Comparison of efficacy and safety among axitinib, sunitinib, and sorafenib as neoadjuvant therapy for renal cell carcinoma: a retrospective study.
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ABSTRACT:
SUBMITTER: Cai W
PROVIDER: S-EPMC6788019 | biostudies-literature | 2019 Oct
REPOSITORIES: biostudies-literature
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Comparison of efficacy and safety among axitinib, sunitinib, and sorafenib as neoadjuvant therapy for renal cell carcinoma: a retrospective study.
Cai Wen W Cai Biao B Zhou Juan J Chen Yonghui Y Zhang Jin J Huang Yiran Y Xue Wei W Huang Jiwei J
Cancer communications (London, England) 20191011 1
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Project description:This paper reviews current treatments for renal cell carcinoma/cancer (RCC) with the multikinase inhibitors (MKIs) sorafenib, sunitinib, lenvatinib and axitinib. Furthermore, it compares these drugs regarding progression-free survival, overall survival and adverse effects (AE), with a focus on hypertension. Sorafenib and sunitinib, which are included in international clinical guidelines as first- and second-line therapy in metastatic RCC, are now being challenged by new-generation drugs like lenvatinib and axitinib. These drugs have shown significant clinical benefits for patients with RCC, but all four induce a variety of AEs. Hypertension is one of the most common AEs related to MKI treatment. Comparing sorafenib, sunitinib and lenvatinib revealed that sorafenib and sunitinib had the same efficacy, but sorafenib was safer to use. Lenvatinib showed better efficacy than sorafenib but worse safety. No trials have yet been completed that compare lenvatinib with sunitinib. Although axitinib promotes slightly higher hypertension rates compared to sunitinib, the overall discontinuation rate and cardiovascular complications are favourable. Although the mean rate of patients who develop hypertension is similar for each drug, some trials have shown large differences, which could indicate that lifestyle and/or genetic factors play an additional role.
| S-EPMC6801695 | biostudies-literature
Project description:ObjectiveThis study was performed to evaluate the comparative efficacy and safety of axitinib and sorafenib in the therapy of metastatic renal cell carcinoma.Materials and methodsEligible 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.ResultsA 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.ConclusionTherefore, 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.
| S-EPMC4907737 | biostudies-literature
Project description:To evaluate the safety and efficiency of sunitinib and sorafenib in the treatment of renal cell carcinoma (RCC).Databases were searched up till February 28, 2018. Two reviewers independently assessed trials for eligibility, quality, and extracted relevant data. Results are expressed as risk ratio (RR) or hazard ratio (HR) with 95% confidence intervals (CI). Six studies including 3112 patients were accessed. Sorafenib group exhibited higher median progression-free survival (mPFS) compared to sunitinib group (MD, -1.30; 95% CI, -2.56 to -0.03), especially in the first-line treatment (MD, -1.33; 95% CI, -2.61 to -0.04). However, sunitinib significantly reduced the risk of progression-free survival (PFS) compared to sorafenib (HR, 0.71; 95% CI, 0.6-0.82). Sunitinib also significantly reduced risk of overall survival (OS) compared to sorafenib (HR, 0.79; 95% CI, 0.65-0.92), while median OS was similar in both groups (MD, -0.48; 95% CI, -3.40-2.43). With regards to safety, the risk of rash (RR, 0.31, 95% CI, 0.12-0.79) was greater in sunitinib than sorafenib group, while the risk of decreased appetite (RR 2.10, 95% CI: 1.33-3.30) and dehydration (RR 2.73, 95% CI: 1.14-6.56) was smaller in contrast.Based on risk of PFS and OS, sunitinib was a better treatment option for RCC treatment while patients faced with severe skin reaction. And for those Asian patients classified under MSKCC moderate risk, whether in first or second-line treatment, had difficulty in feeding, sorafenib is a better choice for prolong mPFS.
| S-EPMC7220148 | biostudies-literature
Project description:Sorafenib and sunitinib are widely used as first-line targeted therapy for metastatic renal cell carcinoma (mRCC) in China. This study aimed to compare the efficacy, safety, and quality of life (QoL) in Chinese mRCC patients treated with sorafenib and sunitinib as first-line therapy.Clinical data of patients with mRCC who received sorafenib (400 mg twice daily; 4 weeks) or sunitinib (50 mg twice daily; on a schedule of 4 weeks on treatment followed by 2 weeks off) were retrieved. Primary outcomes were overall survival (OS), progression-free survival (PFS), adverse events (AEs), and QoL (SF-36 scores), and secondary outcomes were associations of clinical characteristics with QoL.Medical records of 184 patients (110 in the sorafenib group and 74 in the sunitinib group) were reviewed. PFS and OS were comparable between the sorafenib and sunitinib groups (both P > 0.05). The occurrence rates of leukocytopenia, thrombocytopenia, and hypothyroidism were higher in the sunitinib group (36.5% vs. 10.9%, P < 0.001; 40.5% vs. 10.9%, P < 0.001; 17.6% vs. 3.6%, P = 0.001), and that of diarrhea was higher in the sorafenib group (62.7% vs. 35.2%, P < 0.001). There was no significant difference in SF-36 scores between the two groups. Multivariate analysis indicated that role-physical and bodily pain scores were associated with the occurrence rate of grade 3 or 4 AEs (P = 0.017 and 0.005).Sorafenib has comparable efficacy and lower toxicity profile than sunitinib as first-line therapy for mRCC. Both agents showed no significant impact on QoL of patients.
| S-EPMC5547674 | biostudies-other
Project description:BackgroundIn a single-group, phase 1b trial, avelumab plus axitinib resulted in objective responses in patients with advanced renal-cell carcinoma. This phase 3 trial involving previously untreated patients with advanced renal-cell carcinoma compared avelumab plus axitinib with the standard-of-care sunitinib.MethodsWe randomly assigned patients in a 1:1 ratio to receive avelumab (10 mg per kilogram of body weight) intravenously every 2 weeks plus axitinib (5 mg) orally twice daily or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle). The two independent primary end points were progression-free survival and overall survival among patients with programmed death ligand 1 (PD-L1)-positive tumors. A key secondary end point was progression-free survival in the overall population; other end points included objective response and safety.ResultsA total of 886 patients were assigned to receive avelumab plus axitinib (442 patients) or sunitinib (444 patients). Among the 560 patients with PD-L1-positive tumors (63.2%), the median progression-free survival was 13.8 months with avelumab plus axitinib, as compared with 7.2 months with sunitinib (hazard ratio for disease progression or death, 0.61; 95% confidence interval [CI], 0.47 to 0.79; P<0.001); in the overall population, the median progression-free survival was 13.8 months, as compared with 8.4 months (hazard ratio, 0.69; 95% CI, 0.56 to 0.84; P<0.001). Among the patients with PD-L1-positive tumors, the objective response rate was 55.2% with avelumab plus axitinib and 25.5% with sunitinib; at a median follow-up for overall survival of 11.6 months and 10.7 months in the two groups, 37 patients and 44 patients had died, respectively. Adverse events during treatment occurred in 99.5% of patients in the avelumab-plus-axitinib group and in 99.3% of patients in the sunitinib group; these events were grade 3 or higher in 71.2% and 71.5% of the patients in the respective groups.ConclusionsProgression-free survival was significantly longer with avelumab plus axitinib than with sunitinib among patients who received these agents as first-line treatment for advanced renal-cell carcinoma. (Funded by Pfizer and Merck [Darmstadt, Germany]; JAVELIN Renal 101 ClinicalTrials.gov number, NCT02684006.).
| S-EPMC6716603 | biostudies-literature
Project description: Not available
| S-EPMC8798318 | biostudies-literature
Project description:BackgroundWe retrospectively analyzed sunitinib outcome as a function of age in metastatic renal cell carcinoma (mRCC) patients.MethodsData were pooled from 1059 patients in six trials. Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS) were compared by log-rank test between patients aged <70 (n=857; 81%) and ≥70 (n=202; 19%) years.ResultsIn first-line patients, median PFS was comparable in younger and older patients, 9.9 vs 11.0 months, respectively (HR, 0.89; 95% CI: 0.73-1.09; P=0.2629), as was median OS, 23.6 vs 25.6 months (HR, 0.93; 95% CI: 0.74-1.18; P=0.5442). Similarly, in cytokine-refractory patients, median PFS was 8.1 vs 8.4 months (HR, 0.79; 95% CI: 0.49-1.28; P=0.3350), while median OS was 20.2 vs 15.8 months (HR, 1.14; 95% CI: 0.73-1.79; P=0.5657). Some treatment-emergent adverse events were significantly less common in younger vs older patients, including fatigue (60% vs 69%), cough (20% vs 29%), peripheral edema (17% vs 27%), anemia (18% vs 25%), decreased appetite (13% vs 29%), and thrombocytopenia (16% vs 25%; all P<0.05). Hand-foot syndrome was more common in younger patients (32% vs 24%).ConclusionsAdvanced age should not be a deterrent to sunitinib therapy and elderly patients may achieve additional clinical benefit.
| S-EPMC3950861 | biostudies-literature
Project description:ObjectiveAxitinib is a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors 1, 2 and 3. The efficacy and safety of axitinib in Japanese patients with metastatic renal cell carcinoma were evaluated.MethodsA subgroup analysis was conducted in Japanese patients enrolled in the randomized Phase III trial of axitinib versus sorafenib after failure of one prior systemic therapy for metastatic renal cell carcinoma.ResultsTwenty-five (of 361) and 29 (of 362) patients randomized to the axitinib and sorafenib arms, respectively, were Japanese and included in this analysis. Median progression-free survival in Japanese patients was 12.1 months (95% confidence interval 8.6 to not estimable) for axitinib and 4.9 months (95% confidence interval 2.8-6.6) for sorafenib (hazard ratio 0.390; 95% confidence interval 0.130-1.173; stratified one-sided P = 0.0401). The objective response rate was 52.0% for axitinib and 3.4% for sorafenib (P = 0.0001). The common all-causality adverse events (all grades) in Japanese patients were dysphonia (68%), hypertension (64%), hand-foot syndrome (64%) and diarrhea (56%) for axitinib, and hand-foot syndrome (86%), hypertension (62%) and diarrhea (52%) for sorafenib. The safety profiles of axitinib and sorafenib in Japanese patients were generally similar to those observed in the overall population, with the exceptions of higher incidences of hypertension, dysphonia, hand-foot syndrome, hypothyroidism and stomatitis.ConclusionsAxitinib is efficacious and well tolerated in Japanese patients with previously treated metastatic renal cell carcinoma, consistent with the results in the overall population, providing a new targeted therapy for these Japanese patients.
| S-EPMC3664320 | biostudies-literature
Project description:The relationships between exposure, biomarkers (vascular endothelial growth factor (VEGF), soluble VEGF receptors (sVEGFR)-1, -2, -3, and soluble stem cell factor receptor (sKIT)), tumor sum of longest diameters (SLD), diastolic blood pressure (dBP), and overall survival (OS) were investigated in a modeling framework. The dataset included 64 metastatic renal cell carcinoma patients (mRCC) treated with oral axitinib. Biomarker timecourses were described by indirect response (IDR) models where axitinib inhibits sVEGFR-1, -2, and -3 production, and VEGF degradation. No effect was identified on sKIT. A tumor model using sVEGFR-3 dynamics as driver predicted SLD data well. An IDR model, with axitinib exposure stimulating the response, characterized dBP increase. In a time-to-event model the SLD timecourse predicted OS better than exposure, biomarker- or dBP-related metrics. This type of framework can be used to relate pharmacokinetics, efficacy, and safety to long-term clinical outcome in mRCC patients treated with VEGFR inhibitors. (ClinicalTrial.gov identifier NCT00569946.).
| S-EPMC5488123 | biostudies-literature
Project description:BackgroundThe phase 3 JAVELIN Renal 101 trial (NCT02684006) demonstrated significantly improved progression-free survival (PFS) with first-line avelumab plus axitinib versus sunitinib in advanced renal cell carcinoma (aRCC). We report updated efficacy data from the second interim analysis.Patients and methodsTreatment-naive patients with aRCC were randomized (1 : 1) to receive avelumab (10 mg/kg) intravenously every 2 weeks plus axitinib (5 mg) orally twice daily or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle). The two independent primary end points were PFS and overall survival (OS) among patients with programmed death ligand 1-positive (PD-L1+) tumors. Key secondary end points were OS and PFS in the overall population.ResultsOf 886 patients, 442 were randomized to the avelumab plus axitinib arm and 444 to the sunitinib arm; 270 and 290 had PD-L1+ tumors, respectively. After a minimum follow-up of 13 months (data cut-off 28 January 2019), PFS was significantly longer in the avelumab plus axitinib arm than in the sunitinib arm {PD-L1+ population: hazard ratio (HR) 0.62 [95% confidence interval (CI) 0.490-0.777]}; one-sided P < 0.0001; median 13.8 (95% CI 10.1-20.7) versus 7.0 months (95% CI 5.7-9.6); overall population: HR 0.69 (95% CI 0.574-0.825); one-sided P < 0.0001; median 13.3 (95% CI 11.1-15.3) versus 8.0 months (95% CI 6.7-9.8)]. OS data were immature [PD-L1+ population: HR 0.828 (95% CI 0.596-1.151); one-sided P = 0.1301; overall population: HR 0.796 (95% CI 0.616-1.027); one-sided P = 0.0392].ConclusionAmong patients with previously untreated aRCC, treatment with avelumab plus axitinib continued to result in a statistically significant improvement in PFS versus sunitinib; OS data were still immature.Clinical trial numberNCT02684006.
| S-EPMC8436592 | biostudies-literature