Emerging growth factor receptor antagonists for the treatment of renal cell carcinoma.
The landscape of systemic treatment for metastatic renal cell carcinoma (RCC) has dramatically changed with the introduction of targeted agents including vascular endothelial growth factor (VEGF) inhibitors. Recently, multiple new agents including growth factor receptor antagonists and a checkpoint inhibitor were approved for the treatment of refractory metastatic RCC based on encouraging benefit shown in clinical trials. Areas covered: The background and biological rationale of existing treatment options including a brief discussion of clinical trials which led to their approval, is presented. This is followed by reviewing the limitations of these therapeutic options, medical need to develop new treatments and major goals of ongoing research. We then discuss two recently approved growth factor receptor antagonists i.e. cabozantinib and lenvatinib, and a recently approved checkpoint inhibitor, nivolumab, and issues pertaining to drug development, and future directions in treatment of metastatic RCC. Expert opinion: Recently approved growth factor receptor antagonists have shown encouraging survival benefit but associated drug toxicity is a major issue. Nivolumab, a programmed death 1 (PD-1) checkpoint inhibitor, has similarly shown survival benefit and is well tolerated. With multiple options now available in this patient population, the right sequence of these agents remains to be determined.
a Taussig Cancer Institute , Cleveland Clinic , Cleveland , OH , USA.
Haris
H
Zahoor
a Taussig Cancer Institute , Cleveland Clinic , Cleveland , OH , USA.
Brian I
BI
Rini
D000813:Anilides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D017277:Drug Approval; D015195:Drug Design; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009362:Neoplasm Metastasis; D000077594:Nivolumab; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D011725:Pyridines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D011804:Quinolines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D017978:Receptors, Growth Factor / Q000037:antagonists & inhibitors
D000813:Anilides; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D011725:Pyridines; D011804:Quinolines; D017978:Receptors, Growth Factor; C558660:cabozantinib; D000077594:Nivolumab; C531958:lenvatinib
Metastatic renal cell carcinoma; PD-1; TKI; VEGF; cabozantinib; growth factor receptor antagonists; immunotherapy; lenvatinib; nivolumab; targeted agents