A phase III study by Dr. Robert Motzer and colleagues in NEJM found significantly higher OS and ORRs with the immunotherapy combination.
A randomized phase III study published in the New England Journal of Medicine suggests that it is time to change the standard of care for intermediate- and poor-risk patients with renal cell carcinoma (RCC). The results showed overall survival (OS) and objective response rates (ORRs) were significantly higher in patients who received combination immunotherapy with nivolumab plus ipilimumab, compared with those who received the tyrosine kinase inhibitor (TKI) sunitinib.
“The study represents a change in treatment paradigm for first-line RCC away from the TKI sunitinib, which has been standard of care for the past 10 years, to immunotherapy with nivolumab plus ipilimumab. The benefits include higher response rate; complete responses; and, most notably, improved overall survival,” said lead study author and principal investigator Robert Motzer, MD, from Memorial Sloan Kettering Cancer Center, in New York City.
In the phase III trial, 1,096 RCC patients who had received no prior treatment were randomly assigned to treatment at 175 sites in 28 countries. A total of 550 patients were treated with the nivolumab-plus-ipilimumab combination, and 546 received sunitinib. The researchers found that, at a median follow-up of 25.2 months, in intermediate- and poor-risk patients, the 18-month OS rate was 75% in the nivolumab-plus-ipilimumab arm and 60% in the sunitinib arm.
The study showed that the median OS rate was not reached in the nivolumab-plus-ipilimumab arm vs 26.0 months in the sunitinib arm (hazard ratio for death, 0.63; P < .001). The ORRs were 42% in the combination arm vs 27% in the sunitinib arm (P < .001). The researchers found that the complete response rates were 9% vs 1% in the sunitinib arm. The median progression-free survival was 11.6 months in the combination arm vs 8.4 months in the sunitinib arm.
“The study follows with the emerging role of immunotherapy in advanced RCC, starting with single-agent nivolumab in pretreated patients and now to this impressive combination regimen. Of note, however, is the toxicity of the combination program which needs to be recognized and managed, but overall the benefit outweighs the risk,” Dr. Motzer and colleagues wrote. “This will be a new standard of care in patients with intermediate/poor risk advanced RCC.”
Treatment-related adverse events occurred in 93% of patients in the nivolumab-plus-ipilimumab arm and in 97% of patients in the sunitinib arm. Grade 3 or 4 events occurred in 46% of patients in the combination arm and 63% in the sunitinib arm. Treatment-related adverse events leading to discontinuation occurred in 22% of the patients in the combination arm and 12% of patients in the sunitinib arm.
“We are now conducting a large phase III trial comparing nivolumab plus ipilimumab to placebo in patients with localized kidney cancer and resection of all disease by nephrectomy, ie, the adjuvant setting. This trial is actively enrolling patients globally,” Dr. Motzer and colleagues wrote.