Pre- and Postsurgical Opdivo Does Not Boost Relapse-Free Survival in Kidney Cancer

Adding Opdivo (nivolumab) before and after surgery did not improve recurrence-free survival (RFS; the time patients live without their disease coming back) in patients with high-risk renal cell carcinoma (RCC; kidney cancer), according to research published in The Lancet Oncology.

The phase 3 PROSPER EA8143 trial included patients 819 adults with previously untreated RCC or clear cell RCC that is 7 centimeters or larger and/or spread to the lymph nodes. Half the patients were randomly assigned to receive Opdivo before and after partial or complete nephrectomy (surgical removal of part of or the entire kidney). The other half of the study population was randomly assigned to undergo surgery only, followed by surveillance.

“We were surprised that we didn't see an improvement in treating patients with [Opdivo], even compared to not getting treatment [before and after surgery],” study author, Dr. Naomi B. Haas, director of the Prostate and Kidney Cancer Program at Pen Medicine said in an interview with CURE®. “So we were very surprised about that, especially because there was the study that came out a little bit before that … which was giving a different drug, adjuvant [Keytruda (pembrolizumab)], just in the adjuvant (post-surgical) setting, that did show an improvement in decreasing the relapse of kidney cancer.”

Both Opdivo and Keytruda are types of immunotherapy drugs called checkpoint inhibitors. They target a certain protein or pathway that helps cancer cells hide from the immune system. By stopping the checkpoint, the immune system can then find and attack cancer cells.

READ MORE: FDA Approves Keytruda for Adjuvant Treatment of Kidney Cancer

Haas mentioned that her team is not entirely sure why an earlier study showed benefits with Keytruda, but this one did not show improved outcomes with Opdivo. Perhaps, she said, it has something to do with the patient population.

“We wondered, to some extent, whether there were things in the patient population, just characteristics that were subtly different,” she said. “One difference that makes our studies stand out is that we enrolled all patients who had who were willing to have a biopsy, so they had either clear cell or non-clear cell [disease]. And that was another agreement that we've made with the patient advocacy groups. The other studies that were conducted were all in the adjuvant space, so those patients, we knew a lot more about their cancer.”

Findings from PROSPER EA8143 showed that at a median follow-up of 30.4 months and 30.1 months in the Opdivo and observation groups, respectively, there was no statistically significant difference in RFS rates. This means that the researchers could not say for sure that one protocol was definitely better than the other.

Interestingly, the RFS rate was 33% in both groups.

Patients in the Opdivo group tended to experience a higher percentage of moderate to severe (grade 3 or 4) or fatal (grade 5) side effects. These occurred in 48% of patients in the Opdivo group and 24% in the surgery-only group.

Looking ahead in improving the field of kidney cancer, Haas mentioned that blood tests are being developed that could help predict which patients with kidney cancer have a higher risk of recurrence. New tools are also helping clinicians more accurately decipher between clear cell and non-clear cell RCC, and who would benefit most from therapies like Keytruda.

“Right now, [Keytruda] is approved for all patients with a tumor size that's at least what we call CT2, so greater than 7 centimeters, and also has kind of an angry-looking or high-grade nucleus under the microscope,” Haas said. “I don't know that all of those patients necessarily need to be treated, but because that clinical trial with [Keytruda] has now shown a benefit in overall survival, we need the cooperation of industry to be able to look at that population and other markers to see whether everybody in that group actually needs to be treated.”

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