Among patients with previously untreated, advanced renal cell carcinoma (RCC), treatment with Opdivo (nivolumab) plus Cabometyx (cabozantinib) resulted in long-term efficacy and manageable safety versus treatment with the standard of care, Sutent (sunitinib), study results have shown.
Final follow-up results from the phase 3 CheckMate 9ER trial were presented at the 2025 ASCO Genitourinary Cancer Symposium.
At the median follow up of 67.6 months for the intention to treat population, the median progression-free survival (PFS) was 16.4 months for patients who received Opdivo/CabometyxCabometyx and 8.3 months for those who received Sutent; median overall survival (OS) was 46.5 months versus 35.5 months, respectively, and median duration of response (DOR) was 22 months versus 15.2 months.
The overall response rate (ORR) was 55.7% versus 27.4% for patients in the Opdivo versus Sutent arms, respectively. Of patients who received Opdivo/Cabometyx, 20.1% experienced a partial response (PR) with 60% or more tumor reduction, and 21.7% received a PR with less than 60% tumor reduction. In the Opdivo/Cabometyx arm versus the Sutent arm, complete responses were observed in 45 and 15 patients, PRs in 135 and 75, stable disease in 104 and 136, progressive disease in 21 and 47 and unknown in 18 and 55.
“Long term efficacy benefit was observed with [Opdivo plus Cabometyx] over [Sutent] in these final results from the CheckMate 9ER trial, with a median of 67.6 months follow-up,” presenting author Dr. Robert J. Motzer, section head of Kidney Cancer in Genitourinary Oncology Service and Jack and Dorothy Byrne Chair in Clinical Oncology at Memorial Sloan Kettering Cancer Center, and coauthors, wrote in the presentation. “The results continue to support [Opdivo plus Cabometyx] as a standard of care for previously untreated advanced RCC.”
A total of 651 patients were enrolled in the trial and randomly assigned to receive 240 mg of intravenous Opdivo every two weeks plus 40 mg of oral Cabometyx daily (323 patients) or 50 mg of oral Sutent daily on four weeks on, two weeks off schedule (328 patients). Eligible patients had previously untreated advanced or metastatic RCC with a clear cell component who were in any International Metastatic RCC Database Consortium (IMDC) risk group.
Of patients in the IMDC favorable risk group, the median PFS in the Opdivo/Cabometyx group (74 patients) was 21.4 months versus 12.8 months in the Sutent group (72 patients); median OS was 53.7 months versus 58.9 months, respectively, and ORR was 66.2% versus 43.1%.
In the IMDC intermediate or poor risk group, the median PFS in the Opdivo/Cabometyx group (249 patients) was 15.4 months versus 7.1 months in the Sutent group (256 patients); median OS was 43.9 months versus 29.2 months, respectively, and ORR was 52.6% versus 23%.
Patients with liver metastases had a median PFS was 10.9 months in the Opdivo/Cabometyx group (73 patients) and 6.2 months in the Sutent group (56 patients); median OS was 37.6 months and 22.1 months, respectively; ORR was 52.1% and 21.4%.
Of patients with bone metastases, the median PFS was 13.8 months in the Opdivo/Cabometyx group (79 patients) and 5.3 months in the Sutent group (75 patients); median OS was 34.8 months and 20.7 months, respectively; ORR was 49.4% and 9.3%.
Those with lung metastases demonstrated a median PFS was 16.4 months in the Opdivo/Cabometyx group (241 patients) and 8.3 months in the Sutent group (251 patients); median OS was 47.5 months and 32.4 months, respectively; ORR was 57.3% and 27.9%.
Additionally, 93% of patients in the Opdivo/Cabometyx group and 95% in the Sutent group discontinued treatment; 43% and 55%, respectively, received subsequent systemic therapies; 26% and 31% received two or more subsequent systemic therapies; and the most common was any VEGFR inhibitor (79%) in the Opdivo/Cabometyx group and any PD-L1 inhibitor (81%) in the Sutent group.
The median duration of therapy was 21.8 months in the Opdivo/Cabometyx group and 8.9 months in the Sutent group; 62% and 55% of patients had at least one dose reduction; and the median time to first dose reduction was 4.1 months and two months.
Regarding safety, common treatment-related side effects of any grade occurred in 98% of patients in the Opdivo/Cabometyx group and 93% of the Sutent group, and grade 3 (severe)/4 (life-threatening) treatment-related side effects occurred in 68% and 55%, respectively. The most common treatment-related side effects of any grade were diarrhea (60% and 46%, respectively), palmar-plantar erythrodysesthesia (39% and 42%), hypertension (34% and 35%) and hypothyroidism (37% and 31%). Also, 22% of patients to receive Opdivo/Cabometyx were administered corticosteroids to manage immune-mediated side effects of any grade. Any grade treatment-related side effects led to discontinuation in 28% and 11%, respectively.
Reference
“Nivolumab plus cabozantinib (N+C) vs sunitinib (S) for previously untreated advanced renal cell carcinoma (aRCC): Final follow-up results from the CheckMate 9ER trial.” By Dr. Robert J. Motzer et al., Journal of Clinical Oncology.
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