CheckMate-214 results presented at the European Society of Medical Oncology meeting show improved overall survival in patients with renal cell carcinoma treated with the nivolumab-ipilimumab combination, compared with sunitinib.
Bristol-Myers Squibb announced last week that CheckMate-214 had been stopped early after it displayed superior overall survival (OS) compared with the standard-of-care treatment, sunitinib (Sutent, Pfizer), in treatment-naïve patients or those with metastatic renal cell carcinoma (mRCC). Subsequently, study results presented over the weekend at the European Society for Medical Oncology (ESMO) congress in Madrid, Spain, showed that combining nivolumab with ipilimumab reduced the risk of death by 37%.
The phase 3 randomized, open-label study evaluated ipilimumab (Yervoy)—a cytotoxic T-lymphocyte-associated protein 4 inhibitor—in combination with the programmed death-1 inhibitor nivolumab (Opdivo). The experimental arm was administered 4 doses of 3 mg/kg nivolumab and 1 mg/kg ipilimumab every 3 weeks. This was followed with 3 mg/kg nivolumab every 3 weeks. Patients in the comparator arm received 50 mg daily sunitinib for 4 weeks, which was resumed after a 2-week break. Treatment continued until disease progression or unacceptable toxicities.
The combination treatment achieved an objective response rate of 41.6%, compared with 26.5% for sunitinib. While the median duration of response was 18.2 months, it was not yet achieved in the combination arm. Progression-free survival (PFS) improved 18% in the combination arm (hazard ratio [HR] = 0.82; 99.1% CI, 0.64 to 1.050; P = .0331) but did not achieve the pre-determined statistical significance threshold of .009 compared with sunitinib. Median PFS was 11.6 months in the combination arm (95% CI, 8.71 to 15.51) against 8.4 months in the sunitinib group (95% CI, 7 to 10.8).
Based on a planned interim analysis, an independent Data Monitoring Committee recommended that the trial be stopped early, according to the press release.
The data presented at ESMO on Sunday showed that at 17.5 months follow up, the combination reduced the risk of death by 37% (HR, 0.63; 99.8% CI, 0.44 to 0.89; P <.0001]) compared with sunitinib in interim- and poor-risk patients. While median OS was 26 months for sunitinib (95% CI, 22.1 to NA), it had not been reached for patients in the combination arm. In all randomized patients, the combination reduced the risk of patient death by 32% (HR 0.68; 99.8% CI, 0.49 to 0.95; P = .0003) compared with sunitinib; median OS was 32.9 months for sunitinib and had not been reached for the combination.
“There is an unmet need for additional treatment options in the first line setting that may provide a meaningful survival benefit including more durable, complete responses for patients with advanced renal cell carcinoma," Bernard Escudier, MD, former chair of the genitourinary group of the Institut Gustave Roussy in Villejuif, France, said in a statement. "These results for the combination of nivolumab and ipilimumab are very encouraging in patients with first-line mRCC who have a very poor prognosis."
The rate of grade 3/4 adverse events (AEs) was much lower with the combination (46%), compared with sunitinib (64%); AE-related treatment discontinuation was higher with the combination (22% versus 12% in the sunitinib arm) and the combination also caused more patient deaths (7, versus 4 in the sunitinib arm).