Sarcomatoid Renal Cell Carcinoma: The Present and Future of Treatment Paradigms

Sarcomatoid renal cell carcinoma (sRCC) is an aggressive form of kidney cancer that is associated with poor prognosis. It can arise from any histologic type of renal cell carcinoma. The majority of cases will present with advanced or metastatic disease requiring systemic therapy. Nephrectomy is the treatment of choice in locally resectable disease. The therapeutic options for sRCC have evolved in the past decade. Cytotoxic chemotherapy and monotherapy with targeted therapy (VEGF and mTOR) have historically shown poor response rates and survival in the treatment of metastatic sRCC. The use of checkpoint inhibitors and their combination with targeted therapy against VEGF has changed the landscape and outcomes for renal cell carcinoma. Given the rarity of sRCC most of the data on treatment is from small cohorts or extrapolation from larger clinical trials. The benefit from the combination of checkpoint inhibitors and targeted therapy to VEGF has shown promise in the sRCC population in post hoc analysis of large clinical trials. Future research focusing on further characterizing the unique biologic and clinical features of sRCC is critical in advancing the knowledge and developing effective therapy to improve clinical outcomes and survival.

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Patients with sarcomatoid renal cell carcinoma – re-defining the first-line of treatment: A meta-analysis of randomised clinical trials with immune checkpoint inhibitors

European Journal of Cancer ◽

10.1016/j.ejca.2020.06.008 ◽

2020 ◽

Vol 136 ◽

pp. 195-203 ◽

Cited By ~ 5

Author(s):

Roberto Iacovelli ◽

Chiara Ciccarese ◽

Emilio Bria ◽

Sergio Bracarda ◽

Camillo Porta ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Clinical Trials ◽

Cell Carcinoma ◽

Immune Checkpoint ◽

Renal Cell ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Meta Analysis ◽

First Line ◽

Sarcomatoid Renal Cell Carcinoma

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The Future of Immunotherapy-Based Combination Therapy in Metastatic Renal Cell Carcinoma

Cancers ◽

10.3390/cancers12010143 ◽

2020 ◽

Vol 12 (1) ◽

pp. 143 ◽

Cited By ~ 7

Author(s):

Rohan Garje ◽

Josiah An ◽

Austin Greco ◽

Raju Kumar Vaddepally ◽

Yousef Zakharia

Keyword(s):

Renal Cell Carcinoma ◽

Clinical Trials ◽

Targeted Therapy ◽

Cell Carcinoma ◽

Renal Cell ◽

Cytotoxic T Lymphocyte ◽

Checkpoint Inhibitors ◽

Interleukin 2 ◽

Complete Response ◽

High Dose

In the past two decades, there has been a significant improvement in the understanding of the molecular pathogenesis of Renal Cell Carcinoma (RCC). These insights in the biological pathways have resulted in the development of multiple agents targeting vascular endothelial growth factor (VEGF), as well as inhibitors of the mammalian target of the rapamycin (mTOR) pathway. Most recently, checkpoint inhibitors were shown to have excellent clinical efficacy. Although the patients are living longer, durable complete responses are rarely seen. Historically, high dose interleukin 2 (IL2) therapy has produced durable complete responses in 5% to 8% highly selected patients—albeit with significant toxicity. A durable complete response is a surrogate for a long-term response in the modern era of targeted therapy and checkpoint immunotherapy. Numerous clinical trials are currently exploring the combination of immunotherapy with various targeted therapeutic agents to develop therapies with a higher complete response rate with acceptable toxicity. in this study, we provide a comprehensive review of multiple reported and ongoing clinical trials evaluating the combination of PD-1/PD-L1 inhibitors with either ipilimumab (a cytotoxic T-lymphocyte-associated protein 4, CTLA-4 inhibitor) or with anti-VEGF targeted therapy.

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