Nivolumab Looks Promising for Metastatic Renal Cell Carcinoma

Metastatic renal cell carcinoma (mRCC) can have a grim outcome, but the good news is that nivolumab (Opdivo) has demonstrated antitumor activity in patients with this disease.

A phase II clinical trial of nivolumab, a programmed cell death protein-1 (PD-1) immune checkpoint inhibitor antibody, showed positive results when given to patients who had previously received vascular endothelial growth factor (VEGF) inhibitor therapy.¹ Patients who have undergone treatments such as VEGF, have experienced progression-free survival (PFS), but only for a short amount of time--which highlights the need for new treatment options. Nivolumab restores T-cell function which contributes to immune defenses in two major ways: direct and regulate immune responses, and directly attacks infected cells and cancer cells.²

The results were first presented at the 2014 Annual Meeting of the American Society of Clinical Oncology (ASCO), and published in the Journal of Clinical Oncology ¹ and The ASCO Post.³

A total of 168 patients with clear cell renal cell carcinoma were randomly assigned to receive various doses of nivolumab in this three-arm study:  0.3- (n = 60), 2- (n = 54), and 10-mg/kg (n = 54). Of those patients, 118 (70%) had received more than one prior systemic regimen, such as VEFG. One key inclusion criteria included disease progression during or after last therapy received, and within 6 months of enrollment, but no more than three prior treatment regimens in the metastatic setting. Median PFS was 2.7, 4.0, and 4.2 months, respectively (P = .9). Objective response rates (ORRs) were 20%, 22%, and 20%. Median overall survival (OS) was 18.2 months (80% CI, 16.2 to 24.0 months), 25.5 months (80% CI, 19.8 to 28.8 months), and 24.7 months (80% CI, 15.3 to 26.0 months), respectively.

Toxicity levels, which are a concern for all patients, but especially those experiencing metastatic disease, were tolerable. These favorable outcomes opened the door for a phase III trial which will continue to study safety and efficacy for this high-risk patient population.

Currently, a phase III trial comparing Nivolumab vs Everolimus using an OS primary end point in patients with mRCC pretreated with antiangiogenic therapy is ongoing. Encouraging antitumor activity was observed in a phase IB trial evaluating the combination of nivolumab and ipilimumab in patients with mRCC. A phase III trial using OS as a primary end point is under way to evaluate nivolumab combined with ipilimumab vs sunitinib in the first-line setting.

References:

• Motzer RJ, Rini BI, McDermott DF, et al. (2014). Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial. Journal of Clinical Oncology.
• National Institute of Allergy and Infectious Disease. (2008). Immune System: T-Cells.
• Stenger M. (2015). Nivolumab Shows Activity in Previously Treated Metastatic Renal Cell Carcinoma. The ASCO Post, 6(4).