Regimen improves outcomes in advanced renal cell carcinoma regardless of prior nephrectomy
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Nivolumab plus cabozantinib improved outcomes compared with sunitinib regardless of prior nephrectomy among patients with advanced renal cell carcinoma, according to study results presented at International Kidney Cancer Symposium.
However, the magnitude of benefit in terms of PFS and objective response rate appeared greater among patients who had undergone prior nephrectomy than those who had not.
“These data, together with ongoing prospective studies exploring the role and sequence of nephrectomy [for] patients with advanced renal cell carcinoma who receive systemic therapy, will continue to inform optimal ... treatment strategies,” Camillo Porta, MD, professor at University of Pavia in Italy, and colleagues wrote. “Overall, these results continue to support nivolumab plus cabozantinib as a first-line treatment option for patients with advanced renal cell carcinoma.”
Nivolumab (Opdivo, Bristol Myers Squibb) is an anti-PD-1 antibody. Cabozantinib (Cabometyx, Exelixis) is a multitargeted tyrosine kinase inhibitor.
In the randomized phase 3 CheckMate -9ER trial, researchers assigned 651 patients with previously untreated advanced or metastatic renal cell carcinoma with a clear cell component to nivolumab and cabozantinib (n = 323) or standard-of-care sunitinib (Sutent, Pfizer; n = 328).
Researchers administered IV nivolumab at a flat dose of 240 mg every 2 weeks and cabozantinib orally at a dose of 40 mg once daily. Sunitinib was administered orally at a dose of 50 mg daily in a 4-weeks-on, 2-weeks-off cycles. Treatment continued until disease progression or unacceptable toxicity.
The FDA approved nivolumab-cabozantinib for first-line treatment of advanced renal cell carcinoma based on previously reported results from the intention-to-treat population. Those results, based on median follow-up of 23.5 months (range, 16-36), showed improvement in median PFS (17 months vs. 8.3 months; HR = 0.52; 95% CI, 0.43-0.64), median OS (not reached vs. 29.5 months; HR = 0.66; 95% CI, 0.5-0.87) and ORR (54.8% vs. 28.4%; OR = 3.2; 95% CI, 2.3-4.4).
Patients with advanced renal cell carcinoma who do not undergo upfront nephrectomy typically have a poor prognosis, so Porta and colleagues conducted an exploratory post hoc analysis to assess efficacy outcomes among subgroups defined by baseline nephrectomy status.
Of the 651 patients in the trial, 455 underwent prior nephrectomy (nivolumab-cabozantinib, n = 222; sunitinib, n = 233) and 196 had not (nivolumab-cabozantinib, n = 101; sunitinib, n = 95).
A higher percentage of patients who underwent prior nephrectomy had International Metastatic Renal Cell Carcinoma Database favorable-risk disease. Other baseline characteristics appeared similar between groups.
Results showed improved PFS with nivolumab-cabozantinib among patients who underwent prior nephrectomy (19.4 months vs. 8.9 months; HR = 0.5; 95% CI, 0.39-0.64) and those who had not (11.3 months vs. 7 months; HR = 0.62; 95% CI, 0.43-0.89).
Researchers reported longer median OS with the combination in the nephrectomy group (not reached in either group; HR = 0.54; 95% CI, 0.37-0.78) but not in the no-nephrectomy group (23.8 months vs. 29.5 months; HR = 0.87; 95% CI, 0.57-1.35).
“OS probabilities at 12 and 18 months were higher with nivolumab plus cabozantinib vs. sunitinib among patients without prior nephrectomy, yet no notable overall difference between arms was observed,” Porta and colleagues wrote. “Longer follow-up may be needed to determine survival benefits with either treatment in this subgroup.”
Results showed longer median duration of response for patients assigned nivolumab-cabozantinib in the nephrectomy group (22 months vs. 13.8 months) and no-nephrectomy group (17.2 months vs. 9.9 months).
Assessment by blinded independent central review showed a higher ORR among patients assigned nivolumab-cabozantinib in the nephrectomy group (60.8% vs. 30.5%) and the no-nephrectomy group (41.6% vs. 23.2%).
Among patients who underwent nephrectomy within 3 months of trial enrollment, the nivolumab-cabozantinib appeared superior with regard to median PFS (9.5 months vs. 6.8 months; HR = 0.44; 95% CI, 0.28-0.7), median OS (not reached vs. 26.8 months; 95% CI, 0.51-0.28-0.94) and ORR (50% vs. 22.2%).
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Porta C, et al. Abstract E40. Presented at: International Kidney Cancer Symposium; Nov. 5-6, 2021; Austin, Texas.
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