(UroToday.com) The 2026 ASCO annual meeting featured a kidney cancer session and a presentation by Dr. Amishi Shah discussing a subgroup analysis of the phase 3 CheckMate-9ER trial assessing cabozantinib + nivolumab versus sunitinib in patients with advanced RCC and liver metastasis. Liver metastases occur in ~18-20% of patients with advanced RCC and are associated with poor survival outcomes. In the phase 3 CheckMate 9ER trial, cabozantinib + nivolumab treatment significantly improved progression free survival, overall survival, and objective response rate versus sunitinib in patients with first line advanced RCC,1 including those with baseline liver metastasis.2 At the ASCO 2026 annual meeting, Dr. Shah and colleagues presented results of an exploratory analyses of outcomes in additional subgroups including patients with no liver metastasis and those with liver metastasis plus other metastatic sites.
Overall, 651 patients with clear cell advanced RCC were randomized 1:1 to cabozantinib (40 mg daily) + nivolumab (240 mg every 2 weeks) or sunitinib (50 mg daily for 4 weeks of 6-week cycles). Progression free survival (primary endpoint) and objective response rate were per RECIST v1.1 by blinded independent central review. The median follow-up was 67.6 months. Patient subgroups analyzed included those with liver metastasis or no liver metastasis at baseline and those with bone, lung, lymph node, or adrenal gland metastasis in addition to liver metastasis.
There were 129 patients who had liver metastasis at baseline (cabozantinib + nivolumab, n = 73; sunitinib, n = 56). Baseline characteristics were generally consistent between treatment arms among patients with liver metastasis and no liver metastasis:
Objective response rate was higher, and progression free survival, overall survival, and duration of response were prolonged with cabozantinib + nivolumab versus sunitinib regardless of the presence or absence of liver metastases:
As expected, progression free survival and overall survival outcomes were less favorable in patients with liver metastases versus without, and worst among those with concomitant liver and bone metastases at baseline; however, the relative benefit of cabozantinib + nivolumab versus sunitinib was consistent across all metastatic site subgroups examined:
Among patients with liver metastases, the benefit of cabozantinib + nivolumab was observed across subgroups according to age, prior nephrectomy, IMDC prognostic risk score, and additional sites of metastases. The following Forest plot is for progression free survival:
And the following Forest plot highlights overall survival:
Rates of subsequent systemic anticancer therapy in the cabozantinib + nivolumab arm versus the sunitinib arm, respectively, were 33% versus 45% in patients with liver metastases and 42% versus 53% in patients without liver metastases. Clinical outcomes were also improved with cabozantinib + nivolumab versus sunitinib in patients with concomitant liver plus bone metastases and liver plus lung metastases:
The presence of liver metastases did not negatively impact cabozantinib dose exposure or the rate of treatment emergent adverse events leading to dose reduction of cabozantinib:
Rates of any grade and grade 3-4 treatment related adverse events with cabozantinib + nivolumab versus sunitinib were similar in patients with and without liver metastases:
Irrespective of the presence or absence of liver metastases, the most common any grade treatment related adverse event among patients treated with cabozantinib + nivolumab were diarrhea, hypothyroidism, hypertension, and palmar-plantar erythrodysesthesia syndrome:
Liver function test results were similar for patients treated with cabozantinib + nivolumab, regardless of the presence of liver metastases:
Dr. Shah concluded this presentation discussing a subgroup analysis of the phase 3 CheckMate-9ER trial assessing cabozantinib + nivolumab versus sunitinib in patients with advanced RCC and liver metastasis with the following take home points:
- First line treatment with cabozantinib + nivolumab improved efficacy outcomes versus sunitinib in patients with or without liver metastases from advanced RCC at baseline
- Among patients with liver metastases, a subgroup with a poor prognosis, the benefit with cabozantinib plus nivolumab versus sunitinib was consistent, regardless of concomitant metastases in the bone or lung
- The safety profile of cabozantinib + nivolumab was similar among patients with and without liver metastases, with no increase in hepatotoxicity, suggesting the combination has a manageable safety profile in patients with advanced RCC and liver metastases
- The similar hepatic safety and comparable cabozantinib exposure in patients with and without liver metastases indicate that patients were able to remain on and benefit from treatment regardless of liver metastasis status
Presented by: Amishi Shah, MD, The University of Texas, MD Anderson Cancer Center, Houston, TX
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the American Society of Clinical Oncology Genitourinary (ASCO) Annual Meeting held in Chicago, IL between May 29th and June 1st, 2026
References:
- Choueiri TK, Powles T, Burotto M, et al. Nivolumab plus cabozantinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2021 Mar 4;384(9):829-841.
- Motzer RJ, Escudier B, Burotto M, et al. Final analysis of nivolumab plus cabozantinib for advanced renal cell carcinoma from the randomized phase III CheckMate 9ER trial. Ann Oncol. 2026 Jan;37(1):33-43.