Safety of Immune Checkpoint Inhibitors With Nephrectomy in mRCC

June 4, 2019

A pilot study evaluated cytoreductive surgery combined with immune checkpoint therapy in patients with metastatic renal cell carcinoma.

In a pilot study, cytoreductive surgery combined with immune checkpoint therapy led to improved outcomes and appeared to be safe compared with immune checkpoint therapy alone in patients with metastatic renal cell carcinoma (mRCC). Cytoreductive surgery has been shown to benefit mRCC patients, but it has not been studied in combination with immune checkpoint therapy. The results suggest that the strategy should be tested in a phase III trial.

The results of the open-label trial (abstract 4501) were presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 31–June 4 in Chicago. It included 104 patients, nearly all treatment naïve, who were eligible for cytoreductive nephrectomy, metastasectomy, or post-treatment biopsy. They were randomized 2:3:2 to nivolumab, nivolumab plus bevacizumab, or nivolumab plus ipilimumab for 4 to 6 weeks. Patients then underwent cytoreductive surgery or post-treatment biopsy, followed by nivolumab maintenance therapy that lasted up to 2 years.

Of 43 patients who underwent surgery during the trial, 91% had a nephrectomy. In addition, 12% had undergone a previous cytoreductive nephrectomy, compared with 49% of the 61 patients who did not undergo surgery.

A combination endpoint called best overall response (BOR), which included complete response and partial response, was 59% for nivolumab, 44% for nivolumab + bevacizumab, and 43% for nivolumab + ipilimumab. BOR calculated to include the effect of surgery was 86% in nivolumab, 88% in nivolumab + bevacizumab, and 69% in nivolumab + ipilimumab.

The 2-year overall survival rate was 72% in the nivolumab arm (standard error, 8%), 60% in the nivolumab + bevacizumab arm (SE, 8%), and 56% in the nivolumab + ipilimumab arm (SE, 10%). Surgical patients fared better overall compared with non-surgical patients, with 2-year OS rates of 84% (SE, 6%) vs 46% (SE, 7%), respectively.  

In total, 28% of the nivolumab group had grade 3 or higher treatment-related toxicity, compared with 38% in the nivolumab + bevacizumab group, and 43% in nivolumab + ipilimumab group. A lipase increase occurred in 17% of the bevacizumab group, 11% of the nivolumab + bevacizumab group, and 17% of the nivolumab + ipilimumab group. The frequency of hypertension was 0%, 18%, and 3%, respectively.

Asked for comment on the study, Robert Dreicer, MD, deputy director of the University of Virginia Cancer Center, was lukewarm about the results. “They were able to say we can deliver these more modern systemic therapies in the context of removing the kidney, and do it safely. There was activity, which is not surprising – all of the drugs have activity in advanced disease,” Dreicer told Cancer Network.

He cited a similar study presented at ASCO last year, which tested the use of sunitinib in the context of nephrectomy, and found that patients with advanced kidney cancer had a longer median overall survival when treated with sunitinib without surgery (18.4 months) than when sunitinib was combined with surgery (13.9 months). “The next step is to take one of the modern therapies, (ipilimumab + nivolumab), bevacizumab, or a (newer) checkpoint inhibitor, and do the same study. Will that get done? It’s unclear. But this set the stage to do that study,” said Dreicer.