Response patterns with immunotherapy may differ from those of other treatments in patients with metastatic renal cell carcinoma (RCC), according to a study published in the Journal of the American Medical Association.1 Investigators found that sustained reductions in tumor burden or stabilization in the sizes of target lesions may be possible with continued nivolumab (Opdivo) treatment, following initial disease progression in patients with metastatic RCC. The study suggests that a significant number of patients may benefit from continued immunotherapy beyond Response Evaluation Criteria in Solid Tumors (RECIST)-defined first progression.

“I was not surprised since the results are consistent with our experience from the clinical trials with nivolumab, demonstrating benefits for patients who continue therapy beyond first progression,” said study investigator Saby George, MD, associate professor of oncology in the Department of Medicine at Roswell Park Cancer Institute in Buffalo, New York.

The researchers investigated the checkpoint inhibitor, nivolumab, in the treatment of 168 patients in a blinded, randomized, multicenter phase 2 dose-ranging clinical trial. The median age of the patients was 61 and 72% were male. The trial was conducted at academic centers in the United States, Canada, Finland, and Italy.

Continue Reading

It was found that 154 patients experienced progression and 36 were treated beyond first progression. Twenty-six patients were treated beyond first progression for 6 weeks or less; 92 were not treated beyond first progression; 13 patients were treated and did not experience progression. The researchers found that 69% of those enrolled (25 patients) who were treated beyond progression experienced subsequent tumor reduction or stabilization in target lesion size. One-third of the patients experienced significant tumor shrinkage of more than 30%; overall survival (OS) rates were markedly better. The OS rate was 22.5 months for patients who continued treatment, in contrast with 12.3 months for those not treated beyond disease progression.

Dr George said the analysis demonstrated that continuing immunotherapy treatment after disease progression is safe and may lead to prolonged survival. “The side effects from nivolumab when continued beyond progression were not different from the reported adverse events from phase 2 or phase 3 trials,” Dr George told Cancer Therapy Advisor. “There could be unconventional type of responses. The disease could look worse radiographically, despite a potential for clinical and survival benefit from nivolumab.”

The researchers suggest 2 hypotheses to explain these observations: it may be that increased tumor size could be the result of the infiltration of immune cells and subsequent inflammation of the tumor, or that the growth of the pre-existing tumor may be the result of a delay in the immune response.

RELATED: More Renal Cell Carcinoma Patients Receiving Treatment

Renal oncologist James Brugarolas, MD, PhD, associate professor in the Department of Internal Medicine’s Division of Hematology/Oncology and the Department of Developmental Biology at the University of Texas Southwestern Medical Center in Dallas, said this study shows that nivolumab may be continued in some patients who are tolerating the drug well and that extension of the therapy could lead to significantly better outcomes. He said the study findings are clinically significant and, if confirmed, could change the standard of care.

“The findings are consistent with results in other tumor types, suggesting that some patients may benefit from treatment beyond what may appear as tumor progression. The challenge is in the identification of those patients who could benefit from continued therapy,” Dr Brugarolas told Cancer Therapy Advisor.

The authors report that larger prospective clinical studies of nivolumab treatment beyond RECIST-defined first progression in patients with metastatic RCC are warranted. They hope that additional data will lead to the development of guidelines to help ensure optimal use of immunotherapy in patients with metastatic RCC.


1. George S, Motzer RJ, Hammers HJ, Redman BG, Kuzel TM, Tykodi SS, et al. Safety and efficacy of nivolumab in patients with metastatic renal cell carcinoma treated beyond progression: a subgroup analysis of a randomized clinical trial [published online ahead of print May 12, 2016]. JAMA Oncol. doi: 10.1001/jamaoncol.2016.0775.