Evaluating Front-line Ipilimumab, Nivolumab for Patients With Metastatic RCC

For patients with treatment-naïve, intermediate- and poor-risk metastatic renal cell carcinoma (RCC), ipilimumab plus nivolumab is an approved treatment option. However, a lack of research persists on the duration of therapy as well as the safety and efficacy of reinduction at progression.

A phase 2 study from Moshe C. Ornstein, MD, and colleagues published in Clinical Genitourinary Cancer investigated the effects of intermittent ipilimumab plus nivolumab with reinduction at progression in patients with metastatic RCC.

Patients with treatment-naïve mRCC received induction ipilimumab plus nivolumab followed with up to 24 weeks of maintenance nivolumab. Those who demonstrated either a partial response (PR) or complete response (CR) were deemed eligible for inclusion and underwent a treatment-free observation period. Those without disease progression remained off therapy. Upon disease progression, patients were re-challenged with 2 doses of ipilimumab/nivolumab every 3 weeks.

Of the 9 participants, 89% were male, 67% presented with a clear-cell histology, and 78% were intermediate-risk according to International Metastatic RCC Database Consortium criteria. Prior to enrollment, the response to ipilimumab plus nivolumab followed by nivolumab maintenance was 33% CR and 67% PR.

Across the participants, 78% remained off therapy, with Dr. Ornstein and colleagues reporting a median treatment-free interval of 34.3 months.

Investigators also noted that 2 patients demonstrated disease progression while off therapy and underwent treatment with 2 cycles of reinduction ipilimumab and nivolumab. Following reintroduction, no grade 3 or higher toxicities were reported. For both patients, disease progression was reported upon their first scans following reintroduction.

“This prospective study demonstrates that patients with a radiographic response to ipilimumab/nivolumab can have prolonged treatment-free intervals,” the researchers wrote. “Further studies of de-escalation strategies are warranted.”