Nivolumab, ipilimumab combination shows durable benefit for advanced kidney cancer
SAN FRANCISCO — The OS and objective response rate benefits of nivolumab and ipilimumab compared with sunitinib persisted long-term among patients with advanced renal cell carcinoma, according to 30-month follow-up of the phase 3 CheckMate 214 trial presented at Genitourinary Cancers Symposium.
“The results from this 30-month follow-up ... are meaningful as they continue to demonstrate that in patients with advanced renal cell carcinoma, a population with considerable unmet treatment needs, there is potential for long-term survival benefits with the combination of nivolumab [Opdivo, Bristol-Myers Squibb] and ipilimumab [Yervoy, Bristol-Myers Squibb],” Nizar M. Tannir, MD, FACP, Ransom Horne Jr. professor for cancer research in the department of genitourinary medical oncology at The University of Texas MD Anderson Cancer Center, said in a press release.
FDA approved the combination of nivolumab and ipilimumab for intermediate- or poor-risk patients with previously untreated advanced renal cell carcinoma based on data from CheckMate 214 after a minimum follow-up of 17.5 months, which showed improved OS (not reached vs. 26 months; HR = 0.63; P < .001), ORR (42% vs. 27%; P < .001) and PFS (11.6 months vs. 8.4 months) over sunitinib.
Tannir and colleagues reported extended follow-up from the study after a minimum of 30 months (median, 32.4 months).
Researchers randomly assigned patients 1:1 to receive 3 mg/kg nivolumab plus 1 mg/kg ipilimumab every 3 weeks for four doses, followed by 3 mg/kg nivolumab every 2 weeks (n = 550), or 50 mg daily sunitinib for 4 weeks on, 2 weeks off (n = 546).
In the intention-to-treat population, median OS remained not reached for the combination vs. 37.9 months (95% CI, 32.2-not estimable) for sunitinib (HR = 0.71; 95% CI, 0.59-0.86). Sixty-four percent of patients assigned the combination achieved 30-month OS compared with 56% of patients assigned sunitinib.
In the International Metastatic RCC Database Consortium intermediate/poor-risk subgroup (combination, n = 425; sunitinib, n = 422), median OS was not reached (95% CI, 35.6-not estimable) and 26.6 months (95% CI, 22.1-33.4) with sunitinib (HR = 0.66; 95% CI, 0.54-0.8).
In the favorable-risk subgroup (combination, n = 125; sunitinib, n = 124), median OS was not reached in either arm and appeared comparable between the groups (HR = 1.22; 95% CI, 0.73-2.04).
Median PFS was 9.7 months in each arm (HR = 0.85; 95% CI, 0.73-0.98), with a 30-month PFS rate of 28% with the combination and 18% with sunitinib.
“In the intention-to-treat population, nivolumab-ipilimumab demonstrated a late benefit in investigator-assessed PFS, with the curve separating after 12 months,” Tannir said during his presentation. “The tails of the curves show at least a 10% separation in favor of nivolumab-ipilimumab, with a plateau of 28% emerging for nivolumab-ipilimumab.”
The combination also showed a late PFS benefit for the intermediate/poor-risk subgroup (30-month PFS, 28% vs. 12%; median PFS, 8.2 months vs. 8.3 months; HR = 0.77; 95% CI, 0.65-0.9). However, median PFS appeared longer with sunitinib in the favorable-risk group, although the difference did not reach statistical significance (median, 13.9 months vs. 19.9 months; HR = 1.23; 95% CI, 0.9-1.69).
ORR was 41% with the combination vs. 34% with sunitinib (P = .0154), with 53% of patients in the combination group experiencing a response for 18 months or longer compared with 39% of patients in the sunitinib group. Fifty-one of 58 complete responses were ongoing in the combination group compared with six of 10 in the sunitinib group.
The ORR was numerically, but not significantly, higher in the favorable-risk subgroup for sunitinib vs. the combination (50% vs. 39%). However, the complete response rate (8% vs. 4%) and proportion of ongoing complete responses (n = 9 of 10 vs. n = 2 of 5) were higher in the combination group.
Grade 3 or grade 4 treatment-related adverse events occurred among 47% of patients assigned the combination vs. 64% of patients treated with sunitinib.
“Tracking high-grade treatment-related adverse events over time, we see a difference in early vs. chronic toxicity burden between the two arms, with sunitinib toxicity continuing despite dose adjustments,” Tannir said.
Overall, regardless of risk category, nivolumab-ipilimumab conferred “impressive” response rates, and these responses were “deeper and more durable” than with sunitinib, Tannir said. – by Alexandra Todak
Tannir NM, et al. Abstract 547. Presented at: Genitourinary Cancers Symposium; Feb. 14-16, 2019; San Francisco.
Disclosures: Tannir reports honoraria or research from, consultant/advisory board roles with, or travel expenses from Bristol-Myers Squibb, Calithera Biosciences, Eisai Medical Research, Epizyme, Exelixis, Mirati Therapeutics, Nektar, Novartis, Oncorena, Ono Pharmaceutical and Pfizer. Please see the abstract for all other authors’ relevant financial disclosures.