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Critical Reviews in Oncology/hematology Jul 2022To assess comparative effectiveness of adjuvant therapies for renal cell carcinoma and quantify the absolute benefit of adjuvant treatments by clinicopathological risk... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess comparative effectiveness of adjuvant therapies for renal cell carcinoma and quantify the absolute benefit of adjuvant treatments by clinicopathological risk groups.
METHODS
This 'living' review was conducted using Living Interactive Evidence (LIvE) synthesis framework.
RESULTS
The 'living' results are available on an interactive website. This network meta-analysis, including six RCTs with 7525 participants, showed that pembrolizumab (rank 1) significantly improved disease-free survival and overall survival compared with sunitinib but not when compared to pazopanib, and axitinib. The risk of treatment-related grade 3 or higher adverse events was increased with pembrolizumab as compared to placebo and axitinib but not when compared to sunitinib. The absolute benefit of adjuvant pembrolizumab increases substantially with larger tumor size, nodal positivity and higher Leibovich scores.
CONCLUSION
Current evidence suggests that pembrolizumab delays disease progression compared to sunitinib. A risk-adapted strategy should be used in patients undergoing consideration for treatment with adjuvant pembrolizumab.
Topics: Axitinib; Carcinoma, Renal Cell; Humans; Kidney Neoplasms; Network Meta-Analysis; Sunitinib
PubMed: 35537621
DOI: 10.1016/j.critrevonc.2022.103706 -
International Journal of Cancer Jun 2013Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) have been widely used in advanced cancers. Concerns have arisen regarding the risk... (Meta-Analysis)
Meta-Analysis Review
Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) have been widely used in advanced cancers. Concerns have arisen regarding the risk of venous thromboembolism with the use of these drugs. Currently, the contribution of VEGFR-TKIs to venous thromboembolism is still unknown. We performed a meta-analysis to determine the incidence and relative risk (RR) of venous thromboembolism events (VTEs) associated with these agents. Eligible studies included phase II and III prospective trials evaluating US Food and Drug Administration approved VEGFR-TKIs (pazopanib, sunitinib, sorafenib and vandetanib), and data on VTEs were available. Overall incidence rates, RR and 95% confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of included trials. A total of 14 studies (4,430 patients) were selected for this meta-analysis. The incidence of VTEs related to VEGFR-TKIs was 3% (95%CI: 1.7-5.1%), and there was no statistically significant increase in the risk of VTEs for VEGFR-TKIs versus controls in overall population (RR0.912, 95%CI: 0.617-1.348, p = 0.643). On subgroup analysis, no significant increase in the risk of VTEs was found among different VEGFR-TKIs or tumor types. No evidence of publication bias was observed. The use of VEGFR-TKIs does not significantly increase the risk of VTEs, the risk of VTEs in patients with cancer is driven predominantly by tumor types, host factors and concomitant usage of anticancer agents. These results would provide important information for clinicians who use VEGFR-TKIs to treat patients with solid cancer.
Topics: Humans; Incidence; Protein Kinase Inhibitors; Publication Bias; Receptors, Vascular Endothelial Growth Factor; Risk; Venous Thromboembolism
PubMed: 23225494
DOI: 10.1002/ijc.27979 -
Expert Opinion on Pharmacotherapy 2015To conduct a systematic review and network meta-analysis (NMA) to assess effectiveness of first-line treatments for advanced renal cell carcinoma (RCC). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To conduct a systematic review and network meta-analysis (NMA) to assess effectiveness of first-line treatments for advanced renal cell carcinoma (RCC).
METHODS
Database searches were conducted to identify randomized controlled trials (RCTs) reporting results for eligible treatments. A fixed-effect Bayesian NMA was conducted to assess the relative effectiveness of treatments, with progression-free survival (PFS) reported as hazard ratios (HRs) and 95% credible intervals (CrIs).
RESULTS
Eleven unique RCTs were suitable for inclusion in the NMA. In the base case, in terms of PFS, sunitinib was superior compared with bevacizumab + IFN-α (HR = 0.79, 95% CrI: 0.64 - 0.96), everolimus (HR = 0.70, 95% CrI: 0.56 - 0.87), sorafenib (HR = 0.56, 95% CrI: 0.40 - 0.77) and temsirolimus + bevacizumab (HR = 0.74, 95% CrI: 0.56 - 0.96). Although, the point values for the mean and median HRs were < 1.0, there was no significant difference in PFS between sunitinib and axitinib, pazopanib or tivozanib. Although sensitivity analyses impacted the results of the NMA, no treatment was significantly more efficacious than sunitinib.
CONCLUSION
Results from this analysis suggest that there is no treatment superior to the current benchmark treatment, sunitinib, in the management of advanced RCC in the first-line setting.
Topics: Antineoplastic Agents; Bayes Theorem; Carcinoma, Renal Cell; Disease-Free Survival; Humans; Kidney Neoplasms; Randomized Controlled Trials as Topic
PubMed: 26194211
DOI: 10.1517/14656566.2015.1058359 -
British Journal of Clinical Pharmacology Sep 2013To investigate the overall incidence and risk of hypertension in cancer patients who receive axitinib and compare the differences in incidences between axitinib and the... (Meta-Analysis)
Meta-Analysis Review
AIMS
To investigate the overall incidence and risk of hypertension in cancer patients who receive axitinib and compare the differences in incidences between axitinib and the other four approved vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs).
METHODS
Several databases were searched, including Pubmed, Embase and Cochrane databases. Eligible studies were phase II and III prospective clinical trials of patients with cancer assigned axitinib at a starting dose of 5 mg orally twice daily with data on hypertension available. Overall incidence rates, relative risk (RR), and 95% confidence intervals (CI) were calculated employing fixed or random effects models depending on the heterogeneity of the included trials.
RESULTS
A total of 1908 patients from 10 clinical trials were included. The overall incidences of all grade and high grade hypertension in cancer patients were 40.1% (95% CI 30.9, 50.2%) and 13.1% (95% CI 6.7, 24%). The use of axitinib was associated with significantly increased risk of all grade (RR 3.00, 95% CI 1.29, 6.97, P = 0.011) and high grade hypertension (RR 1.71, 95% CI 1.21, 2.43, P = 0.003). The risk of axitinib associated all grade and high grade hypertension in renal cell carcinoma (RCC) was significantly higher than that in non-RCC. Additionally, the risk of hypertension with axitinib was substantially higher than other approved VEGFR-TKIs, while the risk of all grade hypertension with axitinib was similar to pazopanib (RR 1.05; 95% CI 0.95-, 1.17, P = 0.34).
CONCLUSIONS
While sharing a similar spectrum of target receptors with other VEGFR-TKIs, axitinib is associated with an unexpectedly high risk of developing hypertension. Close monitoring and appropriate management for hypertension are recommended during the treatment.
Topics: Antineoplastic Agents; Axitinib; Clinical Trials as Topic; Humans; Hypertension; Imidazoles; Incidence; Indazoles; Molecular Targeted Therapy; Neoplasms; Protein Kinase Inhibitors; Receptors, Vascular Endothelial Growth Factor; Risk
PubMed: 23617405
DOI: 10.1111/bcp.12149 -
Journal of Cancer Research and Clinical... May 2015Vascular endothelial growth factor signaling pathway plays a crucial role in angiogenesis and has become a promising target for cancer drug development. We aimed to... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Vascular endothelial growth factor signaling pathway plays a crucial role in angiogenesis and has become a promising target for cancer drug development. We aimed to quantify the overall efficacy and safety of angiogenesis inhibitors in advanced non-small cell lung cancer (NSCLC).
METHODS
Electronic databases were searched for randomized controlled trials (RCTs) comparing angiogenesis inhibitors with non-angiogenesis inhibitors for NSCLC patients. The extracted data on objective response rates (ORRs), disease control rates (DCRs), progression-free survival (PFS) and overall survival (OS) were pooled. Common adverse events (AEs) were also studied.
RESULTS
A total of 33 RCTs involving 17,396 patients were included. Compared with non-angiogenesis inhibitors, angiogenesis inhibitors resulted in significant improvement in PFS (HR, 0.81; 95 % CI 0.76-0.85; p < 0.001), OS (HR, 0.95; 95 % CI 0.92-0.98; p = 0.004), ORR (RR, 1.54; 95 % CI 1.37-1.73; p < 0.001) and DCR (RR, 1.18; 95 % CI 1.10-1.27; p < 0.001). The AEs associated with angiogenesis inhibitors were generally predictable and manageable.
CONCLUSION
Angiogenesis inhibitors were superior to non-angiogenesis inhibitors in terms of ORR, DCR, PFS and OS in advanced NSCLC patients. Further studies are warranted to explore the predictive biomarkers to pick up those who may gain utmost benefit from anti-angiogenic therapy.
Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Bevacizumab; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Hemorrhage; Humans; Indazoles; Indoles; Lung Neoplasms; Niacinamide; Odds Ratio; Phenylurea Compounds; Piperidines; Pyrimidines; Pyrroles; Quinazolines; Randomized Controlled Trials as Topic; Receptors, Vascular Endothelial Growth Factor; Signal Transduction; Sorafenib; Sulfonamides; Sunitinib; Thrombocytopenia; Treatment Outcome; Vascular Endothelial Growth Factor A; Ramucirumab
PubMed: 25373315
DOI: 10.1007/s00432-014-1862-5 -
Therapeutic Advances in Medical Oncology 2020Effective systemic treatment of non-clear cell renal carcinoma (nccRCC) is still an unmet clinical need, with few studies to support an evidence-based approach. To date,... (Review)
Review
BACKGROUND
Effective systemic treatment of non-clear cell renal carcinoma (nccRCC) is still an unmet clinical need, with few studies to support an evidence-based approach. To date, the only recommended standard first-line treatment is sunitinib. Pazopanib may also be used in nccRCC but its place in therapy is not clearly established. It has comparable efficacy and better tolerability than sunitinib in clear cell renal carcinoma. Our objective was to review the use of pazopanib in metastatic nccRCC.
METHODS
We conducted a systematic review according to PRISMA guidelines. Any type of study reporting the use of pazopanib in metastatic renal cell carcinoma including cases with non-clear cell histology was eligible.
RESULTS
In all, 15 studies were included in our analysis, including a total of 318 nccRCC patients treated with pazopanib. Most studies were retrospective ( = 12); three were prospective trials. The specific outcomes of nccRCC patients were reported by four studies. Pazopanib alone as first-line treatment gave overall response rates ranging from 27% to 33%, disease control rates of 81-89%, median progression free survival of 8.1-16.5 months and median overall survival of 17.3-31.0 months. Grade 3-4 adverse events rates were 21-55%.
CONCLUSION
The present review provides for the first time a systematic summary of evidence about the possible use of pazopanib as first-line treatment for nccRCC, with a favorable outcome despite the low strength of evidence. Pazopanib could be considered as a possible therapeutic option in this setting.
PubMed: 32550862
DOI: 10.1177/1758835920915303 -
Critical Reviews in Oncology/hematology Jul 2013A trial-level meta-analysis was conducted to determine the relative risk (RR) of venous thromboembolic events (VTEs) associated with approved vascular endothelial growth... (Meta-Analysis)
Meta-Analysis Review
Venous thromboembolic events with vascular endothelial growth factor receptor tyrosine kinase inhibitors: a systematic review and meta-analysis of randomized clinical trials.
A trial-level meta-analysis was conducted to determine the relative risk (RR) of venous thromboembolic events (VTEs) associated with approved vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKI). Eligible studies included randomized phase 2 and 3 trials comparing arms with and without a Food and Drug Administration-approved VEGFR TKI (sunitinib, sorafenib, pazopanib, vandetanib, and axitinib). Statistical analyses calculated the RR and 95% confidence intervals (CI), using random-effects or fixed-effects models based on heterogeneity. A total of 7441 patients from 9 phase III trials and 8 phase II trials were selected. The RR of all grade and high-grade VTEs for the TKI vs. no TKI arms was 1.10 (95% CI 0.73-1.66, p=0.64) and 0.85 (95% CI: 0.58-1.25, p=0.41), respectively. No difference in risk was found based on tumor type, age and trial design. The majority of trials exhibited high quality per Jadad scoring and no heterogeneity or publication bias was found.
Topics: Antineoplastic Agents; Humans; Neoplasms; Protein Kinase Inhibitors; Publication Bias; Randomized Controlled Trials as Topic; Receptors, Vascular Endothelial Growth Factor; Risk; Venous Thromboembolism
PubMed: 23317774
DOI: 10.1016/j.critrevonc.2012.12.006 -
PloS One 2016Hyponatraemia has been reported with targeted therapies in cancer patients. Aim of the study was to perform an up-to-date meta-analysis in order to determine the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hyponatraemia has been reported with targeted therapies in cancer patients. Aim of the study was to perform an up-to-date meta-analysis in order to determine the incidence and relative risk (RR) in cancer patients treated with these agents.
MATERIALS AND METHODS
The scientific literature regarding hyponatraemia was extensively reviewed using MEDLINE, PubMed, Embase and Cochrane databases. Eligible studies were selected according to PRISMA statement. Summary incidence, RR, and 95% Confidence Intervals were calculated using random-effects or fixed-effects models based on the heterogeneity of selected studies.
RESULTS
4803 potentially relevant trials were identified: of them, 13 randomized phase III studies were included in this meta-analysis. 6670 patients treated with 8 targeted agents were included: 2574 patients had hepatocellular carcinoma, whilst 4096 had other malignancies. The highest incidences of all-grade hyponatraemia were observed with the combination of brivanib and cetuximab (63.4) and pazopanib (31.7), while the lowest incidence was reported by afatinib (1.7). The highest incidence of high-grade hyponatraemia was reported by cetuximab (34.8), while the lowest incidences were reported by gefitinib (1.0). Summary RR of developing all-grade and high-grade hyponatraemia with targeted agents was 1.36 and 1.52, respectively. The highest RRs of all-grade and high-grade hyponatraemia were associated with brivanib (6.5 and 5.2, respectively). Grouping by drug category, the RR of high-grade hyponatraemia with angiogenesis inhibitors was 2.69 compared to anti-Epidermal Growth Factor Receptors agents (1.12).
CONCLUSION
Treatment with biological therapy in cancer patients is associated with a significant increased risk of hyponatraemia, therefore frequent clinical monitoring should be emphasized when managing targeted agents.
Topics: Clinical Trials, Phase III as Topic; Humans; Hyponatremia; Incidence; Neoplasms; Randomized Controlled Trials as Topic; Risk Factors
PubMed: 27167519
DOI: 10.1371/journal.pone.0152079 -
BMC Cancer Aug 2013Current guidelines recommend anthracycline-based chemotherapy primarily with doxorubicin either as monotherapy or in combination with ifosfamide as the first-line... (Review)
Review
BACKGROUND
Current guidelines recommend anthracycline-based chemotherapy primarily with doxorubicin either as monotherapy or in combination with ifosfamide as the first-line treatment for most advanced STS subtypes. Therapeutic options after failure of doxorubicin and/or ifosfamide are limited. This study aimed to comprehensively review available data on the activity and safety of interventions in second- or later-line treatment of advanced STS.
METHODS
Electronic literature databases (Embase®, MEDLINE®, MEDLINE® In-Process, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews) were searched from 1980 to 01 March 2012 to identify randomised controlled trials (RCTs) and non-randomised studies (both prospective and retrospective) evaluating pharmacological interventions in patients with advanced STS pre-treated with anthracycline- and/or ifosfamide-based therapy.
RESULTS
The review identified six RCTs (one phase III and five phase II trials) and 94 non-randomised studies. Based on the primary trial endpoints, RCTs demonstrated favourable efficacy for pazopanib over placebo (PFS: 4.6 months vs. 1.6 months), gemcitabine plus dacarbazine over dacarbazine monotherapy (3-month PFS rate: 54.2% vs. 35.2%), and trabectedin 3-weekly schedule over weekly schedule (TTP: 3.7 months vs. 2.3 months. The non-randomised studies demonstrated heterogeneity in efficacy and safety results.
CONCLUSIONS
Across the RCTs, pazopanib over placebo, gemcitabine-dacarbazine over dacarbazine, and trabectedin 3-weekly over weekly regimen clearly demonstrated a PFS advantage in the second- and later-line treatment of advanced STS. With only one phase III trial in this setting, there is a clear need for additional comparative trials to better understand the risk: benefit ratios of available agents and combinations.
Topics: Antineoplastic Agents; Dacarbazine; Deoxycytidine; Dioxoles; Humans; Indazoles; Pyrimidines; Randomized Controlled Trials as Topic; Sarcoma; Sulfonamides; Tetrahydroisoquinolines; Trabectedin; Treatment Failure; Gemcitabine
PubMed: 23937858
DOI: 10.1186/1471-2407-13-385 -
Critical Reviews in Oncology/hematology Mar 2014The use of vascular-endothelial growth factor (VEGF) antibody bevacizumab is associated with an increased risk of gastrointestinal (GI) perforation, but the incidence... (Meta-Analysis)
Meta-Analysis Review
Risk of gastrointestinal perforation in cancer patients treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors: a systematic review and meta-analysis.
BACKGROUND
The use of vascular-endothelial growth factor (VEGF) antibody bevacizumab is associated with an increased risk of gastrointestinal (GI) perforation, but the incidence and risk of GI perforation associated with vascular endothelial growth factor tyrosine-kinase inhibitors (VEGFR-TKIs) has not been well described. We conduct a systematic review and meta-analysis of published trials to evaluate the overall incidence and risk of GI perforation associated with VEGFR-TKIs.
METHODS
Databases from PubMed, Web of Science and abstracts presented at ASCO meeting up to March 31, 2013 were searched to identify relevant studies. Eligible studies included prospective phase II and III trials evaluating VEGFR-TKIs in cancer patients with adequate data on GI perforation. Statistical analyses were conducted to calculate the summary incidence, odds ratio (OR) and 95% confidence intervals (CIs) by using either random effects or fixed effect models according to the heterogeneity of included studies.
RESULTS
A total of 5352 patients with a variety of solid tumors from 20 clinical trials were included in our analysis. The incidence of GI perforation was 1.3% (95%CI: 0.8-2.0%) among patients receiving VEGFR-TKIs, with a mortality of 28.6% (15.0-47.6%). Patients treated with VEGFR-TKIs did not significantly increase the risk of GI perforation compared with patients treated with control medication, with an OR of 2.99 (95%CI: 0.85-10.53, p=0.089). Sub-group analysis showed that the incidence of GI perforation did not significantly vary with tumor types, VEGFR-TKIs and treatments regimens. No evidence of publication bias was observed.
CONCLUSIONS
The use of VEGFR-TKIs dose not significantly increase the risk of GI perforation in comparison with the controls. Further studies are recommended to investigate this association and the risk differences among different tumor types, VEGFR-TKIs or treatment regimens.
Topics: Humans; Intestinal Perforation; Neoplasms; Protein Kinase Inhibitors; Receptors, Vascular Endothelial Growth Factor
PubMed: 24182420
DOI: 10.1016/j.critrevonc.2013.10.002