The U.S. Food and Drug Administration has approved a combination of Opdivo (nivolumab) and Yervoy (ipilimumab) for previously untreated patients with advanced renal cell carcinoma (RCC), Bristol-Myers Squibb (BMS) announced.
The approval makes the intravenous regimen of Opdivo (3 mg/kg) plus Yervoy (1 mg/kg) the first immuno-oncology combo treatment for intermediate- and poor-risk patients with the kidney cancer in the U.S. BMS is seeking a similar approval in the E.U.
The FDA’s decision was based on results of the open-label Phase 3 CheckMate 214 clinical trial (NCT02231749). It compared the combo’s effectiveness with that of the standard treatment Sutent (sunitinib).
A total of 425 patients received four cycles of Opdivo and Yervoy every three weeks, followed by maintenance therapy with Opdivo alone. Seven-nine percent received all four doses of the combo, then went on Opdivo monotherapy — either 480 mg every four weeks or 240 mg every two weeks. Scientists recommend this dosage until the disease progresses or there is unacceptable toxicity.
Meanwhile, 422 patients received a once-daily dose of 50 mg of Sutent for four weeks, followed by two weeks off the treatment.
Results showed that the combination decreased the risk of patients’ death by 37%, regardless of their PD-L1 expression level. Patients’ objective response rate — defined as the percentage whose tumor shrank — was also higher in the combination arm. The figures were 41.6% versus 26.5%.
Similarly, progression-free survival, which is the length of time during or after treatment without the disease worsening, increased from 8.4 months in the Sutent arm to 11.6 months in the combo arm.
At the time of data analysis, patients on the combo were still responding to treatment, unlike those receiving Sutent, who had an 18-month duration of response.
“Our goal is to provide cancer patients with medicines that have the potential to extend their lives. As the first treatment option to increase overall survival for subgroups of patients with advanced RCC compared to sunitinib (Sutent), the Opdivo plus low-dose Yervoy combination helps deliver on that promise,” Johanna Mercier, head of U.S. Commercial at BMS, said in a press release.
“This approval demonstrates our commitment to bringing Immuno-Oncology treatments that may improve outcomes to a broader range of RCC patients,” she added.
RCC is the most prevalent type of kidney cancer in adults and about twice as common in men as in women. Among patients with advanced RCC, 75% to 80% have one or more risk factors and are considered at intermediate or poor risk. Despite an increasing number of recent treatment advances, patients are still in need of therapies that improve overall survival.
“Physicians treating advanced RCC have had few options to help achieve the goal of improved survival,” said Robert J. Motzer, MD, the study’s lead author and a medical oncologist at Memorial Sloan Kettering Cancer Center. “Data from the CheckMate -214 trial demonstrated superior overall survival with Opdivo + Yervoy, showing the potential for the combination to become a new standard of care for patients with intermediate- and poor-risk advanced RCC.
“Because of these encouraging results, we now have a new treatment option for newly diagnosed advanced RCC patients across PD-L1 expression levels,” Motzer added.
BMS presented results of CheckMate 214 at the European Society for Medical Oncology Congress in September 2017 and the Society for Immunotherapy of Cancer Annual Meeting in November 2017. The study, “Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma,” was also published in the New England Journal of Medicine.
The combo therapy led to fewer serious or life-threatening adverse events –65% versus 76% with Sutent. But it also resulted in higher treatment discontinuation rates – 31% of patients versus 21%.
The most frequent adverse reactions to Opdivo plus Yervoy were fatigue, rash, diarrhea, musculoskeletal pain, itchy skin, and nausea.