Clinical trial findings presented at European Society for Medical Oncology (ESMO) 2017 Congress in Madrid, Spain, could signal a major shift in the front-line treatment of metastatic renal cell carcinoma (mRCC).

The CheckMate-214 trial demonstrated that combined immunotherapy with the checkpoint inhibitors nivolumab and ipilimumab results in superior outcomes—including significantly better objective response rate (ORR), progression-free survival (PFS), and overall survival (OS)—compared with sunitinib among patients with previously untreated intermediate- and poor-risk mRCC. Sunitinib is the current standard of care for this patient population. Bernard Escudier, MD, of Institut Gustave Roussy, Villejuif, France, who presented the study’s findings, said nivolumab/ipilimumab will rapidly become the new standard of care for the front-line treatment of these patients.

The trial included 1096 patients randomly assigned to receive nivolumab/ipilimumab (550 patients) or sunitinib (546 patients). With a minimum follow-up of about 17.5 months, the ORR was 41.6% in the nivolumab/ipilimumab arm compared with 26.5% among sunitinib recipients among patients with intermediate- and poor-risk disease. In addition, 9.4% of patients in the combination therapy arm achieved a complete response compared with 1.2% of patients in the sunitinib arm. Median PFS was 11.6 months in the immunotherapy arm compared with 8.4% in the sunitinib arm. Compared with sunitinib, the nivolumab/ipilimumab combination decreased the risk of disease progression by a significant 18%.

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The beneficial effect of nivolumab/ipilimumab over sunitinib was more pronounced among intermediate- and poor-risk patients having baseline PD-L1 expression of 1% or greater. In these patients, the ORR was 58% in the combination arm versus 25% among sunitinib recipients, and the median PFS was 22.8 months versus 5.9 months. The combination therapy decreased the risk of disease progression by 52% compared with sunitinib.

Of the 550 patients treated with nivolumab/ipilimumab, 159 (28.9%) died during follow-up compared with 202 (36.9%) of the 546 sunitinib recipients, Dr Escudier’s group reported. Among intermediate- and poor-risk patients, median OS was 26 months in the sunitinib group and not yet reached in the combination arm. Among patients in all risk groups, median OS was 32.9 months among sunitinib recipients and not yet reached in the combination arm.

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Moshe Ornstein, MD, a genitourinary oncologist at the Cleveland Clinic Taussig Cancer Institute, who was not part of the Checkmate-214 research team, noted that the results of the study presented at the ESMO congress “represent the first phase 3 data to support the use of checkpoint inhibitors in the front-line setting for metastatic renal cell carcinoma.”

“The superior objective response rates and overall survival of combined ipilimumab and nivolumab compared to sunitinib in patients with intermediate- and poor-risk mRCC will likely usher in an era in which this combination of checkpoint inhibitors become the standard of care for front-line mRCC,” Dr Ornstein told Renal & Urology News.

The ORR and OS rates also favored the nivolumab/ipilimumab combination in the intention-to-treat population (patients with favorable-, intermediate-, and poor-risk disease), suggesting that this combination also may become a new standard of care as front-line mRCC treatment for all patients, regardless of risk group.

A primary concern of the nivolumab/ipilimumab combination is the perceived toxicity, Dr Ornstein said. Although the combination was very well tolerated overall, 25% of patients who received the treatment discontinued it because of drug toxicity compared with only 12% of sunitinib-treated patients. He pointed out, however, that 79% of the patients in the ipilimumab/nivolumab arm successfully received all 4 doses of ipilimumab as called for in the trial protocol.



Escudier B, Tannir N, McDermott D, et al. CheckMate 214: Efficacy and safety of nivolumab + ipilimumab (N+I) v sunitinib (S) for treatment-naïve advanced or metastatic renal cell carcinoma (mRCC), including IMDC risk and PD-L1 expression subgroups. LBA5. Presented at the European Society for Medical Oncology 2017 congress in Madrid, Spain.