Dataset Information

Sorafenib as a second-line treatment in metastatic renal cell carcinoma in Mexico: a prospective cohort study.

ABSTRACT:

Background

Sequential inhibition of the vascular endothelial growth factor (VEGF) pathway with sorafenib could be useful for patients with metastatic renal cell carcinoma (RCC). Our aim was to determine the activity and tolerability of sorafenib as a second-line therapy in advanced RCC initially treated with a different VEGF-tyrosine kinase inhibitor (TKI).

Methods

A prospective observational cohort in Mexico (2012-2019). We included 132 subjects with metastatic RCC and who had progression despite treatment with sunitinib. The primary end-point was time to disease progression as evaluated every 12-16?weeks.

Results

The mean age of the cohort was 59?years (interquartile range [IQR] 50-72), 96 (73%) were men, and 48 (36%) had a favorable prognosis according to the IMDC (International Metastatic RCC Database Consortium) prognostic model. The median progression-free survival (PFS) and overall-survival after the introduction of sorafenib treatment was 8.6?months (95% confidence interval [CI]: 6.7-10.5) and 40?months (95% CI: 34.5-45.4) respectively. The median overall survival from RCC diagnosis to death was 71?months (95% CI: 58.2-83.8). On multivariable analyses, age?>?65?years was associated with a longer PFS (HR 0.51; 95% CI: 0.31-0.86; p?=?0.018). The median PFS in subjects aged >?65?years was longer compared to subjects ?65?years (14.0 [95% CI: 9.2-18.8] vs. 7.2?months [95% CI: 5.3-9.1]; p?=?0.012). Adverse events grade???3 associated with sorafenib occurred in 38 (29%) patients.

Conclusion

Sequential inhibition of VEGF with sorafenib as a second-line treatment may benefit patients with metastatic RCC, especially in subjects >?65?years old.

SUBMITTER: Martin-Aguilar AE

PROVIDER: S-EPMC7786959 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Sorafenib as a second-line treatment in metastatic renal cell carcinoma in Mexico: a prospective cohort study.

Martín-Aguilar Ana Elena AE Núñez-López Haidé H Ramirez-Sandoval Juan C JC

BMC cancer 20210105 1

<h4>Background</h4>Sequential inhibition of the vascular endothelial growth factor (VEGF) pathway with sorafenib could be useful for patients with metastatic renal cell carcinoma (RCC). Our aim was to determine the activity and tolerability of sorafenib as a second-line therapy in advanced RCC initially treated with a different VEGF-tyrosine kinase inhibitor (TKI).<h4>Methods</h4>A prospective observational cohort in Mexico (2012-2019). We included 132 subjects with metastatic RCC and who had pr ...[more]

PMID: 33402115

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Project description:Currently, conventional treatments for metastatic RCC (mRCC) include immune-based combination regimens and/or targeted therapies, the latter mainly acting on angiogenesis, a key element of the process of tumor growth and spread. Although these agents proved able to improve patients' outcomes, drug resistance and disease progression are still experienced by a substantial number of VEGFR-TKIs-treated mRCC patients. Following the inhibition of the VEGF/VEGFRs axis, two strategies have emerged: either specifically targeting resistance pathways, at the same time continuing to inhibit angiogenesis, or using a completely different approach aimed at re-activating the immune system through the use of inhibitors of specific negative immune checkpoints. These two approaches, practically represented by the use of either cabozantinib or nivolumab, seem to remain a rational therapeutic approach also when first-line immune-based combinations are used. The objective of this study is to design a preferential therapeutic pathway for the second-line treatment of mRCC. The procedure applied in this project was a group discussion, based on the Nominal Group Technique (NGT) method in a meeting session, aimed at defining the therapeutic choice for the second-line treatment of mRCC. The NGT process defined the most relevant parameters that, according to the interviewed panelists, clinicians should consider for the selection of the second-line therapy in the context of advanced renal cell carcinoma of mRCC. The algorithm developed for the treatment selection as a result of this process should thus be considered by clinicians as reference for therapy selection.Plain language summaryThe result of this paper was the definition of an algorithm intended to suggest a preferential therapeutic pathway considering both the outputs of the Nominal Group Technique (NGT) process and the actual clinical practice and the experience of selected panelists. During the NGT process and the discussion phase, panelists defined the most important parameters to be included in the algorithm that are important for the treatment definition. Cabozantinib and nivolumab are identified as the most reasonable therapeutic options for patients progressing after first-line treatment and are the medication options included in the algorithm for therapy selection.

Project description:An unmet medical need exists for patients with metastatic renal cell carcinoma who have progressed on VEGF-targeted and mTOR-inhibitor therapies. Fibroblast growth factor (FGF) pathway activation has been proposed as a mechanism of escape from VEGF-targeted therapies. Dovitinib is an oral tyrosine-kinase inhibitor that inhibits VEGF and FGF receptors. We therefore compared dovitinib with sorafenib as third-line targeted therapies in patients with metastatic renal cell carcinoma.In this multicentre phase 3 study, patients with clear cell metastatic renal cell carcinoma who received one previous VEGF-targeted therapy and one previous mTOR inhibitor were randomly assigned through an interactive voice and web response system to receive open-label dovitinib (500 mg orally according to a 5-days-on and 2-days-off schedule) or sorafenib (400 mg orally twice daily) in a 1:1 ratio. Randomisation was stratified by risk group and region. The primary endpoint was progression-free survival (PFS) assessed by masked central review. Efficacy was assessed in all patients who were randomly assigned and safety was assessed in patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT01223027.284 patients were randomly assigned to the dovitinib group and 286 to the sorafenib group. Median follow-up was 11·3 months (IQR 7·9-14·6). Median PFS was 3·7 months (95% CI 3·5-3·9) in the dovitinib group and 3·6 months (3·5-3·7) in the sorafenib group (hazard ratio 0·86, 95% CI 0·72-1·04; one-sided p=0·063). 280 patients in the dovitinib group and 284 in the sorafenib group received at least one dose of study drug. Common grade 3 or 4 adverse events included hypertriglyceridaemia (38 [14%]), fatigue (28 [10%]), hypertension (22 [8%]), and diarrhoea (20 [7%]) in the dovitinib group, and hypertension (47 [17%]), fatigue (24 [8%]), dyspnoea (21 [7%]), and palmar-plantar erythrodysaesthesia (18 [6%]) in the sorafenib group. The most common serious adverse event was dyspnoea (16 [6%] and 15 [5%] in the dovitinib and sorafenib groups, respectively).Dovitinib showed activity, but this was no better than that of sorafenib in patients with renal cell carcinoma who had progressed on previous VEGF-targeted therapies and mTOR inhibitors. This trial provides reference outcome data for future studies of targeted inhibitors in the third-line setting.Novartis Pharmaceuticals Corporation.

Dataset Information

Sorafenib as a second-line treatment in metastatic renal cell carcinoma in Mexico: a prospective cohort study.

Background

Methods

Results

Conclusion

Publications

Sorafenib as a second-line treatment in metastatic renal cell carcinoma in Mexico: a prospective cohort study.

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