(UroToday.com) The European Society of Medical Oncology (ESMO) 2021 virtual annual meeting’s non-prostate cancer session included a presentation by Dr. Robert Motzer discussing updated data from the CheckMate 214 trial with 5-years of follow-up. The combination of nivolumab + ipilimumab is approved by the European Commission and the US FDA for first-line treatment of patients with advanced RCC with IMDC intermediate/poor risk disease, based on superior overall survival (OS) and objective response rate (ORR) over sunitinib in the randomized, phase 3 CheckMate 214 trial.1 Conditional survival, used to predict sustained treatment benefit, accounts for time since treatment initiation and provides improved prognostic information at landmark time points. Conditional survival in advanced RCC patients was estimated in CheckMate 214 with a minimum 5-years of follow-up (median follow-up, 67.7 months).
Patients with clear cell advanced RCC were randomized to nivolumab 3 mg/kg + ipilimumab 1 mg/kg Q3W×4 then nivolumab 3 mg/kg Q2W versus sunitinib 50 mg QD for 4 weeks on, 2 weeks off. Trial endpoints included OS, progression-free survival (PFS) and ORR (both per independent radiology review using RECIST v1.1) in IMDC intermediate/poor risk (primary), intent-to-treat (secondary), and favorable risk (exploratory) patients. Conditional survival—the probability of remaining alive (cOS), progression-free (cPFS), or in response (cDOR) 2 years beyond landmark time points of 2 years and 3 years—was analyzed.
Overall, 1,096 patients were randomized to nivolumab + ipilimumab (n=550) or sunitinib (n=546). There were 34 patients (6%) of 547 treatment patients in the nivolumab + ipilimumab arm and 9 (2%) of 535 treated patients in the sunitinib arm continued therapy at five years of follow-up. Superior OS with nivolumab + ipilimumab versus sunitinib was maintained in the intention-to-treat (HR 0.72) and intermediate/poor risk (HR 0.68) patients:
Five-year PFS probabilities with nivolumab + ipilimumab versus sunitinib were 30% versus 14% (intention-to-treat) and 31% versus 11% (intermediate/poor risk). As follows is the PFS curve in the intention-to-treat cohort:
ORR was 39% (95% CI 35-44%) with nivolumab + ipilimumab versus 32% (95% CI 29-37%) with sunitinib in the intention-to-treat patients and 42% (95% CI 37-47%) versus 27% (95% CI 23-31%) in intermediate/poor risk patients.
Consistently higher cOS, cPFS, and cDOR rates were observed with nivolumab + ipilimumab versus sunitinib in intent-to-treat and intermediate/poor risk patients at all time points.
In the nivolumab + ipilimumab arm, the probability of remaining alive 2 years beyond the 3-years landmark (cOS) was 81% (intent-to-treat), 79% (intermediate/poor risk), and 85% (favorable risk). The probability of remaining progression-free (cPFS) for an additional 2 years beyond the 3-years landmark was 89% (intent-to-treat), 90% (intermediate/poor risk), and 85% (favorable risk). For nivolumab + ipilimumab patients who were in response at 3 years, the probability of remaining in response (cDOR) for an additional 2 years was 89% (intent-to-treat), 90% (intermediate/poor risk), and 85% (favorable risk). There were no new safety signals that emerged with longer follow-up.
Dr. Motzer concluded his presentation of updated results from the CheckMate 214 trial with the following take-home messages:
- In the longest phase 3 follow-up for a checkpoint inhibitor combination therapy in advanced RCC together with the first conditional survival analyses of patients in the CheckMate 2014 trial, nivolumab + ipilimumab demonstrated durable survival and response benefits versus sunitinib in all patients
- Patients who were alive, progression free, or in response 3 years after time zero had a greater probability of remaining so at year 5 with nivolumab + ipilimumab versus sunitinib
- Conditional OS, PFS, and response estimated for intention-to-treat patients improved from time zero to 3 yeas for survivors of advanced RCC in the nivolumab + ipilimumab arm, providing meaningful quantitative prognostic information for patients and clinicians
- The overall incidence of treatment-related adverse events in the nivolumab + ipilimumab arm remained consistent with previous reports and the incidence of grade 3-4 treatment related adverse events remained lower with nivolumab + ipilimumab versus sunitinib with extended follow-up
- Taken together, these results highlight the durable clinical benefits observed with nivolumab + ipilimumab versus sunitinib in patients with advanced RCC after 5 years of follow-up and show that most patients alive or in response at the 3-year landmark will remain alive or in response at 5 years with nivolumab + ipilimumab
Presented by: Robert J. Motzer, MD, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2021 European Society for Medical Oncology (ESMO) Annual Congress 2021, Thursday, Sep 16, 2021 – Tuesday, Sep 21, 2021.
- Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med 2018;378(14):1277-1290.