxane®, Celgene Corporation; PAX) + PLAT increases OS statistically significantly compared with docetaxel (Taxotere®, Sanofi-aventis; DOC) + PLAT (HR = 0.79, 95% CI 0.66 to 0.93). None of the comparisons found any statistically significant differences in OS among patients with EGFR M+ status. Direct meta-analysis showed a statistically significant improvement in PFS with gefitinib (Iressa®, AstraZeneca; GEF) compared with DOC + PLAT and PAX + PLAT (HR = 0.49; 95% CI 0.33 to 0.73; and HR = 0.38; 95% CI 0.24 to 0.60, respectively). No papers related to UK decision-making were identified. A de novo economic model was developed. Using list prices (British National Formulary), cisplatin (CIS) doublets are preferable to carboplatin doublets, but this is reversed if electronic market information tool prices are used, in which case drug administration costs then become more important than drug acquisition costs. For patients with both squamous and non-squamous disease, moving from low to moderate willingness-to-pay thresholds, the preferred drugs are PAX → GEM → DOC. However, in patients with non-squamous disease, PEM + CIS resulted in increased OS and would be considered cost-effective up to £35,000 per QALY gained. For patients with EGFR M+, use of GEF compared with PAX or DOC yields very high incremental cost-effectiveness ratios. Vinorelbine (Navelbine®, Pierre Fabre Pharmaceutical Inc.) was not shown to be cost-effective in any comparison.
LIMITATIONS
Poor trial quality and a lack of evidence for all drug comparisons complicated and limited the data analysis. Outcomes and adverse effects are not consistently combined across the trials. Few trials reported quality-of-life data despite their relevance to patients and clinicians.
CONCLUSIONS
The results of this comprehensive review are unique to NSCLC and will assist clinicians to make decisions regarding the treatment of patients with advanced NSCLC. The design of future lung cancer trials needs to reflect the influence of factors such as histology, genetics and the new prognostic biomarkers that are currently being identified. In addition, trials will need to be adequately powered so as to be able to test for statistically significant clinical effectiveness differences within patient populations. New initiatives are in place to record detailed information on the precise chemotherapy (and targeted chemotherapy) regimens being used, together with data on age, cell type, stage of disease and performance status, allowing for very detailed observational audits of management and outcomes at a population level. It would be useful if these initiatives could be expanded to include the collection of health economics data.
FUNDING
The National Institute for Health Research Health Technology Assessment.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Clinical Trials as Topic; Cost-Benefit Analysis; ErbB Receptors; Humans; Lung Neoplasms; Neoplasm Metastasis; Quality-Adjusted Life Years
PubMed: 23886301
DOI: 10.3310/hta17310 -
Cureus Jan 2023Current non-small cell lung cancer (NSCLC) treatment consists of various combinations of surgery, chemotherapy, and/or radiation, depending on the tumor stage.... (Review)
Review
Current non-small cell lung cancer (NSCLC) treatment consists of various combinations of surgery, chemotherapy, and/or radiation, depending on the tumor stage. Individuals with stage II-IIIa NSCLC undergo surgery, followed by combination chemotherapy containing cisplatin, such as vinorelbine + cisplatin. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as gefitinib, act by inhibiting any signaling pathway containing the EGFR mutation and inhibiting the growth of NSCLC. TKI is a treatment option in advanced NSCLC, resulting in more prolonged progression-free survival (PFS). This manuscript aims to evaluate the influence of utilizing gefitinib - either alone or in combination with conventional chemotherapeutic drug regimens upon NSCLC patient profile survival parameters. A systematic literature review was conducted across multiple scientific literature repositories. The review was performed using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) 2020. There were six randomized clinical trials (RCT) and five retrospective studies. The overall consensus based on the end outcome of each published journal on the effectiveness of gefitinib as a treatment option for NSCLC indicated that there was a notable difference in overall survival (OS) and progression-free survival (PFS) and disease-free survival (DFS) datasets. Gefitinib use correlated with increased timeframes for multiple patient survival parameters within articles shortlisted in this investigation. However, more comprehensive investigations are required to validate such correlations. Gefitinib did demonstrate the potential to provide beneficial effects and counteract NSCLC within such patients.
PubMed: 36788891
DOI: 10.7759/cureus.33691 -
BMC Cancer May 2006Prostate cancer that has recurred after local therapy or disseminated distantly is usually treated with androgen deprivation therapy; however, most men will eventually... (Review)
Review
Non-hormonal systemic therapy in men with hormone-refractory prostate cancer and metastases: a systematic review from the Cancer Care Ontario Program in Evidence-based Care's Genitourinary Cancer Disease Site Group.
BACKGROUND
Prostate cancer that has recurred after local therapy or disseminated distantly is usually treated with androgen deprivation therapy; however, most men will eventually experience disease progression within 12 to 20 months. New data emerging from randomized controlled trials (RCTs) of chemotherapy provided the impetus for a systematic review addressing the following question: which non-hormonal systemic therapies are most beneficial for the treatment of men with hormone-refractory prostate cancer (HRPC) and clinical evidence of metastases?
METHODS
A systematic review was performed to identify RCTs or meta-analyses examining first-line non-hormonal systemic (cytotoxic and non-cytotoxic) therapy in patients with HRPC and metastases that reported at least one of the following endpoints: overall survival, disease control, palliative response, quality of life, and toxicity. Excluded were RCTs of second-line hormonal therapies, bisphosphonates or radiopharmaceuticals, or randomized fewer than 50 patients per trial arm. MEDLINE, EMBASE, the Cochrane Library, and the conference proceedings of the American Society of Clinical Oncology were searched for relevant trials. Citations were screened for eligibility by four reviewers and discrepancies were handled by consensus.
RESULTS
Of the 80 RCTs identified, 27 met the eligibility criteria. Two recent, large trials reported improved overall survival with docetaxel-based chemotherapy compared to mitoxantrone-prednisone. Improved progression-free survival and rates of palliative and objective response were also observed. Compared with mitoxantrone, docetaxel treatment was associated with more frequent mild toxicities, similar rates of serious toxicities, and better quality of life. More frequent serious toxicities were observed when docetaxel was combined with estramustine. Three trials reported improved time-to-disease progression, palliative response, and/or quality of life with mitoxatrone plus corticosteroid compared with corticosteroid alone. Single trials reported improved disease control with estramustine-vinblastine, vinorelbine-hydrocortisone, and suramin-hydrocortisone compared to controls. Trials of non-cytotoxic agents have reported equivocal results.
CONCLUSION
Docetaxel-based chemotherapy modestly improves survival and provides palliation for men with HRPC and metastases. Other than androgen deprivation therapy, this is the only other therapy to have demonstrated improved overall survival in prostate cancer in RCTs. Further investigations to identify more effective therapies for HRPC including the use of systemic therapies earlier in the natural history of prostate cancer are warranted.
Topics: Antineoplastic Agents; Drug Resistance, Neoplasm; Evidence-Based Medicine; Hormones; Humans; Male; Microtubules; Neoplasm Metastasis; Ontario; Prostatic Neoplasms
PubMed: 16670021
DOI: 10.1186/1471-2407-6-112