Response-adaptive immunotherapy approach falls short in metastatic kidney cancer

October 30, 2020
Jason M. Broderick

Upfront nivolumab followed by response-dependent sequential use of ipilimumab did not optimize treatment outcomes in patients with advanced renal cell carcinoma.

A strategy of upfront nivolumab (Opdivo) followed by response-dependent sequential use of ipilimumab (Yervoy) did not provide a benefit in patients with advanced renal cell carcinoma (RCC), according to findings from the phase 2 OMNIVORE trial published in the Journal of Clinical Oncology.1

In the study, 57 patients who had stable disease (SD) or progressive disease (PD) after ≤6 months of upfront nivolumab were treated with 2 doses of ipilimumab. Among these patients, there were no complete responses (CRs) and only 2 (4%) patients converted from SD or PD to a partial response (PR).

“Currently, our data do not support a response-adaptive strategy for checkpoint blockade in advanced RCC,” first study author Rana R. McKay, MD, assistant professor of medicine and medical oncologist at the University of California, San Diego, and coauthors wrote. “Upfront dual checkpoint blockade is suggested in patients eligible to receive this treatment.”

Overall, the study included 83 patients with advanced RCC, of whom 51% were treatment-naïve, 67% had intermediate/poor-risk disease, and 96% had clear-cell histology. Prior treatment with an immune checkpoint inhibitor was not allowed.

All 83 patients were initially treated with nivolumab monotherapy, with subsequent treatment based on a patient’s response to the PD-1 inhibitor. Patients achieving a confirmed CR or PR within 6 months stopped receiving nivolumab and were assigned to observation. Patients with SD or PD at 6 months were administered ipilimumab.

The median follow-up time was 19.5 months. Induction nivolumab resulted in an objective response rate of 14% (12 of 83), including a confirmed PR in 10 patients and an unconfirmed PR in 2 patients. These 12 patients discontinued nivolumab and were assigned to observation.

There were 14 patients who were not allocated to either study arm after nivolumab induction. Seven of these patients had PD and 7 had toxicity that was too severe.

The remaining 69% (57 patients) of the study population was assigned to ipilimumab after best response of SD or PD on induction nivolumab. The 2 patients in this group who converted to a confirmed PR had PD after nivolumab induction, and both had prior therapy before study enrollment. The duration of response for the 2 patients was 9.2 and 10.9 months, respectively, and both patients eventually had to discontinue ipilimumab due to PD.

Despite their lack of success with this response-adaptive strategy, the investigators are continuing to explore new approaches—such as using novel biomarkers of response and resistance—to improve upon treatment standards in advanced RCC.

Nivolumab and ipilimumab are currently approved by the FDA for combination use as a dual checkpoint blockade in the first-line setting for the treatment of patients with intermediate- or poor-risk, advanced RCC. Nivolumab is also approved by the FDA for single-agent use in patients with advanced RCC who have previously received antiangiogenic therapy.

Reference

1. McKay RR, McGregor BA, Xie W, et al. Optimized management of nivolumab and ipilimumab in advanced renal cell carcinoma: a response-based phase II study (OMNIVORE) [published online ahead of print October 27, 2020]. J Clin Oncol doi: 10.1200/JCO.20.02295



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