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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 -
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 -
European Journal of Cancer (Oxford,... Nov 2009Currently available evidence does not provide definitive guidance regarding the optimal chemotherapy agents and combinations in anthracycline- and taxane-pretreated... (Review)
Review
INTRODUCTION
Currently available evidence does not provide definitive guidance regarding the optimal chemotherapy agents and combinations in anthracycline- and taxane-pretreated advanced breast cancer. We performed a systematic review of controlled clinical trials of the cytotoxic agents currently used for this population in Europe: capecitabine, gemcitabine, vinorelbine, docetaxel, paclitaxel and paclitaxel protein-bound particles.
METHOD
A systematic review of randomised (RCT) and non-randomised controlled clinical trials (non-RCTs). The primary outcomes of interest were overall survival (OS) and progression-free survival (PFS); secondary outcomes were duration of response (DR), overall response rate (ORR), adverse events and quality of life (QoL). Six electronic databases and grey literature sources were searched; reference tracking was performed on included publications. A narrative synthesis was conducted: heterogeneity of study design and interventions prevented meta-analysis.
RESULTS
No randomised controlled trial (RCT) found any significant differences between any of the regimens in terms of OS. In terms of PFS, only gemcitabine plus vinorelbine performed significantly better than its comparator, vinorelbine alone. For secondary outcomes, only capecitabine plus bevacizumab had a significantly better outcome than its comparator, capecitabine alone, in terms of ORR. A low quality non-RCT found that both capecitabine monotherapy and a combination of capecitabine plus vinorelbine were significantly more effective than vinorelbine alone in terms of OS and ORR. Across all trials, median OS for these patients typically remained less than 16 months.
CONCLUSION
The quantity and quality of the available evidence regarding the efficacy of the particular chemotherapy regimens in patients with advanced breast cancer pretreated with an anthracycline and a taxane is extremely limited. New effective therapies are sorely needed in this population.
Topics: Anthracyclines; Antineoplastic Agents; Breast Neoplasms; Clinical Trials as Topic; Disease-Free Survival; Female; Humans; Multicenter Studies as Topic; Neoplasm Metastasis; Taxoids; Treatment Outcome
PubMed: 19615886
DOI: 10.1016/j.ejca.2009.05.035 -
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 -
Zhongguo Fei Ai Za Zhi = Chinese... Feb 2010Cisplatin (DDP) plus vinorelbine (NVB) constitute the first-line regimen (NP regimen) for non-small cell lung cancer (NSCLC). Oxaliplatin (OXA) is another effective drug... (Review)
Review
BACKGROUND AND OBJECTIVE
Cisplatin (DDP) plus vinorelbine (NVB) constitute the first-line regimen (NP regimen) for non-small cell lung cancer (NSCLC). Oxaliplatin (OXA) is another effective drug in treatment of NSCLC with mild toxicities to gastrointestinal tract, kidney and bone marrow. The aim of this study is to evaluate the efficiency and safety between NVB plus OXA (NO) regimen and NP regimen for advanced NSCLC.
METHODS
We searched CBM CNKI, VIP, Cochrane Library, PubMed, EMBASE, ASCO etc. conference proceedings and internet information. Randomized controlled trials of NO versus NP for advanced NSCLC were included; we evaluated the quality of the included studies and analyzed data by Cochrane Collaboration's RevMan 5.0 software.
RESULTS
Fourteen randomized trials involving 1 270 patients were included. There were no statistical differences between NO and NP in overall response rate, disease control rate, 1-year survival rate, anemia and thrombocytopenia. Gastrointestinal toxicity, leucopenia, alopecia and kidney toxicity were more serious in NP (P < 0.05), but neuritis was more serious in NO, with significant difference (P < 0.05).
CONCLUSION
The clinical efficacy of NO and NP for advanced NSCLC was similar, but the side effects were different. The toxicity of NO has the tendency to be more tolerable.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Humans; Lung Neoplasms; Organoplatinum Compounds; Oxaliplatin; Randomized Controlled Trials as Topic; Treatment Outcome; Vinblastine; Vinorelbine
PubMed: 20673502
DOI: 10.3779/j.issn.1009-3419.2010.02.06 -
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 -
Acta Oncologica (Stockholm, Sweden) Sep 2020Overall prognosis of advanced sarcoma remains poor, optimization of systemic treatment is urgently needed in this setting. We systematically reviewed fully published...
Overall prognosis of advanced sarcoma remains poor, optimization of systemic treatment is urgently needed in this setting. We systematically reviewed fully published English-speaking literature about maintenance therapy and drug holiday in sarcoma patients management. We found that switch maintenance therapy with cyclophosphamide/vinorelbine improves the outcome of localized high-risk rhabdomyosarcoma. There is no other maintenance therapy recommended in sarcoma patients. After classical chemotherapy, maintenance therapy with immune-stimulating agents for localized osteosarcoma, bevacizumab for advanced angiosarcoma or pediatric advanced sarcoma, or mTOR inhibitors for metastatic sarcoma does not improve the outcome. Drug holiday has been assessed for metastatic gastrointestinal stromal tumor treated with imatinib as the first-line therapy or for metastatic soft-tissue sarcoma treated with trabectedin. Drug holiday has been found to lead to rapid disease progression and should be avoided. Data about both maintenance and drug holiday are spare in sarcoma management.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Cyclophosphamide; Disease-Free Survival; Drug Administration Schedule; Drug Substitution; Hemangiosarcoma; Humans; Maintenance Chemotherapy; Osteosarcoma; Prognosis; Rhabdomyosarcoma; Survival Rate; Trabectedin; Vinorelbine
PubMed: 32400254
DOI: 10.1080/0284186X.2020.1759825 -
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 -
Cytotherapy Feb 2019Cytokine-induced killer (CIK) cells are the most commonly used cellular immunotherapy for multiple tumors. To further confirm whether chemotherapy with CIK cells... (Meta-Analysis)
Meta-Analysis
Effectiveness and safety of chemotherapy with cytokine-induced killer cells in non-small cell lung cancer: A systematic review and meta-analysis of 32 randomized controlled trials.
BACKGROUND AIMS
Cytokine-induced killer (CIK) cells are the most commonly used cellular immunotherapy for multiple tumors. To further confirm whether chemotherapy with CIK cells improves clinical effectiveness and to reveal its optimal use in non-small cell lung cancer (NSCLC), we systematically reevaluated all relevant studies.
METHODS
We collected all studies about chemotherapy with CIK cells for NSCLC from the Medline, Embase, Web of Science, China National Knowledge Infrastructure Database (CNKI), Chinese Scientific Journals Full-Text Database (VIP), Wanfang Data, China Biological Medicine Database (CBM), Cochrane Central Register of Controlled Trials (CENTRAL), Chinese clinical trial registry (Chi-CTR), World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and U.S. clinical trials. We evaluated their quality according to the Cochrane evaluation handbook of randomized controlled trials (RCTs) (version 5.1.0), extracted the data using a standard data extraction form, synthesized the data using meta-analysis and finally rated the evidence quality using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
RESULTS
Thirty-two RCTs with 2250 patients were included, and most trials had unclear risk of bias. The merged risk ratios values and their 95% confidence intervals of meta-analysis for objective response rate, disease control rate, 1- and 2-year overall survival rates, 1- and 2-year progression-free survival rates were as following: 1.45 (1.31-1.61), 1.26 (1.16-.37), 1.42 (1.23-1.63), 2.06 (1.36-3.12), 1.93 (1.38-2.69) and 3.30 (1.13-9.67). Compared with chemotherapy alone, all differences were statistically significant. CIK cells could increase the CD3 T cells, CD3 CD4 T cells, NK cells and the ratio of CD4/CD8 T cells. The chemotherapy with CIK cells had a lower risk of hematotoxicity, gastrointestinal toxicity, liver injury and a higher fever than that of chemotherapy alone. The evidence quality was "moderate" to "very low."
CONCLUSIONS
The available moderate evidences indicate that chemotherapy with CIK cells, especially autologous CIK cells, can significantly improve the tumor responses, 1- and 2-year overall and progression-free survival rates in patients with advanced NSCLC. This treatment does have a high risk of fever. The optimal use may be treatment with one or two cycles and in combination with vinorelbine and cisplatin, paclitaxel and cisplatin, or docetaxel and cisplatin.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Carcinoma, Non-Small-Cell Lung; China; Cytokine-Induced Killer Cells; Female; Follow-Up Studies; Humans; Immunity, Cellular; Immunotherapy; Lung Neoplasms; Male; Middle Aged; Progression-Free Survival; Randomized Controlled Trials as Topic; Survival Rate; T-Lymphocytes; Young Adult
PubMed: 30554868
DOI: 10.1016/j.jcyt.2018.10.011 -
Journal of Cancer 2021Different second-line treatments of patients with trastuzumab-resistant human epidermal growth factor receptor 2 (HER2) positive breast cancer were examined in...
Efficacy of second-line treatments for patients with advanced human epidermal growth factor receptor 2 positive breast cancer after trastuzumab-based treatment: a systematic review and bayesian network analysis.
Different second-line treatments of patients with trastuzumab-resistant human epidermal growth factor receptor 2 (HER2) positive breast cancer were examined in randomized controlled trials (RCTs). A network meta-analysis is helpful to evaluate the comparative survival benefits of different options. We performed a bayesian network meta-analysis using R-4.0.0 software and fixed consistency model to compare the progression free survival (PFS) and overall survival (OS) benefits of different second-line regimens. 13 RCTs (19 publications, 4313 patients) remained for qualitative synthesis and 12 RCTs (17 publications, 4022 patients) were deemed eligible for network meta-analysis. For PFS, we divided network analysis into two parts owing to insufficient connections among treatments. The first part involved 8 treatments in 9 studies and we referred it as PFS (#1). Amid the following 8 interventions: pyrotinib + capecitabine, T-DM1 + atezolizumab, pertuzumab + trastuzumab + capecitabine, T-DM1, trastuzumab + capecitabine, lapatinib + capecitabine, neratinib, and capecitabine, we found consistent benefits between the first three interventions; moreover, pyrotinib + capecitabine was most likely to be associated with the best benefits; capecitabine monotherapy was associated with the worst PFS. The second part included 3 treatments in 2 studies and we referred it as PFS (#2): everolimus + trastuzumab + vinorelbine had better PFS benefits versus trastuzumab + vinorelbine and afatinib + vinorelbine. For OS, we analyzed 7 treatments in 7 studies, and observed T-DM1 + atezolizumab, pertuzumab + trastuzumab + capecitabine, and T-DM1 had similar effectiveness, and the first had the highest probability to yield the longest OS; capecitabine or neratinib alone yielded the worst OS benefits. Our work comprehensively summarized and analyzed current available RCT-based evidence of the second-line treatments for trastuzumab-treated, HER2-positive, advanced breast cancer. These results provide clinicians and oncologists meaningful references for clinical drug administration and the development of novel effective therapies.
PubMed: 33613756
DOI: 10.7150/jca.51845