Nivolumab Looks Promising for Metastatic Renal Cell Carcinoma

April 2, 2015
Lauren Evoy Davis
Lauren Evoy Davis

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.

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.

 

 

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