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Second-Line Treatment Landscape for Renal Cell Carcinoma: A Comprehensive Review.

ABSTRACT: The management of advanced clear-cell renal cell carcinoma has steadily improved over the past decade with the introduction of antiangiogenic and targeted therapies. Recently, three new therapies have been approved for use as second-line options that further advance the treatment armamentarium: nivolumab, a monoclonal antibody targeting the programmed cell death receptor; cabozantinib, a small-molecule tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptor (VEGFR), MET, and AXL; and lenvatinib, a small-molecule TKI of VEGF and fibroblast growth factor receptors that is used in combination with everolimus, an inhibitor of the mechanistic target of rapamycin. Together, these and previously approved second-line treatments offer clinicians the ability to better individualize treatment for patients after progression on first-line VEGFR-targeted therapies. In this comprehensive review, we discuss the efficacy and safety results from the pivotal trials of these newly approved therapies, including the quality of study design, the level of evidence, subgroup analyses, and how these data can help to guide clinicians to select the most appropriate second-line therapy for their patients.

Implications for practice

This review article provides the reader with a comprehensive overview of current treatment options for patients with advanced clear-cell renal cell carcinoma (RCC) whose disease has progressed after their first therapy. As many patients with RCC experience disease progression with initial treatments, effective second-line therapies are critical. Nivolumab, cabozantinib, and lenvatinib plus everolimus have recently been approved as second-line treatments. The new agents discussed in this review increase the therapeutic options available and provide physicians with opportunities to individualize treatments for their patients, with a view to improving disease control and survival outcomes.

SUBMITTER: Tannir NM

PROVIDER: S-EPMC5947457 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Second-Line Treatment Landscape for Renal Cell Carcinoma: A Comprehensive Review.

Tannir Nizar M NM Pal Sumanta K SK Atkins Michael B MB

The oncologist 20180227 5

The management of advanced clear-cell renal cell carcinoma has steadily improved over the past decade with the introduction of antiangiogenic and targeted therapies. Recently, three new therapies have been approved for use as second-line options that further advance the treatment armamentarium: nivolumab, a monoclonal antibody targeting the programmed cell death receptor; cabozantinib, a small-molecule tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptor (VEGFR), MET, a ...[more]

PMID: 29487224

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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.

Dataset Information

Second-Line Treatment Landscape for Renal Cell Carcinoma: A Comprehensive Review.

Implications for practice

Publications

Second-Line Treatment Landscape for Renal Cell Carcinoma: A Comprehensive Review.

Similar Datasets

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