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Comparative efficacy and safety of axitinib versus sorafenib in metastatic renal cell carcinoma: a systematic review and meta-analysis.

ABSTRACT: OBJECTIVE:This study was performed to evaluate the comparative efficacy and safety of axitinib and sorafenib in the therapy of metastatic renal cell carcinoma. MATERIALS AND METHODS:Eligible studies were searched from PubMed, Embase, and Future Medicine databases. The pooled hazard ratios and relative risk ratios (RRs) were calculated by using Stata 12.0 software. RESULTS:A total of 1,011 patients qualified to participate in this Phase III study that included randomized controlled trials. Meta-analysis results showed that axitinib was more highly and significantly associated with a survival benefit in the independently assessed progression-free survival in comparison to sorafenib. The values of RR of the objective response rate and disease control rate were also significantly different. Results of the analysis of adverse events concerning hypertension and hypothyroidism demonstrated that the values of RR were significantly higher in the axitinib group and lower risks were established in the patients treated with axitinib. CONCLUSION:Therefore, axitinib was a better treatment option for metastatic renal cell carcinoma treatment than sorafenib, especially after failure of prior systemic therapies. This analysis revealed that axitinib had higher risks of hypertension and hypothyroidism and lower risks of rash and palmar-plantar erythrodysesthesia.

SUBMITTER: Wang H

PROVIDER: S-EPMC4907737 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Comparative efficacy and safety of axitinib versus sorafenib in metastatic renal cell carcinoma: a systematic review and meta-analysis.

Wang Hai H Man Libo L Li Guizhong G Huang Guanglin G Wang Jianwei J

OncoTargets and therapy 20160608

<h4>Objective</h4>This study was performed to evaluate the comparative efficacy and safety of axitinib and sorafenib in the therapy of metastatic renal cell carcinoma.<h4>Materials and methods</h4>Eligible studies were searched from PubMed, Embase, and Future Medicine databases. The pooled hazard ratios and relative risk ratios (RRs) were calculated by using Stata 12.0 software.<h4>Results</h4>A total of 1,011 patients qualified to participate in this Phase III study that included randomized con ...[more]

PMID: 27354814

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Project description:Purpose: Sorafenib and sunitinib are extensively used as first-line medications for metastatic renal cell carcinoma (mRCC). This meta-analysis was conducted to assess the antitumor efficacy, toxicity, and costs of the two drugs among mRCC patients. Materials and methods: PubMed, ScienceDirect, Scopus, Web of Science, Ovid MEDLINE, the Cochrane Library, Embase, and Google Scholar were searched for eligible articles. The endpoints consisted of progression-free survival (PFS), overall survival (OS), objective response rate (ORR), adverse effects (AEs), and per-patient-per-month (PPPM) costs. Results: We included 14 studies with 2,925 patients. Both drugs were valid for treating mRCC with equivalent PFS [hazard ratio (HR) = 0.98, 95% confidence interval (CI): 0.88-1.10, P = 0.74] and disease control rates [DCRs; risk ratio (RR) = 1.03, 95% CI: 0.98-1.08, P = 0.28], but sunitinib had a better OS (HR = 1.10, 95% CI: 1.01-1.20, P = 0.04) and higher ORR (HR = 0.66, 95% CI: 0.45-0.97, P = 0.03) than sorafenib. Furthermore, sunitinib induced more incidences of severe hematologic AEs (anemia, neutropenia, and thrombocytopenia) and stomatitis/mucositis than sorafenib. In the subanalysis, Asian patients treated with sorafenib reported a longer PFS than those treated with sunitinib (HR = 0.87, 95% CI: 0.83-0.90, P = 0.01), and European patients treated with sunitinib had a longer OS than those treated with sorafenib (HR = 1.17, 95% CI: 1.01-1.30, P = 0.04). Moreover, the pooled results of the high-quality studies reported a higher ORR with sunitinib than with sorafenib, and medium-quality studies showed a longer OS with sunitinib than with sorafenib. Conclusions: Sunitinib has more benefits (longer OS and better ORR) than sorafenib as a first-line therapy for mRCC. However, sunitinib has higher toxicity than sorafenib. Sorafenib might be more suitable than sunitinib among Asian patients, and sunitinib might be superior to sorafenib in European patients. Nevertheless, more large-scale, high-quality studies are required.

Project description:In recent years, targeted agents have changed the treatment landscape for patients with advanced renal cell carcinoma (RCC), greatly improving treatment outcomes. Several targeted agents are now licensed for the treatment of metastatic RCC (mRCC), and a number of new agents are under investigation. Axitinib, a small molecule indazole derivative is an oral, potent multitargeted tyrosine kinase receptor inhibitor, which selectively inhibits vascular endothelial growth factor receptors (VEGFR)-1, -2, and -3 at subnanomolar concentrations, in vitro. In various nonclinical models, axitinib has demonstrated in vivo target modulation and antiangiogenesis. In pharmacokinetic studies, axitinib administered orally with food at the proposed regimen of 5?mg twice daily continuous daily dosing, is rapidly absorbed, reaching peak concentrations within 2-6 hours. Axitinib is metabolized primarily in the liver via the cytochrome P450 (CYP) system with less than 1% of the administered drug passing unchanged in the urine. The pharmacokinetics of axitinib do not appear to be altered by coadministered chemotherapies, and antacids do not have a clinically significant effect. However, coadministration with CYP3A4 and 1A2 inducers is contraindicated. In addition, proton pump inhibitors reduce the rate of axitinib absorption. Increased axitinib exposure is associated with higher efficacy indicated by decreased tumor perfusion and volume. In three phase II clinical trials in patients with advanced RCC previously treated with cytokines, chemotherapy or targeted agents, axitinib has demonstrated antitumor activity with a favorable non-cumulative toxicity profile. In one study of Western patients with cytokine-refractory mRCC, an objective response rate (ORR) of 44.2% (95% CI 30.5, 58.7) was achieved. The median time to progression was 15.7 months (95% CI 8.4, 23.4) and the median overall survival (OS) was 29.9 months (95% CI 20.3, not estimable). In the second study of patients with sorafenib-refractory mRCC, ORR was 22.6% (95% CI 12.9, 35.0). The median progression-free survival (PFS) was 7.4 months (95% CI 6.7, 11.0) and a median OS of 13.6 months (95% CI 8.4, 18.8) was achieved. Results from the third study in Japanese patients with cytokine-refractory mRCC reported an ORR of 55% and median PFS of 12.9 months (95% CI 9.8, 15.6). In the three studies, the most common adverse events reported were fatigue, hypertension, hand-foot syndrome (HFS), and gastrointestinal toxicity, which were generally manageable with standard medical intervention. Of note, the incidence of HFS and proteinuria in the Japanese study was higher than that reported in the Western study in cytokine-refractory mRCC patients. An observed association between diastolic blood pressure ?90?mmHg and increased efficacy suggests potential use as a prognostic biomarker. However, this requires further investigation. Two randomized phase III clinical trials are ongoing to determine the efficacy of axitinib in patients with mRCC in the first- and second-line setting. These results will help to determine the place of axitinib in the mRCC treatment algorithm.

Dataset Information

Comparative efficacy and safety of axitinib versus sorafenib in metastatic renal cell carcinoma: a systematic review and meta-analysis.

Publications

Comparative efficacy and safety of axitinib versus sorafenib in metastatic renal cell carcinoma: a systematic review and meta-analysis.

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