medwireNews: Time spent off treatment could be used as a novel clinical trial endpoint for patients undergoing renal cell carcinoma (RCC) immunotherapy, suggest study findings reported at the ESMO Congress 2019 in Barcelona, Spain.
“Patients discontinuing cancer treatment may experience periods of disease control without needing subsequent systemic anticancer therapy, as well as persistent or new-onset toxicity after therapy discontinuation,” explained Meredith Regan (Harvard Medical School, Boston, Massachusetts) and co-workers in a poster presentation.
The researchers explored treatment-free survival using data from 1082 participants in the phase III CheckMate 214 trial which showed that nivolumab plus ipilimumab achieved significantly longer overall survival than sunitinib for treatment-naïve advanced RCC.
The team produced Kaplan-Meier curves of the time to event endpoints and defined TFS as the area between the time to protocol drug cessation curve and the time to subsequent therapy or death curve, with a further division created between time with and without toxicity curves.
The 36-month restricted means TFS was 6.8 months with nivolumab plus ipilimumab versus 2.9 months with sunitinib.
The combination arm had more time with grade 3 or more severe treatment-related adverse events (TRAEs) than the sunitinib arm, at 0.4 versus 0.2 months. Nevertheless, TFS without toxicity was longer with nivolumab plus ipilimumab than sunitinib for time without both grade 3 and more severe (6.4 vs 2.8 months) and grade 2 or more severe (4.8 vs 1.6 months) TRAEs.
When the 839 patients with an intermediate or poor IMDC prognostic risk were assessed separately, TFS without toxicity was also higher with nivolumab plus ipilimumab than sunitinib using both the TRAEs grade 3 (5.5 vs 2.8 months) and grade 2 (4.1 vs 1.5 months) cutoffs.
And this was also true for the smaller subgroup of patients with a favorable IMDC prognostic risk, with TFS without TRAEs for the combination arm at the grade 3 (9.4 vs 2.6 months) and grade 2 (6.9 vs 1.8 months) thresholds.
“Among favorable-risk patients, while overall survival was similar, [sunitinib-treated] patients spent greater time on protocol treatment with toxicity whereas [nivolumab plus ipilimumab-treated] patients spent greater time treatment-free without toxicity”, the researchers report.
Indeed, 92% of the sunitinib-treated patients’ overall survival during the 36-month follow-up was spent on the study drug (20.0 months) or subsequent treatment (10.2 months), they say.
The team concluded: “Given the durability of [immunotherapy] responses relative to [sunitinib] after therapy cessation, it is of interest to re-estimate TFS over a longer follow-up of time.”
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This independent news article was supported by an educational grant from Pfizer and Merck KGaA
ESMO Congress 2019; Barcelona, Spain: 27 September–1 October