Practice-Changing: Nivolumab plus Ipilimumab Beat Sunitinib as First-Line Treatment for Metastatic RCC

Madrid, Spain—The combination of nivolumab (Opdivo) plus ipilimu­mab (Yervoy) improved overall response rates (ORRs), progression-free survival (PFS), and overall survival (OS) in patients with intermediate- and poor-risk metastatic renal-cell carcinoma (RCC) compared with sunitinib in the CheckMate-214 study. These results were presented at the 2017 European Society for Medical Oncology Congress.

“This study supports the use of nivolumab plus ipilimumab as a new first-line option,” stated lead investigator Bernard Escudier, MD, Chairman, Renal Cancer, Institut Gustave Roussy, Villejuif Cedex, France, who presented the results. An exploratory analysis suggested that sunitinib was more effective than the immunotherapy combination in patients with favorable-risk disease.

The CheckMate-214 study enrolled 1096 newly diagnosed patients with advanced or metastatic RCC. Patients were randomized in a 1:1 ratio to nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 2 weeks or to sunitinib 50 mg daily for 4 weeks, then 2 weeks off treatment (a 6-weeks cycle). Treatment was continued until disease progression or unacceptable toxicity.

Among patients with intermediate- and poor-risk disease, 425 were randomized to combination immunotherapy and 422 to sunitinib. The median age was approximately 62 years, and 79% of patients were intermediate-risk. Approximately 22% of the patients had PD-L1–positive expression. In the intent-to-treat analysis, 23% of patients were good risk; 80% had more than 2 metastases.

At a median follow-up of 25.2 months in the intermediate- and poor-risk group, the ORR was 42% for the immunotherapy combination group versus 27% for sunitinib (P <.0001). Complete response (CR) rates were 9% with the combination versus 1% in the sunitinib arm.

Duration of response was not yet reached in the combination immunotherapy arm versus 18.2 months for sunitinib. Overall, 72% of patients have had an ongoing response to the combination immunotherapy.

The median PFS was 11.6 months in the combination arm versus 8.4 months with sunitinib (P = .0331), which did not meet the prespecified P value for statistical significance.

“This difference in PFS is clinically meaningful in my view,” Dr Escudier told the audience. The OS was also significantly improved with the combination immunotherapy. The median OS was not reached in the combination arm versus 26 months in the sunitinib arm—a 37% risk reduction for death (P <.0001).

In intermediate- and poor-risk patients, PD-L1 expression was associated with a better response and longer PFS with immunotherapy, but patients with PD-L1–negative disease also benefited.

“Toxicity [of nivolumab and ipilim­umab] was manageable and consistent with previous studies,” Dr Escudier told the audience.

Nivolumab is approved by the FDA for previously treated metastatic RCC, but not as first-line treatment.

These results are practice-changing, according to Manuela Schmid­inger, MD, Medical University of Vienna, Austria. “So far, sunitinib has never been defeated by another treatment. Sunitinib is a brave comparator. Nivolumab and ipilimumab can be considered a new standard of care because of the survival benefit. The response rate is one of the highest seen in advanced RCC, and the CR rate is the highest ever seen,” Dr Schmidinger stated.

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