First-Line Treatment of Metastatic Clear Cell Renal Cell Carcinoma: What Are the Most Appropriate Combination Therapies?

Vano, Yann; Ladoire, Sylvain; Elaidi, Réza; Dermeche, Slimane; Eymard, Jean‐Christophe; Falkowski, Sabrina; Gross‐Goupil, Marine; Malouf, Gabriel G.; Narciso, Bérengère; Sajous, Christophe; Tartas, Sophie; Voog, Éric; Ravaud, Alain

doi:10.3390/cancers13215548

Cited by 13 publications

(11 citation statements)

References 48 publications

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“…At transcriptomic level, assigning ccRCC biopsies into either immunogenic or angiogenic signatures may indicate which treatment could be most beneficial for individual patients. The introduction of ICIs has significantly changed the therapeutic landscape for patients with advanced ccRCC 56,57 , resulting in a clinical need to select patients who will benefit either from angiogenic or immunogenic treatment 17 . These data could assist clinical decision making when choosing the optimal treatment strategy for the individual patient with advanced ccRCC.…”

Section: Discussionmentioning

confidence: 99%

“…However, there are considerable interindividual differences in outcome, and only a minority of patients experience durable responses 14 . For patients with advanced ccRCC, treatment decision making is nowadays guided by the International Metastatic RCC Database Consortium (IMDC) criteria [15][16][17] . These criteria include only clinical patient characteristics (i.e.…”

Section: Introductionmentioning

confidence: 99%

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The genomic and transcriptomic landscape of advanced renal cell cancer for individualized treatment strategies

Joode

Geer

Leenders

et al. 2022

Preprint

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The genomic landscape of advanced renal cell cancer (RCC) was characterized for 91 patients to identify actionable targets and signatures by combining whole-genome sequencing (WGS) with matched RNA sequencing (RNA-Seq). WGS data were analyzed for somatic small variants, copy-number alterations (CNAs) and structural variants. Somatic aberrations were analyzed for driver genes, CNA drivers, mutational signatures, catastrophic events and fusion genes. For papillary and clear cell RCC, potential actionable drug targets were detected by WGS in 89% and 100% of the patients, respectively. RNA-Seq data of clear cell and papillary RCC were clustered according to a previously developed angio-immunogenic gene signature. WGS and RNA-Seq may improve therapeutic decision making for most patients with advanced RCC, including patients with non-clear cell RCC for whom no standard treatment is available to date. Prospective clinical trials are needed to evaluate the impact of genomic and transcriptomic diagnostics on survival outcome for advanced RCC patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The genomic and transcriptomic landscape of advanced renal cell cancer for individualized treatment strategies

Joode

Geer

Leenders

et al. 2022

Preprint

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“…So far, the only additional information available on the most appropriate combination of therapies – mostly based on complete response rates, early progression, rapid control of symptoms and the initial evolution of the PFS curve over the first 3 months of treatment – comes from position papers from experts in the field. 44 …”

Section: Clinical Efficacymentioning

confidence: 99%

An Evaluation of Cabozantinib for the Treatment of Renal Cell Carcinoma: Focus on Patient Selection and Perspectives

Iaxx¹,

Lefort²,

Domblides³

et al. 2022

TCRM

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Cabozantinib is an oral tyrosine kinase inhibitor (TKI) with activity against several receptors involved in the angiogenesis pathway, including vascular endothelial growth factor receptor (VEGFR), c-MET and AXL. The antiangiogenic properties of cabozantinib led to its use as a monotherapy for the treatment of metastatic renal cell cancer (RCC), and quickly resulted in this treatment becoming part of the standard of care for these tumors. Since the advent of immune checkpoint inhibitors (ICIs), new standards of care have emerged in first-line settings, involving dual ICI or ICI–VEGF-TKI (including ICI–cabozantinib) combination treatments, and leading to a more complex algorithm of care. Cabozantinib remains an option in second-line settings and is still a first-line standard of care treatment in cases where the use of ICIs is contraindicated. This review focuses on the selection of patients who may benefit most from cabozantinib therapy, including those with bone and brain metastases and those with a non-clear cell RCC histology. The need to consider disease-related symptoms, comorbidities, age, drug interactions and biomarker analyses in the choice of therapeutic strategy is also highlighted. Finally, the perspectives for the use of cabozantinib in RCC treatment are discussed.

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“…ICI-based combination therapy, consisting of either dual ICIs or ICI plus tyrosine kinase inhibitor (TKI), has been demonstrated to markedly improve prognostic outcomes of treatment-naïve aRCC patients. ICI was also shown to be effective in aRCC patients previously treated with TKIs [4,5]. In major clinical guidelines, ICI or ICI-based combination regimens are widely recommended as standard systemic therapies against aRCC [6,7].…”

Section: Introductionmentioning

confidence: 99%

Assessments of optimal timing for combined therapy with axitinib and immune check point inhibitor in a mouse renal cell carcinoma model

Watanabe

Matsushita

Tamura

et al. 2022

Preprint

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Background Recently, several types of systemic therapy using tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor (ICI) have been performed for advanced renal cell carcinoma (aRCC) patients; however, the optimal strategy of sequential treatment with these agents has not been well established. The objective of this study was to determine the optimal timing for the introduction of TKI and ICI using a mouse RCC, RenCa model. Materials and Methods The effects of combined treatment of TKI and/or ICI with axitinib, anti-mouse programmed death (PD)-1, or PD-ligand 1 (PD-L1) antibody on tumor growth and survival after subcutaneous and intravenous injection of RenCa cells, respectively, were compared according to three different treatment schedules: simultaneous administration, initial axitinib administration, and initial ICI administration. Infiltrating patterns of lymphocytes into tumors after combined treatments were evaluated by immunohistochemical staining. Results In both the patients with anti-PD-1 and anti-PD-L1 antibodies, significantly marked inhibitory effects on subcutaneous growth of tumors were observed in the simultaneous and initial ICI administration, but not the initial axitinib administration, compared to those in the control without treatment. Survival intervals of mice after intravenous injection of RenCa cells were significantly longer in the simultaneous and initial ICI administration, but not the initial axitinib administration, compared to the control. Furthermore, both CD8 + to CD3 + and CD8 + to CD11b + T-lymphocyte ratios in subcutaneous RenCa tumors were significantly higher in the simultaneous and initial ICI administration, but not the initial axitinib administration, compared to the control. Conclusions Favorable control against aRCC progression may be achieved by administering TKI and ICI simultaneously or ICI followed by TKI.

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First-Line Treatment of Metastatic Clear Cell Renal Cell Carcinoma: What Are the Most Appropriate Combination Therapies?

Cited by 13 publications

References 48 publications

The genomic and transcriptomic landscape of advanced renal cell cancer for individualized treatment strategies

The genomic and transcriptomic landscape of advanced renal cell cancer for individualized treatment strategies

An Evaluation of Cabozantinib for the Treatment of Renal Cell Carcinoma: Focus on Patient Selection and Perspectives

Assessments of optimal timing for combined therapy with axitinib and immune check point inhibitor in a mouse renal cell carcinoma model

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