Nivolumab Plus Ipilimumab Trends Toward Prolonged OS in nccRCC
Nivolumab plus ipilimumab showed a strong median overall survival (OS) advantage at 12 months and a trend toward overall prolonged OS vs SOC in non-clear cell renal cell carcinoma.
Renal cell carcinoma: © dr microbe - stock.adobe.com
The dual-immunotherapy combination of nivolumab (Opdivo) and ipilimumab (Yervoy) showed a strong clinical benefit at 12 months with a trend toward prolongation of overall survival (OS) vs standard of care (SOC) in patients with advanced or metastatic non-clear cell renal cell carcinoma (nccRCC), according to findings from the phase 2 SUNNIFORECAST study published in the Annals of Oncology.1
At a median follow-up of 21.5 months (range, 0.0 -70.2), the median OS was 33.2 months with nivolumab/ipilimumab compared with 25.2 months with SOC (HR 0.81, 95% CI, 0.61-1.099; P = 0.163). The 12-month OS rates were 78% vs 68%, respectively (P = .026). The objective response rate (ORR) was 32.8% vs 19.3%, respectively. Unlike OS, median progression-free survival (PFS) did not vary much between arms at 5.4 months vs 5.7 months, respectively (HR, 0.99; 95% CI, 0.77-1.28).
Across all efficacy end points, there were no major differences observed between papillary and non-papillary subtypes of RCC. Also of note, PD-L1 positivity was associated with a much stronger OS advantage for the combination arm vs SOC (HR, 0.56; 95% CI, 0.37-0.86).
The safety population included 299 patients. Across all grades, treatment-related adverse events occurred in 87% of the immunotherapy combination arm and 96% of the SOC arm. The rates of serious adverse events were 48% vs 39%, respectively. Twenty-seven (17%) patients and 13 (9%) patients, respectively, had to discontinue treatment due to treatment-related toxicity.
“This is the first prospective randomized trial which compared dual checkpoint inhibitor combination therapy with the actual SOC in nccRCC,” first study author Lothar Bergmann, MD, deputy medical director in the Department of Internal Medicine at J.W. Goethe University in Frankfurt, Germany, said when discussing similar data from the study at the 2024 ESMO Congress.2 “The randomized SUNNIFORECAST trial underlines a relevant clinical benefit of the combination [of ipilimumab and nivolumab] in nccRCC and may be a new standard in these entities. Further data in the study of these rare diseases are needed in the future.”
Study Design and Schema
The European, multi-center, investigator-initiated open-label phase 2 SUNNIFORECAST study randomized 309 patients with previously untreated advanced or metastatic nccRCC in a 1:1 ratio to nivolumab/ipilimumab (n = 157) or SOC (n = 152). Per the study design, SOC was investigator’s choice of any approved standard treatment. SOC in this setting often comprises tyrosine kinase inhibitors (TKIs) alone or combined with an immune checkpoint inhibitors.
Patient characteristics were well balanced between the 2 arms. Across all patients, the median age was 62 years (range ,19-86) and 71% of patients were male. IMDC prognostic risk scores were favorable (24%), intermediate (52%), and poor (24%). Seventy-seven percent of patients had prior surgery and 9% had prior radiotherapy.
Patients assigned to the dual immunotherapy arm received 3 mg/kg of nivolumab plus 1 mg/kg of ipilimumab every 3 weeks for a total of 4 doses. Nivolumab was then administered at a fixed dose of 240 mg every 2 weeks or 480 mg every 4 weeks.
OS at 12 months was the primary end point. Secondary end points were median OS, ORR, PFS, safety, and quality of life.
"In conclusion, the randomized SUNNIFORECAST trial underlines a potential clinical benefit of ipilimumab/nivolumab in nccRCC,” Bergmann et al wrote in their published manuscript.1 “Whether a TKI [combined with an immune checkpoint inhibitor] has a similar efficacy [as dual immune checkpoint inhibitor therapy] has to be clarified by further randomized trials. Due to the rarity of different nccRCC entities, international cooperations will be essential."
