Nivolumab/ipilimumab prolongs treatment-free survival with and without toxicity in patients with untreated advanced renal cell carcinoma (RCC), according to an updated analysis of the phase 3 CheckMate 214 trial presented at the European Society for Medical Oncology (ESMO) Virtual Congress 2020.
"Conventional measures may not fully characterize the impact of immuno-oncology agents," comment the investigators in their presentation abstract, led by first author Meredith Regan, ScD, Associate Professor of Medicine at Harvard Medical School. "Previous analyses, including of CheckMate 214 data (minimum follow-up, 30 months), have shown that patients discontinuing immuno-oncology regimens may experience periods of disease control without subsequent anticancer therapy but may still experience toxicity. Treatment-free survival with and without toxicity can simultaneously characterize disease control and toxicity for this off-treatment period."
In CheckMate 214, 1,096 adults with advanced, predominantly clear cell RCC were randomized in a 1:1 ratio to receive nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every three weeks, for a total of four doses, followed by nivolumab 3 mg/kg every two weeks; or sunitinib 50 mg once daily for four weeks. The primary end point of the analysis, which included all patients enrolled in the trial, was treatment-free survival, defined as the area between Kaplan-Meier curves for time to protocol therapy cessation and time to subsequent systemic therapy or death. Treatment-free survival was subdivided into days with and without toxicity, which was defined as the reporting of at least one grade 3 or higher treatment-related adverse event.
At a minimum follow-up of 42 months, a higher proportion of patients receiving nivolumab/ipilimumab were alive (56% vs 47%), remained on original therapy (13% vs 7%), and were surviving without subsequent therapy (31% vs 12%) compared with those receiving sunitinib. Patients receiving nivolumab/ipilimumab experienced a longer 42-month restricted mean treatment-free survival compared with sunitinib (7.8 vs 3.3 months), as well as longer treatment-free survival without toxicity (7.1 vs 3.0 months). For patients with intermediate/poor risk according to the International Metastatic RCC Database Consortium (IMDC), mean treatment-free survival was more than twice as long in the nivolumab/ipilimumab arm compared with the sunitinib arm (6.9 vs 3.1 months) and was nearly three times as long for patients with favorable risk (11.0 vs 3.7 months).
"Nivolumab/ipilimumab provides longer survival versus sunitinib," conclude Dr. Regan and colleagues. "Regardless of IMDC risk group, patients on nivolumab/ipilimumab spent greater survival time treatment-free without toxicity compared with sunitinib."
For More Information
Regan M, Jegede OA, Mantia C, et al (2020). Treatment-free survival, with and without toxicity, after immuno-oncology vs targeted therapy for advanced renal cell carcinoma (aRCC): 42-month results of CheckMate 214. Ann Oncol (ESMO Virtual Congress Abstracts), 31(suppl_4):S550-S550. Abstract 713P. DOI:10.1016/annonc/annonc274
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