-
Sarcoma 2016This systematic literature review describes adverse events (AEs) among patients with soft tissue sarcoma (STS) who received second-line or later anticancer therapies.... (Review)
Review
This systematic literature review describes adverse events (AEs) among patients with soft tissue sarcoma (STS) who received second-line or later anticancer therapies. Searches were conducted in PubMed, EMBASE, and Cochrane Central Register of Controlled Trials for studies of adults with advanced or metastatic STS who received systemic anticancer therapy before enrollment in a randomized-controlled trial of pazopanib, another targeted cancer agent, or cytotoxic chemotherapy. Of 204 publications identified, seven articles representing six unique studies met inclusion criteria. Additional safety results for pazopanib were identified on ClinicalTrials.gov. Hematologic toxicities were common with all therapies evaluated (pazopanib, trabectedin, dacarbazine ± gemcitabine, gemcitabine ± docetaxel, cyclophosphamide, and ifosfamide). Studies differed in AE type, timing of assessment, and outcomes reported, although patient populations and AE assessment timing were relatively similar for pazopanib and trabectedin. AEs that were more common with trabectedin than pazopanib were anemia, neutropenia, nausea/vomiting, and elevations in aspartate aminotransferase and alanine aminotransferase. An AE that was more common with pazopanib than trabectedin was anorexia. Only the pazopanib study reported AE frequencies versus placebo. A planned meta-analysis was not feasible, as there was no common comparator. More well-designed studies that include common comparators are needed for comparison of safety effects among treatments for STS.
PubMed: 27516726
DOI: 10.1155/2016/3597609 -
Frontiers in Pharmacology 2022Multiple targeted therapeutics are available for radioiodine-refractory differentiated thyroid cancer (RAIR-DTC), but it remains unclear which treatment is optimal to...
Multiple targeted therapeutics are available for radioiodine-refractory differentiated thyroid cancer (RAIR-DTC), but it remains unclear which treatment is optimal to achieve long-term survival. A systematic search of the PubMed, Embase, and ClinicalTrials.gov databases was conducted to identify eligible randomized controlled trials (RCTs) comparing the efficacy and safety of targeted treatments for patients with RAIR-DTC from inception to April, 2022. Data were extracted by following the recommendations of the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. We calculated the odds ratio (OR) or hazard ratio (HR), its corresponding 95% credible intervals (CrI), and the surface under the cumulative ranking curve (SUCRA) to indicate ranking probability using Bayesian network meta-analyses. The primary outcome was progression-free survival (PFS). The secondary outcomes were overall survival (OS), objective response rate (ORR), disease control rate (DCR), and grade 3 or higher adverse events. A total of 12 eligible RCTs involved 1,959 patients and 13 treatments: apatinib, cabozantinib, anlotinib, nintedanib, lenvatinib, lenvatinib with low dose (LD), sorafenib, sorafenib plus everolimus, donafenib (200 mg), donafenib (300 mg), pazopanib (continuous), pazopanib (intermittent), and vandetanib. Pooled analyses indicated that targeted therapeutics significantly prolonged PFS and OS in patients with RAIR-DTC (0.31, 0.21-0.41; 0.69, 0.53-0.85, respectively) compared with placebo. Network meta-analyses indicated that lenvatinib showed the most favorable PFS, with significant differences versus sorafenib (0.33, 0.23-0.48), vandetanib (0.31, 0.20-0.49), nintedanib (0.30, 0.15-0.60), and placebo (0.19, 0.15-0.25), while apatinib was most likely to be ranked first for prolonging OS with a SUCRA of 0.90. Lenvatinib showed the highest ORR (66%, 61%-70%), followed by anlotinib (59%, 48%-70%) and apatinib (54%, 40%-69%). Lenvatinib caused the most adverse events of grade 3 or higher, followed by lenvatinib (LD) and apatinib. Different toxicity profiles of individual treatment were also revealed. This network meta-analysis suggests that lenvatinib and apatinib were associated with the best progression-free survival and overall survival benefits, respectively, for patients with RAIR-DTC, compared with other targeted therapeutics. Patients who received lenvatinib or apatinib also had more grade 3 or higher adverse events. : [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=302249], identifier [CRD42022302249].
PubMed: 36091770
DOI: 10.3389/fphar.2022.933648 -
Critical Reviews in Oncology/hematology May 2015A systematic review and meta-analysis was conducted to determine the relative risk (RR) of congestive heart failure (CHF) associated with approved multi-targeted... (Meta-Analysis)
Meta-Analysis Review
A systematic review and meta-analysis was conducted to determine the relative risk (RR) of congestive heart failure (CHF) associated with approved multi-targeted vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKI). Eligible studies included randomized trials comparing arms with and without an FDA-approved VEGFR TKI. Statistical analyses calculated the relative risk (RR) and 95% confidence intervals (CI). A total of 10,647 patients from 16 phase III trials and 5 phase II trials were selected. All grade CHF occurred in 138 of 5752 (2.39%) patients receiving VEGFR TKIs and 37 of 4895 (0.75%) patients in the non-TKI group. High-grade CHF occurred in 17 of 1426 (1.19%) patients receiving VEGFR TKIs and 8 of 1232 (0.65%) patients in the non-TKI group. The RR of all grade and high-grade CHF for the TKI vs. no TKI arms was 2.69 (p<0.001; 95% CI: 1.86 to 3.87) and 1.65 (p=0.227, 95% CI: 0.73 to 3.70), respectively. The RR of relatively specific TKIs (axitinib) was similar to relatively non-specific TKIs (sunitinib, sorafenib, vandetanib, pazopanib).
Topics: Antineoplastic Agents; Heart Failure; Humans; Neoplasms; Odds Ratio; Protein Kinase Inhibitors; Publication Bias; Randomized Controlled Trials as Topic; Receptors, Vascular Endothelial Growth Factor; Risk
PubMed: 25577572
DOI: 10.1016/j.critrevonc.2014.12.008 -
European Journal of Cancer (Oxford,... Jul 2015Drug-induced liver chemistry abnormalities, primarily transaminase elevations, are commonly observed in pazopanib-treated patients. This meta-analysis characterises... (Meta-Analysis)
Meta-Analysis Review
Characterisation of liver chemistry abnormalities associated with pazopanib monotherapy: a systematic review and meta-analysis of clinical trials in advanced cancer patients.
Drug-induced liver chemistry abnormalities, primarily transaminase elevations, are commonly observed in pazopanib-treated patients. This meta-analysis characterises liver chemistry abnormalities associated with pazopanib. Data of pazopanib-treated patients from nine prospective trials were integrated (N=2080). Laboratory datasets were used to characterise the incidence, timing, recovery and patterns of liver events, and subsequent rechallenge with pazopanib. Severe cases of liver chemistry abnormalities were clinically reviewed. Multivariate analyses identified predisposing factors. Twenty percent of patients developed elevated alanine aminotransferase (ALT) >3×ULN. Incidence of peak ALT >3-5×ULN, >5-8×ULN, >8-20×ULN and >20×ULN was 8%, 5%, 5% and 1%, respectively. Median time to onset for all events was 42days; 91% of events were observed within 18weeks. Recovery rates based on peak ALT >3-5×ULN, >5-8×ULN, >8-20×ULN and >20×ULN were 91%, 90%, 90% and 64%, respectively. Median time from onset to recovery was 30days, but longer in patients without dose interruption. Based on clinical review, no deaths were associated with drug-induced liver injury. Overall, 38% of rechallenged patients had ALT elevation recurrence, with 9-day median time to recurrence. Multivariate analysis showed that older age was associated with development of ALT >8×ULN. There was no correlation between hypertension and transaminitis. Our data support the current guidelines on regular liver chemistry tests after initiation of pazopanib, especially during the first 9 or 10weeks, and also demonstrate the safety of rechallenge with pazopanib.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Alanine Transaminase; Chemical and Drug Induced Liver Injury; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Female; Humans; Indazoles; Liver; Male; Middle Aged; Neoplasms; Pyrimidines; Randomized Controlled Trials as Topic; Sulfonamides; Young Adult
PubMed: 25899987
DOI: 10.1016/j.ejca.2015.03.019 -
Cancers Oct 2022Cancer is a clinical condition that can benefit from anti-angiogenic drugs (AADs). Given the low prevalence and the heterogeneity of childhood cancers, information about... (Review)
Review
Cancer is a clinical condition that can benefit from anti-angiogenic drugs (AADs). Given the low prevalence and the heterogeneity of childhood cancers, information about the safety of these drugs in pediatric patients is partially assessed. The aim of this study was to evaluate the safety of AADs in pediatric patients with solid tumors. Clinical trials and observational studies were searched in PubMed, ISI Web of Science, and ClinicalTrials database For each included study, adverse events (AEs) were extracted. A meta-analysis was conducted by pooling proportions of AEs using a random intercept logistic regression model. Seventy studies were retrieved. Most part were clinical trials (55 out of 70), and only fifteen observational studies were found. Overall, proportion of serious and non-serious AEs of AADs used as monotherapy was 46% and 89%, respectively. Proportions of serious AEs varied among drugs: sunitinib, 79%; lenvatinib, 64%; sorafenib, 48%; ramucirumab, 41%; pazopanib, 30%; and vandetanib, 27%. A higher proportion of non-serious hematological AEs was found in the patients receiving pazopanib with respect to sunitinib and lenvatinib. The safety profile of AADs has been extensively investigated for mostly drugs in phase I and II trials and is limited to acute toxicities. Overall, one out of two patients using AAD drugs in monotherapy experienced a serious AE despite proportions varied per single drugs. When AADs were combined with standard chemotherapy, the proportion of AEs varied in relation to the single combinations.
PubMed: 36358734
DOI: 10.3390/cancers14215315 -
American Journal of Clinical Oncology Jun 2023Patients with recurrent or persistent ovarian cancer often have poor prognoses, and their optimal treatment regimen remains unclear. Inhibition of angiogenesis is a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients with recurrent or persistent ovarian cancer often have poor prognoses, and their optimal treatment regimen remains unclear. Inhibition of angiogenesis is a valuable strategy for treating ovarian cancer, and the drug pazopanib is a potent, multitarget tyrosine kinase inhibitor. However, treatment with pazopanib in combination with chemotherapy remains controversial. We performed a systematic review and meta-analysis to clarify the efficacy and side effects of pazopanib combined with chemotherapy in the treatment of advanced ovarian cancer.
METHODS
The PubMed, Embase, and Cochrane databases were systematically searched for relevant randomized controlled trials published up to September 2, 2022. The primary outcomes of eligible studies included overall response rate (ORR), disease control rate, 1-year progression-free survival (PFS) rate, 2-year PFS rate, 1-year overall survival (OS) rate, 2-year OS rate, and adverse events.
RESULT
Outcomes from a total of 518 recurrent or persistent ovarian cancer patients from 5 studies were analyzed in this systematic review. Pooled results showed that pazopanib plus chemotherapy, when compared with chemotherapy alone, significantly improved the ORR (pooled risk ratio=1.400; 95% CI, 1.062-1.846; P = 0.017) but not the disease control rate, 1-year PFS, 2-year PFS, 1-year OS, or 2-year OS. Moreover, pazopanib increased the risk of neutropenia, hypertension, fatigue, and liver dysfunction.
CONCLUSION
Pazopanib plus chemotherapy improved patient ORR but did not improve survival; it also increased the occurrence of several adverse events. Further large-sample clinical trials are needed to verify these results to guide pazopanib use in patients with ovarian cancer.
Topics: Humans; Female; Ovarian Neoplasms; Pyrimidines; Sulfonamides; Indazoles; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36877187
DOI: 10.1097/COC.0000000000000999 -
European Journal of Endocrinology May 2015Many tyrosine kinase inhibitors (TKIs) have been studied in patients with thyroid carcinoma (TC). However, the effect and toxicity of various TKIs in differentiated TC... (Meta-Analysis)
Meta-Analysis Review
Therapy of endocrine disease: response and toxicity of small-molecule tyrosine kinase inhibitors in patients with thyroid carcinoma: a systematic review and meta-analysis.
CONTEXT
Many tyrosine kinase inhibitors (TKIs) have been studied in patients with thyroid carcinoma (TC). However, the effect and toxicity of various TKIs in differentiated TC (DTC) and medullary TC (MTC) patients have not been directly compared. The aim of the present systematic review and meta-analysis was to systematically summarize response and toxicity of TKIs in TC patients.
METHODS
All major databases were systematically searched for publications on TKIs in TC. Primary endpoint was objective response; secondary endpoints were clinical benefit, percentage TKI dose reduction/discontinuation, hand-foot syndrome, diarrhea, and nausea/vomiting. Meta-analysis was performed using an exact likelihood approach and a logistic regression. Pooled percentages and 95% CIs were reported.
RESULTS
In total, 22 publications were included. For DTC patients, gefitinib induced no objective responses. Pooled percentage was highest for pazopanib, 49 (95% CI 33-64)%, and was 17 (95% CI 12-24)% for sorafenib. For MTC, gefitinib and imatinib induced no objective responses, whereas sunitinib induced objective response in 43 (95% CI 14-77)%. For vandetanib and cabozantinib, these numbers were 40 (95% CI 34-46)% and 27 (95% CI 22-32)% respectively. Clinical benefit was found in 53 (95% CI 48-59)% of DTC patients on sorafenib, and in 84 (95% CI 79-88)% and 55 (95% CI 49-61)% of MTC patients on vandetanib and cabozantinib respectively. All TKIs were associated with considerable toxicity.
CONCLUSION
The currently studied TKIs show a modest response, while side effects are not negligible. Therefore, we suggest to solely consider TKIs in TC patients with rapid progressive disease, for whom the benefits of treatment outweigh toxicity.
Topics: Antineoplastic Agents; Humans; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Thyroid Neoplasms
PubMed: 25572389
DOI: 10.1530/EJE-14-0788 -
Frontiers in Oncology 2020Several phase-II trials have been designed to evaluate tyrosine kinase inhibitors (TKIs), in particular, pazopanib in neuroendocrine neoplasia (NEN), but its efficacy...
Several phase-II trials have been designed to evaluate tyrosine kinase inhibitors (TKIs), in particular, pazopanib in neuroendocrine neoplasia (NEN), but its efficacy has not yet been demonstrated in a randomised-controlled Phase III trial. A systematic review of the published clinical trials of metastatic NEN patients could reduce the possible bias of single phase II studies. The present systematic review focuses on the efficacy and safety of pazopanib in patients with metastatic and locally advanced NEN. A systematic search in the major databases Medline/PubMed, Cochrane and Embase and in supplementary material from important international Meetings was performed to identify publications on pazopanib for the treatment of neuroendocrine neoplasia. English language was defined as a restriction. Four authors of the present review independently performed the study selection, assessed the risk of bias and extracted study data. Four published clinical trials and 2 abstracts were identified. One trial was excluded because the topic was Von-Hippel Landau disease and one abstract was eliminated because of the lack of information on meeting proceedings. In all of the trials pazopanib was orally administered at a dose of 800 mg daily continuously with a 28-day cycle. The intention-to-treat population for efficacy was composed of 230 patients with a median age of 62 years. The partial response rate was 10.7% (95% confidence interval 2.6-20.5). The rate for stable disease was 79.6% (range: 61.7-92.1%) with a disease control rate (DCR) of 90.3%. Progressive disease was reported in 9.7% (range 5.2-17.6) of patients. No complete responses were observed. Median progression-free survival was 11.6 months (95% CI: 9.2-13.9). Overall survival from all the trials was 24.6 (95% CI: 18.7-40.8) months. Severe adverse events (grade III-IV) included hypertension 31%, 16% increase in AST/ALT, diarrhoea 10% and fatigue 10%. Pazopanib monotherapy achieved a DCR of 90.3% in patients with locally advanced and/or metastatic neuroendocrine neoplasia, with an overall response rate comparable to other TKIs and mTOR inhibitors and a safety profile similar to that of drugs of the same class.
PubMed: 32318336
DOI: 10.3389/fonc.2020.00414 -
Expert Review of Clinical Pharmacology Aug 2016Cabozantinib (XL184) is an oral inhibitor of multiplereceptor tyrosine kinases including mesenchymal-epithelial transition factor (MET) and vascular endothelial growth... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Cabozantinib (XL184) is an oral inhibitor of multiplereceptor tyrosine kinases including mesenchymal-epithelial transition factor (MET) and vascular endothelial growth factor receptor 2 (VEGFR2). Hypertension is one of its major side effects, but the incidence rate and overall risk has not been systematically studied. We thus conducted this meta-analysis to investigate the overall incidence and risk of developing hypertension in cancer patients treated with cabozantinib.
AREAS COVERED
Pubmed, Embase and oncology conference proceedings were searched for relevant studies. Eligible studies were phase II and III prospective clinical trials of cabozantinib in cancer patients with data on hypertension available. A total of 1,514 patients (cabozantinib, 1083; control, 431) with a variety of solid tumors from 8 prospective clinical trials were included for the meta-analysis. The use of cabozantinib was associated with significantly increased risk of developing all grade (RR 5.48; 95%CI, 3.76-7.99; p < 0.001) and high grade (5.09; 95% CI: 2.71-9.54, p < 0.001) hypertension in comparison with controls. Additionally, the risk of high grade hypertension with cabozantinib was substantially higher than other four approved VEGFR-TKIs (sorafenib, sunitinib, vandetanib and pazopanib). Expert commentary: Cancer patients receiving cabozantinib have an increased risk of developing hypertension. Close monitoring and management of hypertension are recommended.
Topics: Anilides; Antineoplastic Agents; Clinical Trials as Topic; Humans; Hypertension; Incidence; Neoplasms; Protein Kinase Inhibitors; Pyridines; Risk
PubMed: 27181268
DOI: 10.1080/17512433.2016.1190269 -
Clinical Genitourinary Cancer Jun 2017This systematic review and meta-analysis was accomplished with the purpose of evaluating the risk of encountering selected hair changes in patients with cancer receiving... (Comparative Study)
Comparative Study Meta-Analysis Review
Risk of Distinctive Hair Changes Associated With Pazopanib in Patients With Renal Cell Carcinoma (RCC) Versus Patients Without RCC: A Comparative Systematic Review and Meta-analysis.
OBJECTIVE
This systematic review and meta-analysis was accomplished with the purpose of evaluating the risk of encountering selected hair changes in patients with cancer receiving pazopanib.
METHODS
We favored relevant prospective randomized phase II and III trials that assessed pazopanib in patients with cancer, depicting various hair-related changes, as eligible for inclusion.
RESULTS
After elimination of ineligible studies, a total of 11 clinical trials were regarded as eligible for the meta-analysis. The relative risk of all-grade alopecia and hair color changes was 1.75 (95% confidence interval, 1.33-2.31; P < .0001) and 4.54 (95% confidence interval, 3.67-5.62; P < .00001), respectively. Subgroup analyses of hair color changes according to the type of cancer treated revealed significant differences between renal cell carcinoma and non-renal cell carcinoma studies (P = .01).
CONCLUSIONS
Our meta-analysis has established that pazopanib-based treatment can be significantly correlated to an elevated risk of all grade alopecia and hair color changes compared with controls.
Topics: Alopecia; Angiogenesis Inhibitors; Carcinoma, Renal Cell; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Female; Hair Color; Humans; Indazoles; Kidney Neoplasms; Male; Prospective Studies; Pyrimidines; Randomized Controlled Trials as Topic; Sulfonamides
PubMed: 28189432
DOI: 10.1016/j.clgc.2016.12.018