Durable Benefit Observed at 4 Years With Nivolumab Plus Ipilimumab in Advanced RCC

At 4 years of follow-up, nivolumab (Opdivo) and ipilimumab (Yervoy) in combination as first-line therapy of advanced renal cell carcinoma (RCC) demonstrated durable benefit versus sunitinib (Sutent), according to research presented at the 2020 ESMO Virtual Congress.¹

Investigators also reported that a subgroup of patients with 1 or more target kidney lesions experienced kidney tumor reduction and other benefits from the combination treatment.

“Nivolumab plus ipilimumab was the first immunotherapy combination to demonstrate an overall survival advantage over sunitinib in intermediate- and poor-risk patients with advanced renal cell carcinoma,” CheckMate-214 investigator Laurence Albiges, MD, PhD, said in a press release.² “Now, after 4 years, the durable efficacy seen in CheckMate-214 represents important progress towards the aim of changing survival expectations for these patients,” added Albiges, Head of Genitourinary Unit, Gustave Roussy Institute, Villejuif, France.

The randomized, open-label phase 3 CheckMate-214 trial evaluated the combination of nivolumab and ipilimumab versus sunitinib in patients with previously untreated advanced or metastatic RCC.

Patients in the combination group (n = 550) received 3 mg/kg nivolumab plus 1 mg/kg ipilimumab every 3 weeks for 4 doses followed by 3 mg/kg nivolumab every 2 weeks. Patients in the sunitinib group (n = 546) received 50 mg once daily for 4 weeks, followed by 2 weeks off before continuation of treatment. Treatment was given until progression or unacceptable toxic effects.

Primary end points included overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) in an intermediate- to poor-risk patient population. In addition, non-prespecified, post hoc exploratory efficacy analyses were performed in a subgroup of study patients who had not undergone prior nephrectomy and who had 1 or more target kidney lesions.

In intermediate- to poor-risk patients treated with nivolumab/ipilimumab, median OS was 48.1 months, compared with 26.6 months in patients who received sunitinib (HR, 0.65; 95% CI, 0.54-0.78). The 4-year OS rate for the combination treatment and sunitinib groups was 50.0% and 35.8%, respectively. ORR was also higher in patients receiving combination treatment versus sunitinib, with more ongoing responses in intermediate- to poor-risk patients (65% vs 50%, respectively). Median duration of response was not reached in the combination treatment arm and was 19.7 months for sunitinib.

Analysis of patients in the intention-to-treat (ITT) population with 48 months’ follow-up also pointed to the benefits of nivolumab/ipilimumab treatment. Median OS was not reached for all patients in the combination treatment group vs 38.4 months in the sunitinib group (HR, 0.69; 95% CI, 0.59-0.81), with 4-year OS rates of 53.4% and 43.3%, respectively. ORR was higher in patients receiving nivolumab/ipilimumab, with more ongoing responses compared to patients receiving sunitinib (65% vs 52%). Median duration of response was not reached in patients treated with nivolumab/ipilimumab and was 23.7 months in the sunitinib group.

In the subgroup of patients with 1 or more target kidney lesions, ORR was 34% in the nivolumab/ipilimumab group vs 15% in the sunitinib group. A 30% or greater reduction in target kidney lesion(s) was observed in 35% of patients receiving the combination treatment vs 20% in patients receiving sunitinib.

Treatment-related adverse events of any grade occurred in 94% of patients receiving combination treatment and 97.0% of patients receiving sunitinib, and no new safety signals emerged over the longer follow-up.

“We have now evaluated Opdivo plus Yervoy in multi-year phase 3 trials across RCC, melanoma, non-small cell lung cancer, and mesothelioma, and in all of these studies, we have seen improved survival compared to the existing standard of care,” said Nick Botwood, MD, vice president, interim head, Oncology Development, Bristol Myers Squibb, in a press release. “The 4-year results from CheckMate -214 build on our understanding of and leadership in addressing advanced RCC, reinforcing the potential for durable, long-term survival benefits with Opdivo plus Yervoy in the first-line setting. Taken as a whole, these data provide further evidence for the value of distinct but complementary dual checkpoint inhibition in the treatment of advanced cancers.”

_References

_{1. Albiges L, Tannir NM, Burotto M, et al. Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma 711P in CheckMate 214: 4-year follow-up and subgroup analysis of patients without nephrectomy. Presented at: European Society of Medical Oncology virtual congress; September 19-21, 2020. Abstract 711P.}

_{2. Bristol Myers Squibb. Four-year data continue to show superior, long-term survival benefit with Opdivo (nivolumab) plus Yervoy (ipilimumab) in patients with previously untreated advanced or metastatic renal cell carcinoma. Press release. September 17, 2020. Accessed September 18, 2020. https://bit.ly/3mCwhwO.}