(UroToday.com) The 2024 GU ASCO annual meeting featured a renal cell carcinoma session and a presentation by Dr. Nizar Tannir discussing long-term follow-up data from the phase 3 CheckMate 214 trial. First-line nivolumab + ipilimumab has provided substantial long-term survival benefits over sunitinib in patients with advanced renal cell carcinoma (RCC) in CheckMate 214.1-3
At the GU ASCO 2024 annual meeting, Dr. Tannir reported survival, response per independent radiology review committee, and safety after 6 years of minimum (80 month median) follow-up in all randomized patients, by IMDC risk and in patients with overall survival ≥ 6 years (long-term survivors).
Patients with clear cell advanced RCC were randomized 1:1 to nivolumab 3 mg/kg + ipilimumab 1 mg/kg Q3W×4 then nivolumab 3 mg/kg Q2W vs sunitinib 50 mg QD for 4 weeks on, 2 weeks off:
The endpoints included overall survival, progression-free survival, and objective response rate (both per independent radiology review committee using RECIST v1.1) in IMDC intermediate/poor risk (primary), intent-to-treat (ITT; secondary) and favorable risk (exploratory) patients. Exploratory outcomes in long-term survivor patients were assessed post hoc.
Key baseline characteristics by IMDC risk groups were generally similar between treatment arms and consistent with the ITT population:
Overall survival with nivolumab + ipilimumab vs sunitinib remained superior in ITT (HR 0.72, 95% CI 0.62-0.83) and intermediate/poor risk (HR 0.69, 95% CI 0.59-0.81) patients, with overall survival benefits similar between arms in favorable risk patients (HR 0.82, 95% CI 0.60-1.13):
The median progression-free survival was consistent with previous reports, including by independent radiology review committee (HR 0.88, 95% CI 0.75-1.03) and per investigator (HR 0.79, 95% CI 0.69-0.91):
Progression free survival continued to favor nivolumab + ipilimumab in the intermediate/poor risk group (HR 0.73, 95% CI 0.61-0.87) but favored sunitinib in the favorable risk group (HR 1.76, 95% CI 1.25-2.48):
Objective response rate per independent radiology review committee was higher with nivolumab + ipilimumab vs sunitinib, with more ongoing responses in ITT (60% vs 50%) and intermediate/poor risk (60% vs 50%) patients. In favorable risk patients, objective response rate was lower with nivolumab + ipilimumab vs sunitinib, yet more responses were ongoing (59% vs 52%, respectively). The median duration of response was longer and complete response rate was higher with nivolumab + ipilimumab vs sunitinib regardless of IMDC risk.
Overall survival, progression free survival, and objective response rate favored nivolumab + ipilimumab for patients with lung metastases, but not in patients with live or bone metastases:
The incidence of any and grade 3-4 treatment-related adverse events remained largely unchanged. One additional drug-related death occurred with nivolumab + ipilimumab and zero with sunitinib since the previous database lock. In the long-term survivor subgroup (nivolumab + ipilimumab, n = 208; sunitinib, n = 151), objective response rate was higher (66% vs 53%), more patients had a complete response (27% vs 9%) and fewer progressed (4% vs 11%) with nivolumab + ipilimumab vs sunitinib. Additionally, the median duration of response was longer with nivolumab + ipilimumab (n = 137) vs sunitinib (n = 80) among long-term survivors with confirmed response (76 vs 40 months).
Dr. Tannir concluded this presentation discussing long-term follow-up data from the phase 3 CheckMate 214 trial with the following take-home points:
- The hazard ratio for overall survival with nivolumab + ipilimumab versus sunitinib has remained stable for 8 years (99.1 months) of median following in the ITT and intermediate/poor risk patients and has improved over time in favorable risk patients
- Progression free survival probabilities were higher with nivolumab + ipilimumab versus sunitinib in the ITT population and intermediate/poor risk patients, with 90 month progression free survival probabilities ranging from 23-25% in the nivolumab + ipilimumab arm
- Responses to nivolumab + ipilimumab were deep and durable in the overall study population and patients notably improved duration of response, and there were more complete responders with nivolumab + ipilimumab over sunitinib regardless of IMDC risk
- Long term safety with nivolumab + ipilimumab continues to be manageable
- These results represent the longest follow-up in a phase 3 trial of a checkpoint inhibitor combination therapy in first line advanced RCC and continue to support nivolumab + ipilimumab as standard of care
Presented by: Nizar M. Tannir, MD, FACP, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, CA, Thurs, Jan 25 – Sat, Jan 27, 2024.
References:
- 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.
- Motzer RJ, Rini BI, McDermott DF, et al. Nivolumab plus ipilimumab versus sunitinib in first-line treatment for advanced renal cell carcinoma: Extended follow-up of efficacy and safety results from a randomized, controlled, phase 3 trial. Lancet Oncol 2019 Oct;20(10):1370-1385.
- Albiges L, Tannir NM, Burotto M, et al. Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: Extended 4-year follow-up of the phase III CheckMate 214 trial. ESMO Open 2020 Nov;5(6):e001079.