NEW YORK (Reuters Health) - For patients with advanced renal cell carcinoma (aRCC), upfront treatment with two immune-checkpoint inhibitors (nivolumab and ipilimumab) provided longer treatment-free survival (TFS) than treatment with the VEGF inhibitor sunitinib in the CheckMate 214 randomized trial, regardless of prognostic risk group.
TFS has recently been proposed as a new outcome to characterize the antitumor activity and toxicity experienced during the period after ending immune-checkpoint inhibitor (ICI) therapy until starting subsequent therapy or death.
In a report in Clinical Cancer Research, the CheckMate 214 trialists describe TFS with and without toxicity in 550 patients with aRCC treated with nivolumab and ipilimumab and 546 similar patients treated with sunitinib as first-line therapy.
Forty-two months after randomization, 52% of patients with intermediate-/poor-risk aRCC were alive with the ICI combination and 18% were treatment-free; in the sunitinib group, 39% of similar-risk patients were alive and 5% were treatment-free.
Among favorable-risk patients, 70% of patients in the ICI group were alive and 20% were treatment-free; in the sunitinib group, 73% of similar-risk patients were alive and 9% were off treatment.
After accounting for the possibility that toxicity of ICI therapy persisted or arose after discontinuation, ICI therapy provided longer TFS without toxicity, the researchers report.
"We observed clinically meaningful TFS" among patients with aRCC receiving first-line therapy with nivolumab plus ipilimumab, regardless of prognostic risk, say Dr. Meredith Regan with Harvard Medical School and Dana-Farber Cancer Institute in Boston and colleagues.
Over 42 months, mean TFS was more than twice as long after nivolumab plus ipilimumab than sunitinib for intermediate-/poor-risk patients (6.9 vs. 3.1 months) and three times as long for favorable-risk patients (11.0 vs. 3.7 months).
Mean TFS with severe treatment-related adverse events was a small fraction of time for both treatments and both risk groups (0.6 months and 0.3 months after ICI and sunitinib, respectively, for intermediate-/poor-risk patients; 0.9 months and 0.3 months after ICI and sunitinib, respectively, for favorable-risk patients).
"The novel TFS outcome complements overall survival (OS), progression-free survival, and other outcomes that might impact clinical decision-making with an integrated summary of how OS time is spent," the authors write.
"Clinical trials investigating ICI agents should assess TFS to describe quality of survival time for clinical decision-making when initiating therapy," they suggest.
"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," Dr. Regan added in a news release.
"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. 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," she said.
This study received funding from Bristol Myers Squibb and Ono Pharmaceutical Company Ltd. among others. Dr. Regan has financial ties to Bristol Myers Squibb and other drugmakers.
SOURCE: https://bit.ly/3onS64y Clinical Cancer Research, online November 10, 2021.
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