Only 12% of kidney cancer patients with advanced disease survive five years after their initial treatment. In a Roswell Park Cancer Institute-led study, scientists report that some patients with advanced kidney cancer who continued to receive a novel immunotherapy drug after their disease progressed saw clinical benefit. The research was published online ahead of print in JAMA Oncology, a journal of the American Medical Association.
The study investigated the checkpoint inhibitor nivolumab (brand name Opdivo) in the treatment of 168 patients with advanced kidney cancer in a blinded, randomized, multicenter phase II dose-ranging clinical trial conducted at academic centers in the U.S., Canada, Finland and Italy.
“The analysis from this study demonstrated that continuing the immunotherapy treatment after disease progression is safe and may lead to prolonged survival in this group of patients,” said Saby George, MD, FACP, Associate Professor of Oncology in the Department of Medicine at Roswell Park, first author on the paper. “This study demonstrates the need to develop a greater understanding of how newer immunotherapies work and the optimal use of these medications.”
Treatment with immunotherapy agents such as nivolumab has sometimes been associated with “tumor flare,” a phenomenon in which a tumor gets worse before it shrinks. Per the protocol, treatment continued beyond the first evidence of disease progression in some patients who continue to tolerate the drug and exhibited investigator-assessed clinical benefit. With continued therapy, nearly two-thirds of the patients benefitted in terms of some tumor shrinkage, and one-third of the patients experienced significant tumor shrinkage of more than 30%. Most importantly, overall survival was better: 22.5 months among patients who continued treatment, compared to 12.3 months for those not treated beyond disease progression.
The scientists offer two hypotheses to explain these observations. First, increased tumor size, as measured by imaging, could be the result of the infiltration of immune cells and subsequent inflammation of the tumor. A second explanation is that the growth of the pre-existing tumor may be the result of a delay in the immune response.
“These findings demonstrate that the newer immunotherapy and checkpoint inhibitor drugs such as nivolumab bring new challenges in making treatment decisions based on traditional tumor-assessing methods. Criteria need to be developed that take into account an immune-related response. Additional data may aid in the development of guidelines to help ensure optimal use of this new class of immunotherapy,” says Brian Rini, MD, Professor of Medicine at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, the paper’s senior author.
The research was funded by Bristol-Myers Squibb, manufacturer of nivolumab.
Article: Safety and Efficacy of Nivolumab in Patients with Metastatic Renal Cell Carcinoma Treated Beyond Progression: a Subgroup Analysis of a Randomized Clinical Trial, Saby George, MD; Robert J. Motzer, MD; Hans J. Hammers, MD, PhD; Bruce G. Redman, DO; Timothy M. Kuzel, MD; Scott S. Tykodi, MD, PhD; Elizabeth R. Plimack, MD, MS; Joel Jiang, PhD; Ian M. Waxman, MD; Brian I. Rini, MD, JAMA Oncology, doi:10.1001/jamaoncol.2016.0775, published online 12 May 2016.