Emerging therapeutics in refractory renal cell carcinoma.
BACKGROUND
Metastatic renal cell carcinoma (mRCC) has seen the introduction of numerous new treatments over the past decade. However, the efficacy of these therapies has plateaued, and new treatment options are needed for the majority of patients with mRCC whose disease inevitably progresses through one or more standard therapies ('refractory' mRCC). Recently approved agents in this space have shown great promise.


METHODS
This article reviews the evidence behind current management strategies for mRCC. After reviewing clinical trials that established current first-line therapies and agents used in the refractory setting, we address new ideas for the treatment of refractory disease including combination therapies and novel targeted agents. In particular, we focus on targeted immunotherapy in refractory mRCC. We conclude by considering future directions in combination treatments utilizing these novel agents.


CONCLUSIONS
Numerous approaches have produced tangible benefits for the treatment of patients with mRCC. These include development of next generation VEGFR/TKIs, targeted immunotherapy agents, and the development of combined regimens. In particular, immunotherapy agents targeting the PD1/PD-L1 pathway have shown great promise with a robust survival advantage seen in patients treated with nivolumab. A tolerable side effect profile of immunotherapy agents makes them amenable for use in combination therapies and ongoing trials are addressing this question.
a Department of Hematology and Oncology , Cleveland Clinic, Taussig Cancer Institute , Cleveland , OH , USA.
Vadim S
VS
Koshkin
a Department of Hematology and Oncology , Cleveland Clinic, Taussig Cancer Institute , Cleveland , OH , USA.
Brian I
BI
Rini
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000628:therapy*; D003131:Combined Modality Therapy; D006801:Humans; D007167:Immunotherapy / Q000379:methods / Q000639:trends; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000628:therapy*; D058990:Molecular Targeted Therapy / Q000379:methods / Q000639:trends; D000077594:Nivolumab; D035703:Therapies, Investigational / Q000379:methods / Q000639:trends*
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000077594:Nivolumab
Immunotherapy; PD-1/PD-L1 pathway; VEGFR/TKI; cabozantinib; checkpoint inhibitor; metastatic renal cell carcinoma; nivolumab; targeted therapy