Nivolumab/Ipilimumab Combo Extends Treatment-Free Survival in RCC

Meredith M. Regan, ScD

Patients with advanced renal cell carcinoma (RCC) assigned to nivolumab (Opdivo) plus ipilimumab (Yervoy) had a longer treatment-free survival (TFS) than patients treated with sunitinib (Sutent). Furthermore, those patients assigned to the combination spent less time experiencing treatment-related adverse events (TRAEs).

Meredith M. Regan, ScD, an associate professor in the Department of Data Sciences at Dana-Farber Cancer Institute, presented results from an analysis of data collected in the phase III CheckMate 214 trial at the 18th International Kidney Cancer Symposium.¹Immuno-oncology agents have been shown to successfully extend survival in many cancers, so physicians are now able to focus on improving patients’ quality of life, she said.

“When we look at the nivolumab/ipilimumab group versus sunitinib, the treatment-free time is about twice as long,” she said. “If we think about grade 3 toxicities, there is very little time treatment-free with grade 3 or higher treatment-related adverse events.”

TFS is defined as the period between the end of first-line treatment and the start of subsequent therapy.

Patients in the nivolumab/ipilimumab arm received the combination every 3 weeks for up to 4 doses, followed by nivolumab alone every 2 weeks. Patients in the sunitinib arm received the agent once daily for 4 weeks of each 6-week cycle.

Treatment continued until disease progression, unacceptable toxicity, or patient decision.

In the overall population (n = 1082), the combination was associated with a TFS of 6.8 months versus 2.9 months for sunitinib at a median follow-up of 30 months. TFS without TRAEs also favored the combination by 3.6 months for grade ≥ 3 TRAEs and 3.2 months for grade ≥ 2 TRAEs.

Among intermediate- and poor-risk patients, the combination was associated with an improvement of about 2.6 months for TFS without grade ≥ 3 or grade ≥ 2 TRAEs.

Among favorable-risk patients, the combination induced a difference in TFS without toxicities of 6.8 months (9.4 vs 2.6 months) for grade ≥ 3 TRAEs and of 5.2 months (6.9 vs 1.8 months) for grade ≥ 2 TRAEs. At present, the nivolumab/ipilimumab combination is not indicated for this population.

Regan noted that not only did the combination appear to improve TFS, patients also had fewer toxicities during their time off treatment compared with those treated with sunitinib.

“We can really see, especially in this time when patients are alive and doing well, how are they spending their survival time,” she said. “The dream is to treat a patient, get them off treatment, and allow them to go back to their life without having to be treated all the time and without having side effects of treatment.”

She added that TFS could represent a novel end point for clinical trials, which would change clinical trial design and drug development.

The FDA approved the nivolumab/ipilimumab combination in April 2018 based on results from CheckMate 214. Frontline treatment with the combination reduced the risk for death by 32% compared with sunitinib for patients with metastatic RCC. The risk reduction was 37% in patients with intermediate- and poor-risk RCC, who constituted about 75% of the intent-to-treat (ITT) population.

The median overall survival (OS) in the overall population was not reached with the combination versus 32.9 months with sunitinib (HR, 0.68; 99.8% CI, 0.49-0.95;P= .0003). In patients with intermediate- and poor-risk RCC, the median OS was not reached in the nivolumab and ipilimumab arm and was 26.6 months in the sunitinib arm (HR, 0.63; 99.8% CI, 0.44-0.89;P<.0001). There was no benefit for the combination versus sunitinib in those with favorable risk.

Previously, in CheckMate 067/069, TFS for patients receiving nivolumab plus ipilimumab was greater compared with nivolumab or ipilimumab alone, and time with persistent grade &ge;3 TRAEs comprised a small proportion of the TFS period for all treatments.²

References

1. Regan MM, Atkins MB, Powles T, et al. Treatment free-survival, with and without toxicity, as a novel outcome applied to immuno-oncology agents in advanced renal cell carcinoma. Presented at: the 18th International Kidney Cancer Symposium; November 15-16, 2019; Miami, Florida.
2. Regan MM, Werner L, Rao S, et al. Treatment-free survival: a novel outcome measure of the effects of immune checkpoint inhibition-a pooled analysis of patients with advanced melanoma [published online September 9, 2019].J Clin Oncol.doi: 10.1200/JCO.19.00345.