-
Scientific Reports Mar 2022The efficacy of anti-angiogenic agents (AAAs) in epithelial ovarian cancer (EOC) remains unclear. Therefore, we conducted a systematic review and network meta-analysis... (Meta-Analysis)
Meta-Analysis
The efficacy of anti-angiogenic agents (AAAs) in epithelial ovarian cancer (EOC) remains unclear. Therefore, we conducted a systematic review and network meta-analysis (NMA) to synthesize evidence of their comparative effectiveness for improving overall survival (OS) among EOC patients. We searched six databases for randomized controlled trials (RCTs) from their inception to February 2021. We performed an NMA with hazard ratios (HRs) and 95%-confidence intervals (CIs) to evaluate comparative effectiveness among different AAAs in chemotherapy-naïve and recurrent EOC. P-score was used to provide an effectiveness hierarchy ranking. Sensitivity NMA was carried out by focusing on studies that reported high-risk chemotherapy-naïve, platinum-resistant, and platinum-sensitive EOC. The primary outcome was OS. We identified 23 RCTs that assessed the effectiveness of AAAs. In recurrent EOC, concurrent use of trebananib (10 mg/kg) with chemotherapy was likely to be the best option (P-score: 0.88, HR 1.67, 95% CI 0.94; 2.94). The NMA indicated that bevacizumab plus chemotherapy followed by maintenance bevacizumab (P-score: 0.99) and pazopanib combined with chemotherapy (P-score: 0.79) both had the highest probability of being the best intervention for improving OS in high-risk chemotherapy-naïve and platinum-resistant EOC, respectively. AAAs may not play a significant clinical role in non-high-risk chemotherapy-naïve and platinum-sensitive EOC.
Topics: Angiogenesis Inhibitors; Bevacizumab; Carcinoma, Ovarian Epithelial; Female; Humans; Neoplasm Recurrence, Local; Network Meta-Analysis; Ovarian Neoplasms
PubMed: 35264616
DOI: 10.1038/s41598-022-07731-1 -
Current Drug Targets 2016Sporadic data are available about pazopanib use in patients with metastatic renal cell carcinoma (mRCC) undergoing dialysis and no systematic review has been previously... (Review)
Review
BACKGROUND
Sporadic data are available about pazopanib use in patients with metastatic renal cell carcinoma (mRCC) undergoing dialysis and no systematic review has been previously performed about this issue.
OBJECTIVE
The objective of the present mini-review is to provide an overview of clinical outcomes of pazopanib in this population, in order to support the clinical oncologist for the treatment choice and management.
RESULTS
All the literature ever published about mRCC dialysis patients receiving pazopanib, until August 2015, was evaluated: only two case series emerged from our search and one more patient from our department was also included, with a total of 11 mRCC dialysis patients overall. Moreover, we described our case of intrapatient dose titration of pazopanib during dialysis.
CONCLUSION
The continued treatment schedule, the short half-life, the predominantly hepatic metabolism, the wide possibility of dose modulation, the favorable tolerability profile and the similar efficacy respect to sunitinib represent factors in favor of pazopanib as first line mRCC treatment in dialysis patients. The knowledge and the good management of toxicity during pazopanib treatment can lead, also in dialysis patients, to the best and longest application of the drug, taking into account the concept of a dose escalation guided by toxicity as a marker of efficacy. The review, together with our single case report, confirmed the efficacy, the good tolerability and the maneuverability of pazopanib treatment in mRCC patients undergoing dialysis.
Topics: Adult; Angiogenesis Inhibitors; Carcinoma, Renal Cell; Dose-Response Relationship, Drug; Half-Life; Humans; Indazoles; Kidney Failure, Chronic; Kidney Neoplasms; Male; Pyrimidines; Renal Dialysis; Sulfonamides; Treatment Outcome
PubMed: 26758665
DOI: 10.2174/1389450117666160112114756 -
Journal of the American Academy of... Nov 2017The discovery of signaling networks that drive oncogenic processes has led to the development of targeted anticancer agents. The burden of pigmentary adverse events from... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The discovery of signaling networks that drive oncogenic processes has led to the development of targeted anticancer agents. The burden of pigmentary adverse events from these drugs is unknown.
OBJECTIVE
To conduct a systematic review and meta-analysis of published clinical trials and determine the incidence and risk of development of targeted therapy-induced pigmentary changes.
METHODS
A comprehensive search was conducted to identify studies reporting targeted therapy-induced pigmentary changes. The incidence and relative risk were calculated. Case reports and series were reviewed to understand clinical characteristics.
RESULTS
A total of 8052 patients from 36 clinical trials were included. The calculated overall incidences of targeted cancer therapy-induced all-grade pigmentary changes in the skin and hair were 17.7% (95% confidence interval [CI], 11.9-25.4) and 21.5% (95% CI, 14.9-30.1), respectively. The relative risk of all-grade pigmentary changes of skin and hair were 93.7 (95% CI, 5.86-1497.164) and 20.1 (95% CI, 8.35-48.248). Across 53 case reports/series (N = 75 patients), epidermal growth factor receptor and breakpoint cluster region-abelson inhibitors were the most common offending agents.
LIMITATIONS
Potential under-reporting and variability in oncologists reporting these events.
CONCLUSION
There is a significant risk of development of pigmentary changes during treatment with targeted anticancer therapies. Appropriate counseling and management are critical to minimize psychosocial impairment and deterioration in quality of life.
Topics: Antineoplastic Agents; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Molecular Targeted Therapy; Neoplasms; Pigmentation Disorders; Prevalence; Prognosis; Quality of Life; Randomized Controlled Trials as Topic; Risk Assessment
PubMed: 28918974
DOI: 10.1016/j.jaad.2017.06.044 -
Cancer Research and Treatment Oct 2017Despite advancements in therapy for advanced gastric and gastroesophageal junction cancers, their prognosis remains dismal. Tumor angiogenesis plays a key role in cancer... (Review)
Review
Despite advancements in therapy for advanced gastric and gastroesophageal junction cancers, their prognosis remains dismal. Tumor angiogenesis plays a key role in cancer growth and metastasis, and recent studies indicate that pharmacologic blockade of angiogenesis is a promising approach to therapy. In this systematic review, we summarize current literature on the clinical benefit of anti-angiogenic agents in advanced gastric cancer. We conducted a systematic search of PubMed and conference proceedings including the American Society of Clinical Oncology, the European Society for Medical Oncology, and the European Cancer Congress. Included studies aimed to prospectively evaluate the efficacy and safety of anti-angiogenic agents in advanced gastric or gastroesophageal junction cancer. Each trial investigated at least one of the following endpoints: overall survival, progression-free survival/time to progression, and/or objective response rate. Our search yielded 139 publications. Forty-two met the predefined inclusion criteria. Included studies reported outcomes with apatinib, axitinib, bevacizumab, orantinib, pazopanib, ramucirumab, regorafenib, sorafenib, sunitinib, telatinib, and vandetanib. Second-line therapy with ramucirumab and third-line therapy with apatinib are the only anti-angiogenic agents so far shown to significantly improve survival of patients with advanced gastric cancer. Overall, agents that specifically target the vascular endothelial growth factor ligand or receptor have better safety profile compared to multi-target tyrosine kinase inhibitors.
Topics: Angiogenesis Inhibitors; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Clinical Trials as Topic; Esophageal Neoplasms; Esophagogastric Junction; Humans; Molecular Targeted Therapy; Neoplasm Staging; Protein Kinase Inhibitors; Quality of Life; Receptor, ErbB-2; Stomach Neoplasms; Treatment Outcome; Vascular Endothelial Growth Factor A
PubMed: 28052652
DOI: 10.4143/crt.2016.176 -
The Oncologist Dec 2017Prognosis for patients with metastatic soft tissue sarcomas (STS) is dismal, with median overall survival (OS) of 8-12 months. The role of second-line therapy has been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Prognosis for patients with metastatic soft tissue sarcomas (STS) is dismal, with median overall survival (OS) of 8-12 months. The role of second-line therapy has been inconsistently investigated over the last 20 years. This systematic review and meta-analysis was performed to assess the efficacy of salvage treatment in pretreated adult type STS, gastrointestinal stromal tumor (GIST) excluded.
MATERIAL AND METHODS
PubMed, Web of Science, SCOPUS, EMBASE, CINAHL, and The Cochrane Library were searched for randomized phase II/phase III trials exploring second- or beyond therapy lines in pretreated metastatic STS. Two independent investigators extracted data; the quality of eligible studies was resolved by consensus. Hazard ratio (HR) of death and progression (OS and progression-free survival [PFS]) and odds ratio (OR) for response rate (RR) were pooled in a fixed- or random-effects model according to heterogeneity. Study quality was assessed with the Cochrane's risk of bias tool, and publication bias with funnel plots.
RESULTS
Overall, 10 randomized trials were selected. The pooled HR for death was 0.81 (95% confidence interval [CI] 0.73-0.9). Second-line therapy reduced the risk of progression by 49% (HR = 0.51, 95% CI 0.34-0.76). This translated into an absolute benefit in OS and PFS by 3.3 and 1.6 months, respectively. Finally, RR with new agents or chemotherapy doublets translated from 4.3% to 7.6% (OR = 1.78, 95% CI 1.22-2.50).
CONCLUSION
Better survival is achieved in patients treated with salvage therapies (chemotherapy, as single or multiple agents or targeted biological agents). A 3-months gain in OS and an almost double RR is observed. Second lines also attained a reduction by 50% the risk of progression.
IMPLICATIONS FOR PRACTICE
There is some evidence that salvage therapies after first-line failure are able to improve outcome in metastatic soft tissue sarcoma (STS). Trabectedin, gemcitabine-based therapy, and pazopanib are currently approved drugs used after conventional upfront treatment. This meta-analysis reviews the benefit of new agents used in randomized trials in comparison with no active treatments or older agents for recurrent/progressed STS. The results show that modern drugs confer a statistically significant 3-month benefit in terms of overall survival, and an increase in response rate. Despite a limited improvement in outcome, currently approved second-line therapy should be offered to patients with good performance status.
Topics: Disease-Free Survival; Doxorubicin; Humans; Randomized Controlled Trials as Topic; Salvage Therapy; Sarcoma
PubMed: 28835514
DOI: 10.1634/theoncologist.2016-0474 -
Frontiers in Oncology 2023There are a variety of treatment options for recurrent platinum-resistant ovarian cancer, and the optimal specific treatment still remains to be determined. Therefore,...
BACKGROUND
There are a variety of treatment options for recurrent platinum-resistant ovarian cancer, and the optimal specific treatment still remains to be determined. Therefore, this Bayesian network meta-analysis was conducted to investigate the optimal treatment options for recurrent platinum-resistant ovarian cancer.
METHODS
Pubmed, Cochrane, Embase, and Web of Science were searched for articles published until 15 June 2022. The outcome measures for this meta-analysis were overall survival (OS), progression-free survival (PFS), and adverse events (AEs) of Grade 3-4. The Cochrane assessment tool for risk of bias was used to evaluate the risk of bias of the included original studies. The Bayesian network meta-analysis was conducted. This study was registered on PROSPERO (CRD42022347273).
RESULTS
Our systematic review included 11 RCTs involving 1871 patients and 11 treatments other than chemotherapy. The results of meta-analysis showed that the overall survival (OS) was the highest in adavosertib + gemcitabine compared with conventional chemotherapy, (HR=0.56,95%CI:0.35-0.91), followed by sorafenib + topotecan (HR=0.65, 95%CI:0.45-0.93). In addition, Adavosertib + Gemcitabine regimen had the highest PFS (HR=0.55,95%CI:0.34-0.88), followed by Bevacizumab + Gemcitabine regimen (HR=0.48,95%CI:0.38-0.60) and the immunotherapy of nivolumab was the safest (HR=0.164,95%CI:0.312-0.871) with least adverse events of Grades 3-4.
CONCLUSIONS
The results of this study indicated that Adavosertib (WEE1 kinase-inhibitor) + gemcitabine regimen and Bevacizumab + Gemcitabine regimen would be significantly beneficial to patients with recurrent platinum-resistant ovarian cancer, and could be preferred for recurrent platinum-resistant ovarian cancer. The immunotherapeutic agent, Nivolumab, is of considerable safety, with a low risk for grade-III or IV adverse events. Its safety is comparable to Adavosertib + gemcitabine regimen. Pazopanib + Paclitaxel (weekly regimen), Sorafenib + Topotecan/Nivolumab could be selected if there are contraindications of the above strategies.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42022347273.
PubMed: 37114128
DOI: 10.3389/fonc.2023.1114484 -
Computational and Mathematical Methods... 2022The aim of this systematic evaluation and meta-analysis was to analyze the efficacy and adverse effects of adjuvant targeted therapy regimens in advanced or metastatic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The aim of this systematic evaluation and meta-analysis was to analyze the efficacy and adverse effects of adjuvant targeted therapy regimens in advanced or metastatic renal cell carcinoma (RCC).
METHODS
Studies eligible for the efficacy of adjuvant targeted therapy regimens in advanced or metastatic RCC published before December 2021 in PubMed, Embase, Cochrane Clinical Trials Database (CENTRAL), and Web of Science were searched for (1) patients with locally advanced renal cell carcinoma (RCC) who received adjuvant postoperative targeted therapy versus those not receiving active treatment; (2) primary endpoint outcomes of disease-free survival (DFS), overall survival (OS), and adverse events (AEs); and (3) design: randomized controlled trial (RCT) as inclusion criteria. Data on DFS and OS were extracted or recalculated by meta-analysis as hazard ratios (HRs), and AEs were compared using a dominance ratio (OR).
RESULT
This systematic evaluation will provide evidence on the effectiveness and adverse effects of adjuvant targeted therapy in patients with advanced RCC. The results of meta-analysis showed that all of the three adjuvant targeted therapeutic drugs (sorafenib, sunitinib, and pazopanib) did not benefit from the adjuvant targeted therapy for DFS and OS and even increase the incidence of AEs compared to the placebo.
CONCLUSIONS
The aim of this study was to summarize data on DFS, OS, and AEs in patients with advanced RCC treated with targeted therapies. The evidence provided by this systematic evaluation and meta-analysis will help guide clinical decision-making and provide insight into the future management of patients with advanced RCC.
Topics: Carcinoma, Renal Cell; Chemotherapy, Adjuvant; Combined Modality Therapy; Disease-Free Survival; Humans; Kidney Neoplasms
PubMed: 35392587
DOI: 10.1155/2022/7341294 -
Expert Opinion on Pharmacotherapy Jan 2013A systematic review/meta-analysis was conducted to assess the effectiveness and safety of second-line treatments for advanced renal cell carcinoma (RCC), which includes... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
A systematic review/meta-analysis was conducted to assess the effectiveness and safety of second-line treatments for advanced renal cell carcinoma (RCC), which includes the vascular endothelial growth factor inhibitor axitinib.
METHODS
Database searches were conducted to identify randomised controlled trials (RCTs). Indirect comparisons using a fixed-effect Bayesian model were used to assess the relative effectiveness of treatments and reported as hazard ratio (HR) and 95% credible intervals (CrI).
RESULTS
Although 24 RCTs met eligibility criteria, only three studies were included in the fixed-effect Bayesian meta-analysis, due to differences in patient inclusion criteria/reported outcomes in the wider dataset. Robust meta-analysis was restricted to the subgroup pretreated with cytokines. In terms of progression-free survival (PFS), axitinib was superior compared with placebo (HR = 0.25, 95% CrI: 0.17 - 0.38), sorafenib (HR = 0.46, 95% CrI: 0.32 - 0.68) and pazopanib (HR = 0.47, 95% CrI: 0.26 - 0.85). An analysis including all patients, regardless of previous first-line treatment, reported similar results. There was no significant difference in PFS between sorafenib and pazopanib.
CONCLUSION
Results from the present study suggest that axitinib will be an important treatment option to extend PFS in the management of advanced RCC in the second-line setting. Ongoing research will define the optimal treatment algorithm leading to a patient-focused treatment strategy.
Topics: Adult; Aged; Aged, 80 and over; Angiogenesis Inhibitors; Antineoplastic Agents; Axitinib; Bayes Theorem; Carcinoma, Renal Cell; Disease Progression; Disease-Free Survival; Female; Humans; Imidazoles; Indazoles; Kidney Neoplasms; Male; Middle Aged; Neoplasm Staging; Niacinamide; Phenylurea Compounds; Pyrimidines; Randomized Controlled Trials as Topic; Sorafenib; Sulfonamides; Treatment Outcome; Young Adult
PubMed: 23256638
DOI: 10.1517/14656566.2013.758713 -
Investigational New Drugs Jun 2013Axitinib is a potent, selective vascular endothelial growth factor receptor (VEGFR) inhibitor. We have performed a systematic analysis to investigate the risk of... (Meta-Analysis)
Meta-Analysis Review
Axitinib is a potent, selective vascular endothelial growth factor receptor (VEGFR) inhibitor. We have performed a systematic analysis to investigate the risk of hand-foot skin reaction (HFSR) to axitinib and compare the differences in incidences between sorafenib, sunitinib, pazopanib and axitinib. Relevant studies were identified from PubMed (1998-2012). Eligible studies were limited to prospective Phase II-III clinical trials in which cancer patients were treated with axitinib monotherapy at a starting dose of 5 mg orally twice daily. Incidence, relative risk (RR), and 95 % confidence intervals were calculated using random-effects or fixed-effects models based on heterogeneity of included studies. A total of 984 patients from 6 prospective clinical trials were included in the analysis. The overall incidence of all-grade and high-grade HFSR was 29.2 % (95 % CI: 14.0-51.1 %) and 9.6 % (95 % CI: 4.2-20.7 %), respectively. The relative risks of all-grade and high-grade HFSR to axitinib compared to sorafenib were decreased for all-grade (RR=0.54, 95 % CI: 0.44-0.65, p<0.001) and high-grade HFSR (RR=0.31, 95 % CI: 0.19-0.52, p<0.001). The risk of all-grade and high-grade HFSR to axitinib, sunitinib and sorafenib was significantly higher as compared to pazopanib (RR=6.49, 95 % CI: 4.65-9.05, p<0.001; RR=6.40, 95 % CI: 3.60-11.37, p<0.001, and RR=4.20, 95 % CI: 3.07-5.75, p<0.001; RR=3.67, 95 % CI: 2.15-6.24, p<0.001, and RR=7.51, 95 % CI: 5.5-10.3, p<0.001; RR=5.93, 95 % CI: 3.5-10.0, p<0.001, respectively). Similar to sorafenib and sunitinib, axitinib is associated with a significant risk of HFSR, despite having an increased specificity for VEGF receptors. These findings underscore the importance of supportive dermatologic care in patients treated with axitinib, in order to maintain quality of life, adherence, and persistence to therapy.
Topics: Axitinib; Hand-Foot Syndrome; Humans; Imidazoles; Incidence; Indazoles; Protein Kinase Inhibitors; Receptors, Vascular Endothelial Growth Factor; Risk
PubMed: 23345001
DOI: 10.1007/s10637-013-9927-x -
Clinical Genitourinary Cancer Dec 2019Pazopanib is a protein tyrosine kinase inhibitor that limits tumor growth through angiogenesis inhibition. The use of other protein tyrosine kinase inhibitors,...
Pazopanib is a protein tyrosine kinase inhibitor that limits tumor growth through angiogenesis inhibition. The use of other protein tyrosine kinase inhibitors, specifically sunitinib, within non-clear cell renal cell carcinoma (nccRCC) has led to increased survival with a decreased adverse event profile. The data for the treatment of nccRCC is limited, with most studies evaluating the use of sunitinib. Therefore, the evaluation of pazopanib is of particular clinical interest in the treatment of nccRCC. The objective of this systematic review was to assess the efficacy and safety of pazopanib for nccRCC. PubMed (1946 to April 2019) and Embase (1947 to April 2019) were queried using the search term combination: protein tyrosine kinase inhibitor or pazopanib and non clear cell renal cell carcinoma or non-clear cell renal cell carcinoma. Studies evaluating clinical outcomes of pazopanib for nccRCC were included, represented by 3 retrospective cohort studies and 1 single-arm, open-label prospective study. In patients with advanced or metastatic nccRCC, treatment with pazopanib resulted in positive effects for multiple markers of efficacy, including progression-free survival, overall survival, and objective response rates. The median duration of follow-up ranged from 11.8 months to 24.4 months. Pazopanib was well-tolerated in most studies. The most commonly reported adverse events were fatigue, diarrhea, and hypertension. Pazopanib appears to be an effective and safe option for the treatment of advanced or metastatic nccRCC. Future investigation with larger randomized controlled trials is warranted to further define the role of pazopanib in patients with nccRCC.
Topics: Angiogenesis Inhibitors; Carcinoma, Renal Cell; Clinical Trials as Topic; Diarrhea; Fatigue; Humans; Hypertension; Indazoles; Kidney Neoplasms; Progression-Free Survival; Protein Kinase Inhibitors; Pyrimidines; Sulfonamides
PubMed: 31585694
DOI: 10.1016/j.clgc.2019.09.001