CheckMate 9ER Regimen Shows Efficacy Regardless of Prior Nephrectomy in RCC

An exploratory subgroup analysis of the CheckMate 9ER trial (NCT03141177) demonstrated significant benefits to progression-free survival (PFS) and objective response rate (ORR) for patients with renal cell carcinoma (RCC) receiving nivolumab (Opdivo) and cabozantinib (Cabometyx) regardless of whether they had a prior nephrectomy, according to data from the 2021 European Society for Medical Oncology Congress.1

“Overall survival [OS] benefits with nivolumab plus cabozantinib versus sunitinib [Sutent] were observed in patients with prior nephrectomy and OS probabilities were higher with nivolumab plus cabozantinib in the subgroup without prior nephrectomy,” Camillo Guglielmo Porta, MD, said in his presentation.

In this first-line phase 3 study, patients with advanced RCC in the intent-to-treat (ITT) achieved superior OS, PFS, and ORR with nivolumab plus cabozantinib compared with sunitinib after a minimum follow-up of 10.6 months, this efficacy was also maintained after 16.0 months of minimum follow-up. Patients on the trial were randomized 1:1 to nivolumab at 240 mg every 2 weeks and cabozantinib at 40 mg once daily versus sunitinib at 50 mg once daily 4 weeks in a 6-week cycle.

Patients with advanced RCC who do not receive nephrectomy up front usually have a poor prognosis and these patients have limited data with targeted therapies and immunotherapy combinations. The CheckMate 9ER exploratory post hoc analysis assessed efficacy outcomes with nivolumab/cabozantinib versus sunitinib in patients with baseline nephrectomy status after a minimum of 16-months follow-up.

Out of 651 patients in the ITT population, 455 had prior nephrectomy—222 in the nivolumab/cabozantinib arm and 233 in the sunitinib arm—and 196 did not have prior nephrectomy—101 receiving nivolumab/cabozantinib and 95 receiving sunitinib. The baseline characteristics of these 2 groups were similar, but more patients had International Metastatic RCC Database Consortium favorable-risk disease in those with prior nephrectomy in both treatment arms.

The hazard ratio for progression favored nivolumab/cabozantinib over sunitinib regardless of nephrectomy status, with a longer median PFS of 19.4 months versus 8.9 months, respectively, with prior nephrectomy (HR, 0.50; 95% CI, 0.39-0.64) and 11.3 months compared with 7.0 months without prior nephrectomy (HR, 0.62; 95% CI, 0.43-0.89).

Additionally, the PFS probabilities were higher with nivolumab/cabozantinib at 62% versus 37% at 12 months and 54% versus 27% at 19 months, respectively, with prior nephrectomy. Without prior nephrectomy, the PFS probabilities were 47% versus 35% and 33% versus 18% at 12 and 18 months, respectively.

In the nivolumab/cabozantinib group, OS probabilities were also consistently higher. Patients with prior nephrectomy had higher 12- and 18-month OS probabilities with nivolumab/cabozantinib. However, the OS probabilities at 12 and 18 months did not show a notable difference between arms were observed.

The median OS was not reached (NR) with nivolumab/cabozantinib and sunitinib in the subgroup with prior nephrectomy (HR, 0.54; 95% CI, 0.37-0.78). Patients without prior nephrectomy had a median OS of 23.8 months (95% CI, 21.4-NR) with nivolumab/cabozantinib and 29.5 months (95% CI, 19.4-29.5) with sunitinib (HR, 0.87; 95% CI, 0.57-1.35).

With nivolumab/cabozantinib, the ORR was higher in both subgroups. With prior nephrectomy, the ORR was 60.8% compared to 30.5% with nivolumab/cabozantinib and sunitinib, respectively. The ORR was 41.6% versus 23.2% without prior nephrectomy. The median time to response was shorter and there was a notably higher with nivolumab/cabozantinib in both subgroups.

“Notable efficacy benefits were also observed with nivolumab plus cabozantinib versus sunitinib in patients when there was prior nephrectomy within 3 months of trial enrollment,” Porta, an adjunct professor at the University of Pavia in Italy, said.

There were 54 out of the 222 patients (24.3%) who underwent nephrectomy within 3 months of enrollment in the nivolumab/cabozantinib group, and 72 of the 233 (30.9%) patients in the sunitinib group also underwent nephrectomy. The ORR was higher with nivolumab/cabozantinib at 50.0%, with 5.6% of patients achieving complete response and 44.4% achieving partial response, in this subgroup. The sunitinib arm had an ORR of 22.2% in this subgroup, with a 2.8% complete response rate and 19.4% partial response rate.

In patients without prior nephrectomy, 61.4% given nivolumab/cabozantinib and 66.3% given sunitinib had target kidney lesions. The ORR was higher nivolumab/cabozantinib than sunitinib at 35.5% and 20.6%, respectively. No patients achieved complete response in this subgroup. A 30% or more reduction in target kidney lesions was achieved in 50.9% of patients in the nivolumab/cabozantinib arm and 29.4% in the sunitinib arm. The median reduction was 30% versus 16%, respectively.

“As a whole, these data together with other ongoing studies exploring the role in sequencing nephrectomy will continue to inform us about optimal metastatic kidney cancer treatment strategies. Overall, however, these results continue to support nivolumab plus cabozantinib as a first-line treatment option for patients with advanced RCC,” Porta concluded.

_Reference:

_{Porta C, Burotto M, Suarez C, et al. First-line nivolumab + cabozantinib vs sunitinib in patients (pts) with advanced renal cell carcinoma (aRCC) in subgroups based on prior nephrectomy in the CheckMate 9ER trial. Presented at: 2021 European Society for Medical Oncology Congress; September 16-21, 2021; virtual. Abstract 663P.}