Immunotherapy combo improves OS vs sunitinib in intermediate/poor-risk advanced RCC
Nivolumab plus ipilimumab significantly improves overall survival (OS) vs sunitinib in patients with intermediate- or poor-risk advanced renal cell carcinoma (RCC), according to results of the first-line CheckMate 214 study presented at the European Society for Medical Oncology (ESMO) 2017 Congress held in Madrid, Spain.
“The study met its coprimary endpoints of objective response rate [ORR], progression-free survival [PFS] and OS in patients with intermediate- or poor-risk disease stratified by the International Metastatic Renal Cell Carcinoma Database Consortium [IMDC] prognostic score,” said investigator Professor Bernard Escudier of the Institut Gustave Roussy in Villejuif, France. [ESMO 2014, abstract LBA5]
The phase III study included 1,082 patients with treatment-naïve advanced or metastatic RCC. The patients were randomized to receive nivolumab 3 mg/kg plus ipilimumab 1 mg/kg Q3W for four doses followed by nivolumab 3 mg/kg Q2W (n=547), or sunitinib 50 mg once daily for 4 weeks (n=535).
“In patients with IMDC intermediate- or poor-risk disease, ORR was 42 percent in the immunotherapy arm vs 27 percent in the sunitinib arm [p<0.0001]. Complete response [CR] was achieved in nine vs one patient,” Escudier reported. “The median duration of response was not yet reached in the immunotherapy arm vs 18.2 months in the sunitinib arm. At the time of data analysis, 72 patients in the immunotherapy arm and 63 in the sunitinib arm had ongoing responses.”
“Median OS was not reached in the immunotherapy arm vs 26 months in the sunitinib arm [hazard ratio (HR), 0.63; p<0.0001] in patients with IMDC intermediate- or poor-risk disease, while median PFS was 11.6 vs 8.4 months [HR, 0.82; p=0.0331],” he continued.
In the intention-to-treat (ITT) population, confirmed ORR was 39 vs 32 percent for immunotherapy vs sunitinib (p=0.0191), median OS was not reached vs 32.9 months (HR, 0.68; p=0.0003), and median PFS was 12.4 vs 12.3 months (HR, 0.98; p=0.8498).
In exploratory analyses, patients with tumour PD-L1 levels ≥1 percent achieved higher ORR (53–58 percent vs 22 percent; p<0.0001) and longer PFS (22.8 vs 5.9 months; HR, 0.48; p=0.0003) with nivolumab plus ipilimumab vs sunitinib. In those with PD-L1 levels <1 percent, differences in ORR (36–37 vs 28–35 percent) and PFS (11 vs 10.4 months; HR, 1.00; p=0.967) were less significant.
“Interestingly, patients with favourable-risk disease fared better with sunitinib. In these patients, ORR was 52 percent with sunitinib vs 29 percent with immunotherapy, while median PFS was 25.1 vs 15.3 months [HR, 2.18; p<0.00001,” Escudier noted.
The safety profile of nivolumab plus ipilimumab was manageable and consistent with previous studies. Grade 3–5 treatment-related adverse events (AEs) occurred in 46 percent of patients in the immunotherapy arm vs 63 percent of patients in the sunitinib arm. These events led to treatment discontinuation in 15 vs 7 percent of patients.
“Our results support the use of nivolumab plus ipilimumab as a new first-line standard of care option for patients with advanced RCC,” Escudier concluded.
“These results represent a paradigm change in first-line management of metastatic RCC as sunitinib has never been defeated by any other agent in a randomized phase III superiority trial before. The ORR, response duration and CR rate achieved with nivolumab plus ipilimumab are the highest ever reported in this patient population,” said discussant Dr Manuela Schmidinger of the Medical University of Vienna, Austria.
“Once we can properly address the biology of a patient’s tumour, we may be able to pick out the best individual treatment among various first-line options. Some of the tyrosine kinase inhibitor/immune checkpoint inhibitor combinations currently evaluated in phase III trials will likely become standard of care options,” she noted.