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MicroRNA expression profiling of peripheral blood samples predicts resistance to first-line sunitinib in advanced renal cell carcinoma patients.

ABSTRACT: Anti-angiogenic therapy benefits many patients with advanced renal cell carcinoma (RCC), but there is still a need for predictive markers that help in selecting the best therapy for individual patients. MicroRNAs (miRNAs) regulate cancer cell behavior and may be attractive biomarkers for prognosis and prediction of response. Forty-four patients with RCC were recruited into this observational prospective study conducted in nine Spanish institutions. Peripheral blood samples were taken before initiation of therapy and 14 days later in patients receiving first-line therapy with sunitinib for advanced RCC. miRNA expression in peripheral blood was assessed using microarrays and L2 boosting was applied to filtered miRNA expression data. Several models predicting poor and prolonged response to sunitinib were constructed and evaluated by binary logistic regression. Blood samples from 38 patients and 287 miRNAs were evaluated. Twenty-eight miRNAs of the 287 were related to poor response and 23 of the 287 were related to prolonged response to sunitinib treatment. Predictive models identified populations with differences in the established end points. In the poor response group, median time to progression was 3.5 months and the overall survival was 8.5, whereas in the prolonged response group these values were 24 and 29.5 months, respectively. Ontology analyses pointed out to cancer-related pathways, such angiogenesis and apoptosis. miRNA expression signatures, measured in peripheral blood, may stratify patients with advanced RCC according to their response to first-line therapy with sunitinib, improving diagnostic accuracy. After proper validation, these signatures could be used to tailor therapy in this setting.

SUBMITTER: Gamez-Pozo A

PROVIDER: S-EPMC3541518 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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MicroRNA expression profiling of peripheral blood samples predicts resistance to first-line sunitinib in advanced renal cell carcinoma patients.

Gámez-Pozo Angelo A Antón-Aparicio Luis M LM Bayona Cristina C Borrega Pablo P Gallegos Sancho María I MI García-Domínguez Rocío R de Portugal Teresa T Ramos-Vázquez Manuel M Pérez-Carrión Ramón R Bolós María V MV Madero Rosario R Sánchez-Navarro Iker I Fresno Vara Juan A JA Espinosa Arranz Enrique E

Neoplasia (New York, N.Y.) 20121201 12

Anti-angiogenic therapy benefits many patients with advanced renal cell carcinoma (RCC), but there is still a need for predictive markers that help in selecting the best therapy for individual patients. MicroRNAs (miRNAs) regulate cancer cell behavior and may be attractive biomarkers for prognosis and prediction of response. Forty-four patients with RCC were recruited into this observational prospective study conducted in nine Spanish institutions. Peripheral blood samples were taken before init ...[more]

PMID: 23308047

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Project description:BackgroundThe data from the phase III clinical trial KEYNOTE-426 indicated that pembrolizumab plus axitinib compared with sunitinib could generate clinical benefits in patients with previously untreated advanced renal cell carcinoma (RCC). Given the incremental clinical benefits, we examined the potential cost-effectiveness of pembrolizumab plus axitinib versus sunitinib in the first-line setting for patients with advanced RCC from the U.S. payers' perspective.Materials and methodsCost and health outcomes were estimated at a willingness-to-pay (WTP) threshold of $100,000 to $150,000 per quality-adjusted life-year (QALY). One-way and probabilistic sensitivity analyses were performed by varying potentially modifiable parameters, and additional subgroup analyses were performed as well.ResultsUpon our analyses, the total treatment costs in the pembrolizumab plus axitinib and sunitinib groups were $522,796 and $348,424 and the QALYs gained 2.90 and 1.72, respectively. In the base-case analysis, compared with receiving sunitinib, patients with advanced RCC receiving pembrolizumab plus axitinib gained 1.18 more QALYs at an incremental cost-effectiveness ratio of $148,676/QALY. The results of subgroup analyses demonstrated that pembrolizumab plus axitinib was most cost-effective for patients who had one organ with metastasis.ConclusionFirst-line treatment with pembrolizumab plus axitinib, compared with sunitinib, is a cost-effective strategy when the value of WTP is from $100,000 to $150,000 per QALY in patients with advanced RCC. For patients with one-organ metastasis and those in International Metastatic Renal Cell Carcinoma Database Consortium poor risk group, first-line treatment with pembrolizumab plus axitinib is more cost-effective than others.Implications for practiceThis was the first study to examine the cost-effectiveness of pembrolizumab plus axitinib versus sunitinib in advanced renal cell carcinoma (RCC). This study found that first-line treatment with pembrolizumab plus axitinib is a cost-effective strategy when the value of willingness-to-pay is from $100,000 to $150,000 per quality-adjusted life-year in patients with advanced RCC from the U.S. payers' perspective.

Project description:BackgroundCabozantinib Versus Sunitinib as Initial Targeted Therapy for Patients With Metastatic Renal Cell Carcinoma of Poor or Intermediate Risk: The Alliance A031203 CABOSUN Trial (CABOSUN) was a randomized, open-label, phase 2 trial evaluating first-line cabozantinib versus sunitinib in patients with advanced renal cell carcinoma (aRCC). This post hoc analysis evaluated quality-adjusted survival using Quality-adjusted Time Without Symptoms of disease or Toxicity of treatment (Q-TWiST).MethodsSurvival plots for cabozantinib and sunitinib (650-day follow-up) were partitioned into 3 health states: time spent before disease progression without toxicity (TWiST; toxicity based on National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0] grade 3/4 adverse events), time spent before disease progression with toxicity (TOX; durations of adverse events based on published literature), and time after disease recurrence (relapse) or progression to death (REL). Q-TWiST was the sum of the mean time spent in each state, with each state weighted to reflect patient preferences (from 0 [worst] to 1 [best]) using utility scores. TWiST was always weighted as 1. Overall survival and time to disease progression were based on all randomized patients (157 patients); TOX was based on all randomized and treated patients (150 patients).ResultsAcross all utility combinations tested, Q-TWiST was found to be longer with cabozantinib versus sunitinib (range of differences, +24 days to +137 days). Q-TWiST differences that were found to be statistically significant (+92 days [95% confidence interval, 5-178 days] to +137 days [95% confidence interval, 60-214 days]) were of a clinically meaningful effect size (?80 days), and were based on utility values that included those considered relevant for patients with aRCC (REL utility weight of 0.355, TOX utility weight of 0-1, and TWiST utility weight of 1).ConclusionsIn patients with aRCC, first-line cabozantinib was found to provide longer quality-adjusted survival compared with sunitinib. These findings may help to inform clinical decision making.Lay summaryCabozantinib and sunitinib are drugs that are used to treat patients with advanced kidney cancer. Clinical trials have shown that cabozantinib offers benefits over sunitinib, giving patients more time before their cancer progresses. It is important that this additional time before disease progression does not come at the expense of patients' quality of life, which can be affected by treatment side effects and/or ongoing cancer symptoms. Both quantity and quality of life are central to optimal treatment. In the current analysis of patients with advanced kidney cancer who were initiating treatment for the first time, cabozantinib provided more quality time before cancer progression compared with sunitinib.

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MicroRNA expression profiling of peripheral blood samples predicts resistance to first-line sunitinib in advanced renal cell carcinoma patients.

Publications

MicroRNA expression profiling of peripheral blood samples predicts resistance to first-line sunitinib in advanced renal cell carcinoma patients.

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