New treatment options for metastatic renal cell carcinoma with prior anti-angiogenesis therapy

Abstract

Angiogenesis is a critical process in the progression of advanced renal cell carcinoma. Agents targeting angiogenesis have played a primary role in the treatment of metastatic renal cell carcinoma. However, resistance to anti-angiogenesis therapy almost always occurs, and major progress has been made in understanding its underlying molecular mechanism. Axitinib and everolimus have been used extensively in patients whom have had disease progression after prior anti-angiogenesis therapy. Recently, several new agents have been shown to improve overall survival in comparison with everolimus. This review provides an in-depth summary of drugs employable in the clinical setting, the rationale to their use, and the studies conducted leading to their approval for use and provides perspective on the paradigm shift in the treatment of renal cell carcinoma. Highlighted are the newly approved agents cabozantinib, nivolumab, and lenvatinib for advanced renal cell carcinoma patients treated with prior anti-angiogenesis therapy.

Outcomes of Patients with Metastatic Renal Cell Carcinoma Treated with Targeted Therapy After Immuno-oncology Checkpoint Inhibitors

“…This is reflective of the current treatment landscape, where nivolumab was approved in mRCC patients who received prior antiangiogenic therapy and nivolumab plus ipilimumab was approved as frontline treatment for advanced RCC patients with IMDC intermediate or poor risk. IO therapy including nivolumab plus ipilimumab has an antitumor effect through activation of the endogenous immune system to target cancer at the cellular level by enabling checkpoint inhibition [26]. A hypothesis-generating prospective trial of IO therapy via PD-1/PD-L1 blockade demonstrated an increase in lymphocytic presence and reversal of T-cell exhaustion [27].…”

Sunitinib for Metastatic Renal Cell Carcinoma: A Systematic Review and Meta-Analysis of Real-World and Clinical Trials Data

“…However, sunitinib remains one of several recommended first-line treatments for patients with favorable risk mRCC [16][17][18]. Choosing the optimal sequence of treatment has subsequently become increasingly complex for the clinician and the patient [19,20].…”

Risk of Liver Toxicity with Nivolumab Immunotherapy in Cancer Patients

“…Neoplasms are highly immunogenic, and immunotherapy plays a role in the immune signaling interface of the tumor microenvironment. Neoplastic cells have the unique ability to evade immune cell surveillance and undergo uninhibited and unregulated cell growth [4]. The principle underlying PD-1 inhibitors entails immune checkpoint blockade, which reduces inhibitory signaling DOI: 10.1159/000486679 and in turn, restores the patient's endogenous tumor-specific T-cell-mediated immune responses [5].…”

“…Nivolumab, a humanized immunoglobulin G4 PD-1 immune checkpoint inhibitor, enhances T-cell function, and results in antitumor activity with durable responses seen in several trials through its clinical development [6]. The success of nivolumab and its class-equivalent PD-1 inhibitors has changed the therapeutic landscape for multiple cancers and currently holds the United States Food and Drug Administration approval for the treatment of melanoma, squamous non-small cell lung cancer, Hodgkin's lymphoma, and metastatic renal cell carcinoma (RCC) [4].…”