New approaches to first-line treatment of advanced renal cell carcinoma.
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ABSTRACT:
SUBMITTER: George DJ
PROVIDER: S-EPMC8435931 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Renal cell carcinoma (RCC) is among the 10 most common cancers in the USA. One-third of the patients diagnosed with this cancer present with locally advanced or metastatic disease. In the past, advanced disease conferred poor survival outcomes; however, the treatment paradigm for RCC has been revolutionized twice since 2005. The initial wave of revolution came with the emergence of vascular endothelial growth factor (VEGF) inhibitors and a second wave arose more recently with the emergence and unprecedented success of checkpoint inhibitors in RCC. A third wave combining these two strategies is well underway and likely represents the new paradigm to improve survival outcomes for afflicted patients. In this review, we discuss the current treatment landscape for patients with advanced RCC, focusing on approved VEGF and checkpoint inhibitors in the first-line setting as well as highlighting landmark combination clinical trials.
| S-EPMC7231754 | biostudies-literature
Project description:BackgroundIn this study, compared to sunitinib as one of the available treatment options, we aimed to evaluate the cost-effectiveness of lenvatinib plus pembrolizumab or everolimus as first-line treatment for advanced renal cell carcinoma (RCC) patients in a Chinese health system setting.MethodsA partitioned survival model was developed to simulate patient disease and death. Transition probabilities and adverse reaction data were obtained from the CLEAR trial. The utility value was derived from literature. Costs were based on the Chinese drug database and local charges. Sensitivity analyses and were performed to assess the robustness of the model. Outcomes were measured as quality-adjusted life-years (QALYs), cumulative cost (COST), and incremental cost-effectiveness ratio (ICER).ResultsThe model predicted that the expected mean result in the lenvatinib plus pembrolizumab group (2.60 QALYs) was superior to that in the sunitinib group (2.13 QALYs) to obtain 0.47 QALYs, but the corresponding cost was 1,253,130 yuan greater, resulting in an ICER of 2,657,025 RMB/QALYs. Compared with the sunitinib group, the lenvatinib plus everolimus group (2.17 QALYs) gained 0.04 QALYs, with an additional cost of 32,851 yuan, resulting in an ICER of 77,6202 RMB/QALYs.ConclusionsLenvatinib plus pembrolizumab or everolimus has no economic advantage over sunitinib in treating advanced RCC in the Chinese healthcare system.
| S-EPMC9254865 | biostudies-literature
Project description:BACKGROUND:Thymic carcinomas (TCs) are rare aggressive tumors with no standard first-line treatment. This study was conducted to determine the optimal chemotherapy regimen for advanced TC. METHODS:This retrospective study included 67 patients treated for stage IV TC in 2006-2015. The primary endpoints were the objective response rate (ORR) and progression-free survival (PFS) with different chemotherapy regimens. Multivariate Cox regression analysis was used to identify factors associated with PFS, including metastatic status, radiotherapy post-chemotherapy, primary lesion resection before chemotherapy, and chemotherapy regimen. RESULTS:A total of 36 patients received a paclitaxel-platinum regimen, 31 received a gemcitabine-platinum regimen, 14 underwent primary lesion resection, and 33 underwent radiotherapy. ORR was 31% (11/36) and 29% (9/31) in the paclitaxel-platinum and gemcitabine-platinum groups, respectively (P = 0.890). Median PFS, one-year PFS rate, and two-year PFS rate were 7.0 months, 26%, and 6% with paclitaxel-platinum treatment and 12 months, 48%, and 24% with gemcitabine-platinum treatment (log-rank P = 0.030). Median PFS, one-year PFS rate, and two-year PFS rate were 18.0 months, 57%, and 33% with surgical resection and 7.3 months, 31%, and 7% without resection (log-rank P = 0.030). Median PFS, one-year PFS rate, and two-year PFS rate were 13.0 months, 52%, and 20% with radiotherapy and 4.3 months, 22%, and 7% without radiotherapy (log-rank P = 0.001). In multivariate analysis, metastatic status (hazard ratio [HR], 0.33, P = 0.004), surgical resection (HR, 0.32; P = 0.004), and radiotherapy (HR, 0.32; P < 0.001) were associated with superior PFS. CONCLUSIONS:Both gemcitabine-platinum and paclitaxel-platinum regimens were efficacious for advanced TC. Primary lesion resection and radiotherapy may also benefit selected patients.
| S-EPMC6825903 | biostudies-other
Project description:Agents targeting the vascular endothelial growth factor (VEGF) and its receptors (VEGFRs), as well as the mammalian target of rapamycin (mTOR) and immune checkpoint receptor programmed death 1 (PD-1) signaling pathway have improved clinical outcomes for patients with advanced renal cell carcinoma (RCC). The VEGFR tyrosine kinase inhibitors (TKIs) pazopanib and sunitinib are FDA-approved first-line treatment options for advanced RCC; however, other treatment options in this setting are available, including the recently approved combination of nivolumab (anti-PD-1) and ipilimumab (anti-cytotoxic T-lymphocyte-associated protein-4 [CTLA-4]) for patients with intermediate or poor risk. Unfortunately, treatment guideline recommendations provide little guidance to aid first-line treatment choice. In addition, several ongoing randomized phase III trials of investigational first-line regimens may complicate the RCC treatment paradigm if these agents gain approval. This article reviews clinical trial and real-world evidence for currently approved and investigational first-line treatment regimens for advanced RCC and provides clinical evidence to aid first-line treatment selection. IMPLICATIONS FOR PRACTICE: Vascular endothelial growth factor receptor tyrosine kinase inhibitors are approved by the U.S. Food and Drug Administration as first-line treatment options for advanced renal cell carcinoma; however, the treatment paradigm is rapidly evolving. The combination of nivolumab plus ipilimumab was recently approved for intermediate- and poor-risk patients, and other combination strategies and novel first-line agents will likely be introduced soon.
| S-EPMC6519762 | biostudies-literature
Project description:Recent data from the COMPARZ study seem to suggest a non-inferiority of pazopanib confronted with sunitinib in PFS and OS. We previously reported how VEGF and VEGFR polymorphisms might have a predictive role in patients treated with first-line sunitinib. Aim of our study was to investigate whether tumour angiogenesis genotyping could influence clinical outcome in RCC patients treated with either sunitinib or pazopanib, in order to help clinicians select the appropriate treatment for each patient.19 patients were treated with pazopanib while 78 received sunitinib. VEGF A rs833061 resulted significant in PFS in sunitinib vs pazopanib patients (CC+CT>TT in sunitinib, TT>CC+CT in pazopanib; p<0,0001); VEGF A rs2010963 resulted significant in PFS in sunitinib vs pazopanib patients (GG+CG>CC in sunitinib, CC>GG+CG in pazopanib; p<0,0001); VEGF A rs699947 resulted significant in PFS in sunitinib vs pazopanib patients (AA+AC>CC in sunitinib, CC>AA+AC in pazopanib; p<0,0001). OS showed no statistically significant difference.in our analysis patients with opposite polymorphisms of rs833061, rs2010963, rs699947 of VEGF A seems to have a better PFS if treated with either sunitinib or pazopanib. Our data seem to suggest that biology could have a role choosing first line treatment for mRCC patients.a retrospective analysis on 97 histologic samples of mRCC patients was conducted for VEGF-A, VEGF-C and VEGFR-1,2,3 single nucleotide polymorphisms (SNPs).
| S-EPMC5122335 | biostudies-literature
Project description:BACKGROUND:Nivolumab plus ipilimumab improves overall survival and is associated with less toxicity compared with sunitinib in the first-line setting of advanced renal-cell carcinoma (RCC). The current study aimed to assess the cost-effectiveness of nivolumab plus ipilimumab for first-line treatment of advanced RCC from the payer perspectives high- and middle-income regions. METHODS:A decision-analytic model was constructed to evaluate the health and economic outcomes of first-line sunitinib and nivolumab plus ipilimumab treatment associated with advanced RCC. The clinical and utility data were obtained from published reports. The cost data were acquired for the payer perspectives of the United States (US), United Kingdom (UK), and China. Sensitivity analyses were performed to test the uncertainties of the results. Quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) were used. RESULTS:Nivolumab plus ipilimumab gained 0.70-0.76 QALYs compared with sunitinib. Our analysis determined the following ICERs for nivolumab plus ipilimumab over sunitinib in first-line advanced RCC treatment: US $ 85,506 /QALY; UK $ 126,499/QALY; and China $ 4682/QALY. Sensitivity analyses found the model outputs to be most affected for body weight and for the prices of nivolumab, sunitinib and ipilimumab. CONCLUSIONS:Nivolumab plus ipilimumab as first-line treatment could gain more health benefits for advanced RCC in comparison with standard sunitinib, which is considered to be cost-effective in the US and China but not in the UK.
| S-EPMC6247499 | biostudies-literature
Project description:Everolimus is an oral inhibitor of mammalian target of rapamycin (mTOR-I) and is currently approved for the treatment of metastatic renal cell carcinoma (mRCC) after failure of first-line vascular endothelial growth factor receptor tyrosine kinase inhibitor (TKI). In this narrative review, we aim to report the available evidence about the use of everolimus as second-line therapy for mRCC. A literature search was performed using PubMed/MEDLINE and abstracts from major conferences on clinical oncology as sources. We report data from prospective as well as retrospective and real world data studies and we analyze the safety and efficacy profile of everolimus as second-line therapy for mRCC. Although different drugs are currently available for the second-line treatment of mRCC, everolimus represents a feasible and safe option in this setting, especially for patients who have experienced high-grade toxicity or are still carrying TKI-related toxicities from first-line treatment.
| S-EPMC4549702 | biostudies-literature
Project description:PurposePatients with advanced renal cell carcinoma with sarcomatoid features (sRCC) have poor prognoses and suboptimal outcomes with targeted therapy. This post hoc analysis of the phase III CheckMate 214 trial analyzed the efficacy of nivolumab plus ipilimumab (NIVO+IPI) versus sunitinib in patients with sRCC.Patients and methodsPatients with sRCC were identified via independent central pathology review of archival tumor tissue or histologic classification per local pathology report. Patients were randomized 1:1 to receive nivolumab (3 mg/kg) plus ipilimumab (1 mg/kg) every 3 weeks (four doses) then nivolumab 3 mg/kg every 2 weeks, or sunitinib 50 mg orally every day (4 weeks; 6-week cycles). Outcomes in patients with sRCC were not prespecified. Endpoints in patients with sRCC and International Metastatic Renal Cell Carcinoma Database Consortium intermediate/poor-risk disease included overall survival (OS), progression-free survival (PFS) per independent radiology review, and objective response rate (ORR) per RECIST v1.1. Safety outcomes used descriptive statistics.ResultsOf 1,096 randomized patients in CheckMate 214, 139 patients with sRCC and intermediate/poor-risk disease and six with favorable-risk disease were identified. With 42 months' minimum follow-up in patients with sRCC and intermediate/poor-risk disease, median OS [95% confidence interval (CI)] favored NIVO+IPI [not reached (NR) (25.2-not estimable [NE]); n = 74] versus sunitinib [14.2 months (9.3-22.9); n = 65; HR, 0.45 (95% CI, 0.3-0.7; P = 0.0004)]; PFS benefits with NIVO+IPI were similarly observed [median 26.5 vs. 5.1 months; HR, 0.54 (95% CI, 0.33-0.86; P = 0.0093)]. Confirmed ORR was 60.8% with NIVO+IPI versus 23.1% with sunitinib, with complete response rates of 18.9% versus 3.1%, respectively. No new safety signals emerged.ConclusionsNIVO+IPI showed unprecedented long-term survival, response, and complete response benefits versus sunitinib in previously untreated patients with sRCC and intermediate/poor-risk disease, supporting the use of first-line NIVO+IPI for this population.See related commentary by Hwang et al., p. 5.
| S-EPMC8589223 | biostudies-literature
Project description:Background:Compared with the standard of care with sunitinib, avelumab plus axitinib can increase progression-free survival in the first-line of advanced renal cell carcinoma (RCC), but the economic effect of the treatment is unknown. The purpose of the research was to evaluate the cost-effectiveness of the avelumab plus axitinib versus sunitinib in first-line treatment for advanced RCC from the US payer perspective. Methods:A Markov model was developed to evaluate the economic and health outcomes of avelumab plus axitinib vs sunitinib in the first-line setting for advanced RCC. The clinical data were obtained from the JAVELIN Renal 101 Clinical Trials. Deterministic and probabilistic sensitivity analyses were performed to assess uncertainty in the model. Health outcomes were measured in quality-adjusted life-years (QALYs). Results:The incremental cost-effectiveness ratio (ICER) of avelumab plus axitinib compared with sunitinib was $565,232 per QALY, the costs were $884,626 and $669,838, QALYs were 3.67 and 3.29, respectively. Sensitivity analysis demonstrated that differences in utilities in PFS and after progression were the most influential factors within the model. When avelumab was at 30% of the full price or axitinib was at 40% of the full price, avelumab and axitinib were approved to be cost-effective if the WTP threshold was $150,000 per QALY. The subgroup analysis showed the ICER of avelumab plus axitinib compared with sunitinib for the patients with PD-L1-positive tumors was $588,105. Conclusion:Avelumab plus axitinib in the first-line treatment was not cost-effective in comparison with sunitinib when the threshold of willingness to pay (WTP) was $150,000 per QALY.
| S-EPMC7225300 | biostudies-literature
Project description:BACKGROUND:Non-clear cell (ncc) metastatic renal-cell carcinoma (RCC) has dismal results with standard systemic therapies and a generally worse prognosis when compared to its clear-cell counterpart. New systemic combination therapies have emerged for metastatic RCC (mRCC), but the pivotal phase III trials excluded patients with nccRCC, which constitute about 30% of metastatic RCC cases. AIM:To provide a piece of real-life evidence on the use of pazopanib in this patient subgroup. METHODS:The present study is a multicenter retrospective observational analysis aiming to assess the activity, efficacy, and safety of pazopanib as first-line therapy for advanced nccRCC patients treated in a real-life setting. RESULTS:Overall, 48 patients were included. At the median follow-up of 40.6 mo, the objective response rate was 27.1%, the disease control rate was 83.3%, and the median progression-free survival and overall survival were 12.3 (95% confidence interval [CI]: 3.6-20.9) and 27.7 (95%CI: 18.2-37.1) mo, respectively. Grade 3 adverse events occurred in 20% of patients, and no grade 4 or 5 toxicities were found. CONCLUSION:Pazopanib should be considered as a good first-line option for metastatic RCC with variant histology.
| S-EPMC8641010 | biostudies-literature