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Targeted Oncology May 2024Targeting of angiogenesis has become a major therapeutic approach for the treatment of various advanced cancers. There are many unresolved questions on the toxicity of...
BACKGROUND
Targeting of angiogenesis has become a major therapeutic approach for the treatment of various advanced cancers. There are many unresolved questions on the toxicity of anti-angiogenic tyrosine kinase inhibitors (TKIs).
OBJECTIVE
We performed a meta-analysis to assess the toxicity prevalence of the different anti-angiogenic TKIs among cancer patients and in subpopulations of interest including patients with renal cell carcinoma.
PATIENTS AND METHODS
We searched the MEDLINE and Cochrane Library databases to November 2023. Clinical trials were eligible if they set out to report the grade ≥3 toxicities related to one of the seven currently approved anti-angiogenic TKIs as monotherapies. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method was applied with PROSPERO (CRD42023411946).
RESULTS
The 421 eligible studies included a total of 56,895 cancer patients treated with anti-angiogenic TKI monotherapy. Twenty-four different cancer types were identified, mainly renal cell carcinoma (41.9% of the patients). The anti-angiogenic TKI was sorafenib (34.5% of the patients), sunitinib (30.5%), regorafenib (10.7%), pazopanib (9.4%), cabozantinib (7.7%), axitinib (4.3%), and lenvatinib (2.9%). The pooled prevalence of grade 3 and 4 toxicities was 56.1% (95% confidence interval 53.5-58.6), with marked between-study heterogeneity (I = 96.8%). Toxicity profiles varied considerably depending on the type of TKI, the cancer type, and the specific patient characteristics. In particular, Asian patients and elderly people had higher prevalences of severe toxicities, with pazopanib being the best-tolerated drug. For patients treated with sunitinib, particularly those with metastatic RCC, there was no significant difference in terms of toxicity according to the regimen schedule.
CONCLUSIONS
This meta-analysis highlights the toxicity profiles of anti-angiogenic TKI monotherapies, and thus enables high-level recommendations for the choice of anti-angiogenic TKIs on the basis of the patient's age, ethnicity, comorbidities, and comedications, for personalized treatment.
PubMed: 38761350
DOI: 10.1007/s11523-024-01067-8 -
Journal of Clinical Pharmacy and... Feb 2021Metastatic renal cell carcinoma (mRCC) is the most common type of kidney cancers. Disease-specific survival for mRCC has been significantly improved with the... (Meta-Analysis)
Meta-Analysis
WHAT IS KNOWN AND OBJECTIVE
Metastatic renal cell carcinoma (mRCC) is the most common type of kidney cancers. Disease-specific survival for mRCC has been significantly improved with the introduction of new targeted agents since 2005. However, there is a lack of head-to-head clinical trials comparing the efficacy between therapies. This study compared indirectly progression-free survival (PFS) and overall survival (OS) among first-line and second-line therapies in patients with mRCC using network meta-analysis (NMA).
METHODS
The PubMed, MEDLINE, Cochrane Library and Web of Science were searched to identify phase II or phase III randomized controlled trials (RCTs) of targeted and biological therapies in patients with mRCC published between January 2000 and June 2020. The Bayesian fixed-effect NMA was performed to evaluate relative PFS and OS of first-line and second-line therapies of axitinib, bevacizumab, cabozantinib, everolimus, lenvatinib, nivolumab, ipilimumab, pazopanib, sorafenib, sunitinib, temsirolimus, tivozanib, avelumab and pembrolizumab, which were approved by the Food and Drug Administration or European Medicines Agency. End points were compared using hazard ratio (HR) and 95% credible interval (CrI). The surface under the cumulative ranking curve (SUCRA) was estimated to assess the probability of being the best treatment.
RESULTS AND DISCUSSION
A total of 26 RCTs (first line: 19, second line: 9) with 13 893 patients were included in the NMA. For the first-line therapy, cabozantinib was associated with the highest improved PFS (HR = 0.26, 95% CrI = 0.14-0.44) followed by avelumab + axitinib and pembrolizumab + axitinib (HR = 0.27, SUCRA = 90%). Pembrolizumab + axitinib had a high likelihood of being the preferred treatment when using OS as the outcome measure (HR = 0.41, 95% CrI = 0.16-0.85). Avelumab + axitinib had the lowest HR compared with placebo + interferon on discontinuations due to AE (HR = 1.04, 95% CrI = 0.54-1.86). For second-line therapy, cabozantinib was identified as the most effective treatment option when assessing PFS (HR = 0.17, 95% CrI = 0.12-0.24). Axitinib had the lowest HR of OS and discontinuation due to AE (HR = 0.54, 95% CrI = 0.40-0.71; HR = 0.98, 95% CrI = 0.42-1.97, respectively). Pazopanib was the second choice in terms of OS (HR = 0.56, 95% CrI = 0.28-1.00; SUCRA = 76%) compared with placebo.
WHAT IS NEW AND CONCLUSION
With respect to PFS and OS improvement, cabozantinib, avelumab + axitinib and pembrolizumab + axitinib are likely to be the preferred options for the first-line therapy and cabozantinib and axitinib for the second-line therapy in the management of mRCC. Regarding safety, avelumab + axitinib and temsirolimus were considered preferred treatment options in first-line and second-line therapies. More future research is needed to establish subgroup analyses, allowing evaluation of the impact of some of the differences in patient characteristics, including treatment effect modifiers.
Topics: Anilides; Antineoplastic Agents; Carcinoma, Renal Cell; Disease-Free Survival; Humans; Kidney Neoplasms; Neoplasm Metastasis; Network Meta-Analysis; Pyridines
PubMed: 33112003
DOI: 10.1111/jcpt.13282 -
The Cochrane Database of Systematic... Mar 2021Cervical cancer ranks as the fourth leading cause of death from cancer in women. Historically, women with metastatic or recurrent cervical cancer have had limited... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cervical cancer ranks as the fourth leading cause of death from cancer in women. Historically, women with metastatic or recurrent cervical cancer have had limited treatment options. New anti-angiogenesis therapies, such as vascular endothelial growth factor (VEGF) targeting agents, offer an alternative strategy to conventional chemotherapy; they act by inhibiting the growth of new blood vessels, thereby restricting tumour growth by blocking the blood supply.
OBJECTIVES
To assess the benefits and harms of VEGF targeting agents in the management of persistent, recurrent, or metastatic cervical cancer.
SEARCH METHODS
We performed searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, online registers of clinical trials, and abstracts of scientific meetings up until 27 May 2020.
SELECTION CRITERIA
We examined randomised controlled trials (RCTs) that evaluated the use of VEGF targeting agents alone or in combination with conventional chemotherapy or other VEGF targeting agents.
DATA COLLECTION AND ANALYSIS
Three review authors independently screened the results of search strategies, extracted data, assessed risk of bias, and analysed data according to the standard methods expected by Cochrane. The certainty of evidence was assessed via the GRADE approach.
MAIN RESULTS
A total of 1634 records were identified. From these, we identified four studies with a total of 808 participants for inclusion. We also identified two studies that were awaiting classification and nine ongoing studies. Bevacizumab plus chemotherapy versus chemotherapy Treatment with bevacizumab plus chemotherapy may result in lower risk of death compared to chemotherapy alone (hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.62 to 0.95; 1 study, 452 participants; low-certainty evidence). However, there are probably more specific adverse events when compared to chemotherapy alone, including gastrointestinal perforations or fistulae (risk ratio (RR) 18.00, 95% CI 2.42 to 133.67; 1 study, 440 participants; moderate-certainty evidence); serious thromboembolic events (RR 4.5, 95% CI 1.55 to 13.08; 1 study, 440 participants; moderate-certainty evidence); and hypertension (RR 13.75, 95% CI 5.07 to 37.29; 1 study, 440 participants; moderate-certainty evidence). There may also be a higher incidence of serious haemorrhage (RR 5.00, 95% CI 1.11 to 22.56; 1 study, 440 participants; low-certainty evidence). In addition, the incidence of serious adverse events is probably higher (RR 1.44, 95% CI 1.16 to 1.79; 1 study, 439 participants; moderate-certainty evidence). The incremental cost-effectiveness ratio was USD 295,164 per quality-adjusted life-year (1 study, 452 participants; low-certainty evidence). Cediranib plus chemotherapy versus chemotherapy Treatment with cediranib plus chemotherapy may or may not result in similar risk of death when compared to chemotherapy alone (HR 0.94, 95% CI 0.53 to 1.65; 1 study, 69 participants; low-certainty evidence). We found very uncertain results for the incidences of specific adverse events, including gastrointestinal perforations or fistulae (RR 3.27, 95% CI 0.14 to 77.57; 1 study, 67 participants; very low-certainty evidence); serious haemorrhage (RR 5.45, 95% CI 0.27 to 109.49; 1 study, 67 participants; very low-certainty evidence); serious thromboembolic events (RR 3.41, 95% CI 0.14 to 80.59; 1 study, 60 participants; very low-certainty evidence); and serious hypertension (RR 0.36, 95% CI 0.02 to 8.62; 1 study, 67 participants; very low-certainty evidence). In addition, there may or may not be a similar incidence of serious adverse events compared to chemotherapy alone (RR 1.15, 95% CI 0.75 to 1.78; 1 study, 67 participants; low-certainty evidence). Apatinib plus chemotherapy or chemotherapy/brachytherapy versus chemotherapy or chemotherapy/brachytherapy Treatment with apatinib plus chemotherapy or chemotherapy/brachytherapy may or may not result in similar risk of death compared to chemotherapy alone or chemotherapy/brachytherapy alone (HR 0.90, 95% CI 0.51 to 1.60; 1 study, 52 participants; low-certainty evidence). However, hypertension events may occur at a higher incidence as compared to chemotherapy alone or chemotherapy/brachytherapy alone (RR 5.14, 95% CI 1.28 to 20.73; 1 study, 52 participants; low-certainty evidence). Pazopanib plus lapatinib versus lapatinib Treatment with pazopanib plus lapatinib may result in higher risk of death compared to lapatinib alone (HR 2.71, 95% CI 1.16 to 6.31; 1 study, 117 participants; low-certainty evidence). We found very uncertain results for the incidences of specific adverse events, including gastrointestinal perforations or fistulae (RR 2.00, 95% CI 0.19 to 21.59; 1 study, 152 participants; very low-certainty evidence); haemorrhage (RR 2.00, 95% CI 0.72 to 5.58; 1 study, 152 participants; very low-certainty evidence); and thromboembolic events (RR 3.00, 95% CI 0.12 to 72.50; 1 study, 152 participants; very low-certainty evidence). In addition, the incidence of hypertension events is probably higher (RR 12.00, 95% CI 2.94 to 49.01; 1 study, 152 participants; moderate-certainty evidence). There may or may not be a similar incidence of serious adverse events as compared to lapatinib alone (RR 1.45, 95% CI 0.94 to 2.26; 1 study, 152 participants; low-certainty evidence). Pazopanib versus lapatinib Treatment with pazopanib may or may not result in similar risk of death as compared to lapatinib (HR 0.96, 95% CI 0.67 to 1.38; 1 study, 152 participants; low-certainty evidence). We found very uncertain results for the incidences of specific adverse events, including gastrointestinal perforations or fistulae (RR 1.03, 95% CI 0.07 to 16.12; 1 study, 150 participants; very low-certainty evidence); haemorrhage (RR 1.03, 95% CI 0.31 to 3.40; 1 study, 150 participants; very low-certainty evidence); and thromboembolic events (RR 3.08, 95% CI 0.13 to 74.42; 1 study, 150 participants; very low-certainty evidence). In addition, the incidence of hypertension events is probably higher (RR 11.81, 95% CI 2.89 to 48.33; 1 study, 150 participants; moderate-certainty evidence). The risk of serious adverse events may or may not be similar as compared to lapatinib (RR 1.31, 95% CI 0.83 to 2.07; 1 study, 150 participants; low-certainty evidence).
AUTHORS' CONCLUSIONS
We found low-certainty evidence in favour of the use of bevacizumab plus chemotherapy. However, bevacizumab probably increases specific adverse events (gastrointestinal perforations or fistulae, thromboembolic events, hypertension) and serious adverse events. We found low-certainty evidence that does not support the use of cediranib plus chemotherapy, apatinib plus chemotherapy, apatinib plus chemotherapy/brachytherapy, or pazopanib monotherapy. We found low-certainty evidence suggesting that pazopanib plus lapatinib worsens outcomes. The VEGF inhibitors apatinib and pazopanib may increase the probability of hypertension events.
Topics: Adult; Aged; Aged, 80 and over; Angiogenesis Inhibitors; Antineoplastic Agents; Bevacizumab; Bias; Brachytherapy; Combined Modality Therapy; Confidence Intervals; Female; Gastric Fistula; Gastrointestinal Hemorrhage; Humans; Hypertension; Indazoles; Intestinal Fistula; Intestinal Perforation; Lapatinib; Middle Aged; Neoplasm Recurrence, Local; Progression-Free Survival; Pyridines; Pyrimidines; Quality of Life; Quinazolines; Randomized Controlled Trials as Topic; Sulfonamides; Thromboembolism; Uterine Cervical Neoplasms; Vascular Endothelial Growth Factor A; Young Adult
PubMed: 33661538
DOI: 10.1002/14651858.CD013348.pub2 -
European Urology Nov 2018Contradictory data exist with regard to adjuvant vascular endothelial growth factor receptor (VEGFR)-targeted therapy in surgically managed patients for localized renal... (Meta-Analysis)
Meta-Analysis
CONTEXT
Contradictory data exist with regard to adjuvant vascular endothelial growth factor receptor (VEGFR)-targeted therapy in surgically managed patients for localized renal cell carcinoma (RCC).
OBJECTIVE
To systematically evaluate the current evidence regarding the therapeutic benefit (disease-free survival [DFS] and overall survival [OS]) and grade 3-4 adverse events (AEs) for adjuvant VEGFR-targeted therapy for resected localized RCC.
EVIDENCE ACQUISITION
A critical review of PubMed/Medline, Embase, and the Cochrane Library in January 2018 according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement was performed. We identified reports and reviewed them according to the Consolidated Standards of Reporting Trials and Standards for the Reporting of Diagnostic Accuracy Studies criteria. Of eight full-text articles that were eligible for inclusion, five studies (two of five were updated analyses) were retained in the final synthesis. Study characteristics were abstracted and the number needed to treat (NNT) per trial was estimated.
EVIDENCE SYNTHESIS
The three randomized controlled phase III trials included the following comparisons: sunitinib versus placebo or sorafenib versus placebo (Adjuvant Sorafenib or Sunitinib for Unfavorable Renal Carcinoma [ASSURE] study, n=1943), sunitinib versus placebo (S-TRAC, n=615), and pazopanib versus placebo (Pazopanib As Adjuvant Therapy in Localized/Locally Advanced RCC After Nephrectomy study, n=1135). The NNT ranged from 10 (S-TRAC) to 137 (ASSURE study). The pooled analysis showed that VEGFR-targeted therapy was not statistically significantly associated with improved DFS (hazard ratio [HR]: 0.92, 95% confidence interval [CI]: 0.82-1.03, p=0.16) or OS (HR: 0.98, 95% CI: 0.84-1.15, p=0.84) compared with the control group. The adjuvant therapy group experienced significantly higher odds of grade 3-4 AEs (OR: 5.89, 95% CI: 4.85-7.15, p<0.001). In exploratory analyses focusing on patients who started on the full-dose regimen, DFS was improved in patients who received adjuvant therapy (HR: 0.83, 95% CI: 0.73-0.95, p=0.005).
CONCLUSIONS
This pooled analysis of reported randomized trials did not reveal a statistically significant effect between adjuvant VEGFR-targeted therapy and improved DFS or OS in patients with intermediate/high-risk local or regional fully resected RCC. Improvement in DFS may be more likely with the use of full-dose regimens, pending further results. However, adjuvant treatment was associated with high-grade AEs.
PATIENT SUMMARY
Vascular endothelial growth factor receptor-targeted therapy after nephrectomy for localized kidney cancer is not associated with consistent improvements in delaying cancer recurrence or prolonging life and comes at the expense of potentially significant side effects.
Topics: Angiogenesis Inhibitors; Carcinoma, Renal Cell; Chemotherapy, Adjuvant; Clinical Trials, Phase III as Topic; Disease Progression; Disease-Free Survival; Humans; Kidney Neoplasms; Neoplasm Recurrence, Local; Neovascularization, Pathologic; Nephrectomy; Progression-Free Survival; Randomized Controlled Trials as Topic; Receptors, Vascular Endothelial Growth Factor; Risk Factors; Signal Transduction; Time Factors; Vascular Endothelial Growth Factor A
PubMed: 29784193
DOI: 10.1016/j.eururo.2018.05.002 -
BMC Urology Jun 2019Conflicting evidence exists regarding the effect of hypertension on the prognosis of metastatic renal cell carcinoma (mRCC) patients treated with tyrosine kinase... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Conflicting evidence exists regarding the effect of hypertension on the prognosis of metastatic renal cell carcinoma (mRCC) patients treated with tyrosine kinase inhibitors (TKIs). This study aimed to assess the predictive value of TKIs-induced hypertension in patients with mRCC.
METHODS
This study was registered in PROSPERO (CRD42019129593). PubMed, Embase, Web of Science and the Cochrane Library database were searched with terms: "renal cell carcinoma", "hypertension", "blood pressure", "tyrosine kinase inhibitor", "sunitinib", "axitinib", "sorafenib" and "pazopanib" until March 21, 2019. Hazard Ratios (HR) and 95% confidence intervals (CI) for progression-free survival (PFS) or overall survival (OS) were extracted and analyzed with Stata 15.0 software. Heterogeneity was assessed using the I value. Meta-regression, subgroup analysis and sensitivity analysis were also performed to explore heterogeneity. Publication bias was assessed with funnel plots and precisely assessed by Egger's and Begg's tests. The quality of evidence of outcomes was generated according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE).
RESULTS
A total of 4661 patients from 22 studies were included in the study. The results showed that the increase of blood pressure was an effective predictor for longer PFS (HR = 0.59, 95% CI: 0.48-0.71, p < 0.001; I = 77.3%) and OS (HR = 0.57, 95% CI: 0.45-0.70, p < 0.001; I = 77.4%) of patients with mRCC. Subgroup analysis revealed that patients receiving sunitinib and pazopanib could have longer PFS and OS.
CONCLUSIONS
This study indicated that TKIs-induced hypertension may be a good predictor for better prognosis of patients with mRCC receiving TKIs treatment, especially using sunitinib or pazopanib.
Topics: Carcinoma, Renal Cell; Disease-Free Survival; Humans; Hypertension; Kidney Neoplasms; Prognosis; Protein Kinase Inhibitors; Survival Rate
PubMed: 31174518
DOI: 10.1186/s12894-019-0481-5 -
Frontiers in Pharmacology 2024The CDK 4/6 inhibitors, including palbociclib and ribociclib, are the standard first-line treatment for hormone receptor-positive (HR+) and human epidermal growth factor...
BACKGROUND
The CDK 4/6 inhibitors, including palbociclib and ribociclib, are the standard first-line treatment for hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer. Proton pump inhibitors are one of the most globally prescribed types of medications as part of the treatment for gastroesophageal reflux and heartburn complaints. Medication interactions have been demonstrated, leading to a decrease in the effectiveness of chemotherapy drugs such as capecitabine and pazopanib. However, their role and interaction with targeted therapies such as CDK inhibitors are still poorly understood.
METHODS
We searched PubMed, Embase and Web of Science databases for studies that investigated the use of PPI with CDK 4/6 inhibitors versus CDK4/6 alone for advanced or metastatic breast cancer. We systematically searched for the currently available CDK inhibitors: palbociclib, ribociclib and abemaciclib. We computed hazard ratios (HRs), with 95% confidence intervals (CIs). We used DerSimonian and Laird random-effect models for all endpoints. Heterogeneity was assessed using I statistics. R, version 4.2.3, was used for statistical analyses.
RESULTS
A total of 2,737 patients with advanced breast cancer in 9 studies were included, with six studies described the status menopausal as 217 (7.9%) pre-menopause and 1851 (67.6%) post-menopause, for endocrine sensitivity only five studies described1489 (54.4%) patients were endocrine-sensitive and 498 (182%) endocrine-resistent, 910 (33.2%) patients used PPIs. The overall Progression-Free Survival was in favor of the PPI non-users (HR 2.0901; 95% CI 1.410-2.9498; < 0.001). As well as the subgroup taking palbociclib, revealing statistical relevance for the PPI non-users (HR 2.2539; 95% CI 1.3213-3.8446; = 0.003) and ribociclib subgroup with a slight decrease in hazard ratio (HR 1.74 95% CI 1.02-2.97; = 0.04; I = 40%). In the multivariate analysis, there was no statistical signifance with ECOG (HR 0.9081; 95% CI 0.4978-16566; p 0.753) and Age (HR 1.2772; 95% CI 0.8790-1.8559; = 0.199). Either, the univariate analysis did not show statistical significance.
CONCLUSION
Women with HR+ and HER2-advanced metastatic breast undergoing treatment with targeted therapies, specifically CDK 4/6 inhibitors, should be monitored for the use of proton pump inhibitors. Therefore, the use of PPIs should be discussed, weighing the advantages and disadvantages for specific cases. It should be individualized based on the necessity in clinical practice for these cases.
SYSTEMATIC REVIEW REGISTRATION
identifier CRD42023484755.
PubMed: 38769999
DOI: 10.3389/fphar.2024.1352224 -
European Journal of Cancer (Oxford,... Sep 2021The efficacy of tyrosine kinase inhibitor (TKI)-based therapy after previous immuno-oncology therapy (IO) failure has been addressed before. However, summary efficacy... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The efficacy of tyrosine kinase inhibitor (TKI)-based therapy after previous immuno-oncology therapy (IO) failure has been addressed before. However, summary efficacy estimates have never been generated in these reports. We addressed this void.
MATERIAL AND METHODS
We systematically examined TKI efficacy after IO-failure and generated weighted median progression-free survival (PFS) estimates for Pazopanib, Axitinib, Cabozantinib, Sunitinib. A systematic review according to PRISMA was conducted. PubMed and abstracts were queried. Only studies proving median PFS were included. Weighted medians were computed for each TKI alternative.
RESULTS
Of 245 articles, nine eligible studies were included in the current study with 952 analysed patients. Weighted PFS medians after any previous IO-based therapy were respectively 13.7 (range from 4.6 to 24.4), 8.1 (range from 4.7 to 13.2), 8.5 (range from 4.7 to 15.2) and 6.9 months (range from 2.9 to 11.6) for Pazopanib, Axitinib, Cabozantinib, Sunitinib. Specific second-line weighted PFS median was 14.8 months (range from 5.6 to 24.4), 10.1 months (range from 6.4 to 13.2), 8.7 months (range from 4.7 to 15.2) and 6.0 months (range from 2.9 to 8.0) for Pazopanib, Axitinib, Cabozantinib, Sunitinib, respectively, after first-line IO.
CONCLUSION
Pazopanib results in the longest weighted median PFS, after previous IO-failure, regardless of treatment line, as well as in specific second-line, post-first-line IO failure settings. Pending novel studies, Pazopanib appears to represent the most promising treatment option after prior IO.
Topics: Female; Humans; Kidney Neoplasms; Male; Neoplasm Metastasis; Protein Kinase Inhibitors; Time Factors
PubMed: 34392067
DOI: 10.1016/j.ejca.2021.07.014 -
European Urology Oncology Jun 2018The role of antiangiogenic agents in advanced renal cell carcinoma (RCC) is well established. However, it is still not clear whether this benefit can be extrapolated to...
CONTEXT
The role of antiangiogenic agents in advanced renal cell carcinoma (RCC) is well established. However, it is still not clear whether this benefit can be extrapolated to the adjuvant setting.
OBJECTIVE
To determine the efficacy and safety of antiangiogenic agents in patients with RCC and a high risk of relapse after nephrectomy.
EVIDENCE ACQUISITION
We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs) evaluating the use of any oral antiangiogenic agent compared to placebo in post-nephrectomy RCC patients. Prespecified data elements were extracted from each trial. Outcomes of interest included overall survival (OS) and disease-free survival (DFS). The overall effect was pooled using the DerSimonian and Laird random-effects models.
EVIDENCE SYNTHESIS
Three RCTs comparing antiangiogenics to placebo among 3693 patients met our inclusion criteria and were used in meta-analyses. Overall, antiangiogenics did not improve DFS (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.78-1.07) or OS (HR 0.99, 95% CI 0.79-1.25). These results persisted when restricting the analysis to patients with clear cell carcinoma and patients with highest risk of relapse. Similarly, sunitinib did not show any improvement in the entire cohort for either DFS (HR 0.89, 95% CI 0.67-1.19) or OS (HR 1.11, 95% CI 0.90-1.37).
CONCLUSIONS
In this meta-analysis, antiangiogenics did not improve OS and DFS over placebo in high-risk RCC after nephrectomy. Further studies are needed to identify the patient population that might derive a benefit from antiangiogenics in the adjuvant setting.
PATIENT SUMMARY
In this article, we found that there is currently insufficient evidence to support the use of oral antiangiogenics in nonmetastatic renal cell carcinoma after nephrectomy. In addition, the use of oral antiangiogenics was associated with a 2.7-fold higher rate of significant side effects compared to placebo.
PubMed: 30345423
DOI: 10.1016/j.euo.2018.03.012 -
Therapeutic Drug Monitoring Jun 2023Dried blood spot (DBS) sampling is a convenient alternative to whole-blood sampling for therapeutic drug monitoring (TDM) in clinical practice. The aim of this study was...
BACKGROUND
Dried blood spot (DBS) sampling is a convenient alternative to whole-blood sampling for therapeutic drug monitoring (TDM) in clinical practice. The aim of this study was to systematically review studies that have examined and used DBS sampling for the TDM of chemotherapy and targeted therapy agents for the treatment of patients with solid cancers.
METHODS
Using the PRISMA guidelines, a systematic literature search of EMBASE and PUBMED was performed to identify eligible clinical studies that used DBS sampling to monitor chemotherapy or targeted therapy for the treatment of solid cancers.
RESULTS
Of the 23 eligible studies, 3 measured concordance between drug concentrations determined by DBS and whole-blood, 7 developed analytical methods of DBS, and 13 performed both. DBS was employed for the TDM of everolimus (3 studies), vemurafenib (2 studies), pazopanib (2 studies), abiraterone (2 studies), mitotane, imatinib, adavosertib, capecitabine, 5-fluorouracil, gemcitabine, cyclophosphamide, ifosfamide, etoposide, irinotecan, docetaxel, gefitinib, palbociclib/ribociclib, and paclitaxel (one study each). The studies included a median of 14 participants (range: 6-34), with 10-50 μL of blood dispensed on DBS cards (20) and Mitra devices (3). Seventeen of the 20 studies that used DBS found no significant impact of the hematocrit on the accuracy and precision of the developed method in the normal hematocrit ranges (eg, 29.0%-59.0%). DBS and plasma or venous concentrations were highly correlated (correlation coefficient, 0.872-0.999) for all drugs, except mitotane, which did not meet a predefined level of significance (r > 0.872; correlation coefficient, r = 0.87, P < 0.0001).
CONCLUSIONS
DBS provides an alternative sampling strategy for the TDM of many anticancer drugs. Further research is required to establish a standardized approach for sampling and processing DBS samples to allow future implementation.
Topics: Humans; Mitotane; Antineoplastic Agents; Everolimus; Neoplasms; Vemurafenib
PubMed: 36750444
DOI: 10.1097/FTD.0000000000001082 -
Seminars in Oncology 2020Patients with severe renal impairment or undergoing hemodialysis are usually excluded from clinical trials. Available data regarding safety and activity of systemic...
BACKGROUND
Patients with severe renal impairment or undergoing hemodialysis are usually excluded from clinical trials. Available data regarding safety and activity of systemic therapies (ST) in hemodialyzed patients are scarce.
METHODS
Clinical data were searched through PubMed database until April 2020 according to PRISMA criteria. Efficacy, safety and pharmacokinetic (PK) assessment of ST were reported.
RESULTS
Among 270 references, 56 reports were evaluated in full text: 41 were included for efficacy and 42 for safety analysis (sunitinib n = 68, bevacizumab n = 6, everolimus n = 28, temsirolimus n = 17, sorafenib n = 55, axitinib n = 13, pazopanib n = 13, nivolumab n = 18, cabozantinib n = 0, lenvatinib n = 0, and ipilimumab n = 0). Twelve of the reports included PK assessment among dialyzed patients. Hemodialysis did not seem to modify the expected efficacy and safety of each compound among patients undergoing hemodialysis. PK assessments were not modified in comparison with a population not undergoing dialysis.
CONCLUSION
Targeted and Immune therapies seem to be effective and can be used among patients undergoing hemodialysis. Due to frailty and comorbidities associated to chronic hemodialysis enhanced vigilance for these therapies within this specific population is recommended. Dedicated prospective clinical trials would definitely help to obtain data with a higher level of evidence.
Topics: Antineoplastic Agents; Carcinoma, Renal Cell; Female; Humans; Immunotherapy; Kidney Neoplasms; Male; Molecular Targeted Therapy; Renal Dialysis
PubMed: 32522380
DOI: 10.1053/j.seminoncol.2020.05.001