Opdivo-Yervoy Combination Shows Promise in Certain Patients with Previously Treated RCC

The combination therapy of Opdivo (nivolumab) and Yervoy (Ipilimumab) demonstrated overall antitumor activity in two key areas and had favorable toxicity in patients with metastatic renal cell carcinoma (RCC) who had previously received treatment with immune checkpoint inhibitors (ICI), according to data published in the Journal of Clinical Oncology.

Immune checkpoint inhibitors are a standard therapy for patients with metastatic RCC, however, the safety and overall activity in the popular combination of Opdivo and Yervoy had not been measured for patients with metastatic RCC who previously received ICI treatment targeting their PD-1 pathway.

This study analyzed 45 patients with metastatic RCC to see how the combination impacted them. After a 12-month follow up, the researchers identified an objective response rate of 20% and noted that median progression free survival (PFS) was 4 months. Moreover, the median duration of response was 7 months.

While the combination, and other ICI treatments, is a standard therapy for this patient population, many patients who have received prior anti-PD-1 targeted therapies will eventually progress and require more treatment, according to the study authors. As a result, researchers aimed to see how the combination would react in patients that needed further treatment by using a treatment already approved for many in this population.

“This series demonstrates that patients with metastatic RCC can achieve objective responses to salvage ipilimumab and nivolumab after prior anti—PD-1 pathway–targeted therapy,” the authors explained. “It is important to note that although a small proportion of patients had an objective response to salvage ipilimumab and nivolumab, the responses to salvage ipilimumab and nivolumab were durable in the majority of responders, and several patients derived clinical benefit even without achieving RECIST-defined (partial response).”

The safety profile of this therapy was considered tolerable by the researchers, but also warranted caution for further use. Patients received the combination for a median of four months. Sixty-nine percent of the patients received all four doses of the combintion. Treatment was delayed in four patients and discontinued in six due to immune-related side effects. The most common of these side effects included diarrhea (16%), rash (13%), hepatotoxicity (liver damage) (9%) and pneumonitis (7%). Serious or severe side effects included hepatotoxicity (7%) and pneumonitis, rash, diarrhea, thrombocytopenia and colitis (2% each).

“The lack of complete responses, high rate of (progressive disease), and the potential for toxicity provide caution to the application of these data to select patients,” researchers concluded. “Prospective clinical trials are needed to further define the clinical activity of checkpoint inhibition after previous ICI exposure in metastatic RCC.”