Kidney Cancer Patients Given an Immunotherapy Combination Have More Time Without Treatment Than Those Given a Targeted Therapy, a Study Shows

“Patient-centered” study seeks to assess quality of time that patients live by measuring the “treatment-free survival” outcome.

A treatment combining two immunotherapies gave patients with advanced kidney cancer a longer time without subsequent treatment than those who received a targeted therapy, according to clinical trial data published in Clinical Cancer Research, a journal of the American Association for Cancer Research. 

Treatment-free survival (TFS) is defined by the study author Meredith Regan, ScD, associate professor at Harvard Medical School and Dana-Farber Cancer Institute, as the time between ending the therapy assigned to the patient as part of the clinical trial and starting a subsequent therapy, or death. 

“This analysis is very patient-centered, and the implications of this work are that we have a new way to assess the value of new treatments to patients when we do clinical trials,” said Regan. 

Depending on their risk level, patients who received a combination of the checkpoint inhibitors nivolumab (Opdivo) plus ipilimumab (Yervoy) had two or three times longer, “treatment-free survival” – without follow-up treatment –   than those who received the targeted therapy sunitinib (Sutent), the authors of the study reported.  

“One of the great challenges in conducting clinical trials is that some of the endpoints we’ve been using to measure the efficacy and value of a treatment are not optimal, especially when evaluating immuno-oncology-based therapy regimens,” said Regan.  

She and her collaborators recently proposed the new TFS outcome to incorporate the quality of survival time into the trial analysis to better inform clinical decision-making.  

“As we continue to develop new treatments, we have an opportunity to think about new methods to better balance the efficacy and toxicity to the patients,” added Regan. “To do that, we needed a new endpoint to quantify those two aspects together—to continue to improve survival for patients while also focusing on how they are spending their time. That’s how TFS came to be.” 

In this study, the researchers evaluated TFS in the CheckMate-214 phase III trial. Results of this trial showed a significantly longer overall survival with the nivolumab and ipilimumab combination (nivolumab + ipilimumab) than with sunitinib in patients receiving their first therapy for advanced renal cell carcinoma, the most common type of kidney cancer. Patients were included who had both intermediate and poor prognostic risk and favorable risk. At 42 months since initiating therapy, 52 percent and 39 percent of patients with intermediate and poor risk were alive with nivolumab + ipilimumab and sunitinib, respectively.  

The TFS analysis was performed for the 42-month time period and included all patients (550 who received nivolumab + ipilimumab and 546 who received sunitinib). TFS was subdivided into treatment-free survival with and without toxicity by counting the days in which patients experienced moderate and severe treatment-related adverse events (TRAEs). 

According to this analysis, over the 42-month period, the mean TFS was more than twice as long after nivolumab + ipilimumab than sunitinib for patients with intermediate/poor risk (6.9 months and 3.1 months, respectively), and three times as long for patients with favorable risk (11.0 months and 3.7 months, respectively).