Nivolumab plus cabozantinib was safe and active for the real-world frontline treatment of patients with advanced RCC.
Nivolumab (Opdivo) in combination with cabozantinib (Cabometyx) was effective for the real-world frontline treatment of patients with advanced renal cell carcinoma (RCC), including those with poor prognostic features, according to data from the phase 4 CaboCombo trial (NCT05361434) presented during the 2026 International Kidney Cancer Symposium (IKCS): Europe.1
In the efficacy population (n = 308), the 18-month real-world overall survival (rwOS) rate was 74% (95% CI, 69%-79%). The median real-world progression-free survival (rwPFS) was 14.0 months (95% CI, 12.2-16.0). No new safety signals were reported with the regimen.
“The prospective CaboCombo study final analysis demonstrates that [first-line] cabozantinib plus nivolumab delivers durable effectiveness and manageable tolerability with [at least] 18 months’ follow-up in the real‑world treatment of patients with advanced RCC,” Philippe Barthélémy, PhD, of the Medical Oncology Department at Hôpitaux Universitaires de Strasbourg in France, and his coauthors wrote in a poster presentation of the data.
CaboCombo was a prospective, international, observational study that enrolled adult patients with clear cell advanced RCC who received frontline cabozantinib plus nivolumab in the real-world setting.1 The study included patients who were 18 years or older with previously untreated advanced RCC with a clear cell component who were treated between September 22, 2022, and April 24, 2024.
Patients received the agents according to approved local labels until disease progression, unacceptable toxicity, or withdrawal of consent. The decision to prescribe cabozantinib plus nivolumab was made independently by the treating physician prior to enrollment in CaboCombo.
CaboCombo aimed to assess the real-world effectiveness and tolerability of frontline cabozantinib plus nivolumab in patients with advanced RCC. The primary end point was the 18-month rwOS rate. Secondary end points included rwPFS, best real-world overall response, real-world overall response rate (rwORR), real-world disease control rate (rwDCR), real-world time to response (rwTTR), real-world duration of response (rwDOR), patterns of use, and safety.
At baseline, the median age in the overall population was 67.0 years (IQR, 59.0-74.0). Most patients had intermediate-risk disease per International Metastatic RCC Database Consortium Risk Score (54.4%), clear cell histology (98.1%), metastatic disease (93.5%), 1 metastatic site at treatment initiation (51.7%), and lung metastases (56.6%), and had undergone prior nephrectomy (57.2%).
Additional findings from CaboCombo showed that among evaluable patients (n = 280), the rwORR was 62.1% (95% CI, 56.2%-67.8%); the complete response rate was 8.2% (95% CI, 5.3%-12.1%). The rwDCR was 91.8% (95% CI, 87.9%-94.7%). The median rwTTR was 3.1 months (IQR, 2.6-4.0) and the median rwDOR was 17.2 months (95% CI, 13.8-21.2).
In the safety population (n = 311), any-grade treatment-emergent adverse effects (TEAEs) occurred in 96.5% of patients; serious TEAEs leading to death occurred in 7.4% of patients. Grade 3 (58.8%), grade 4 (9.3%), serious (44.4%), cabozantinib-related (89.1%), nivolumab-related (67.5%), and cabozantinib- or nivolumab-related (90.7%) TEAEs were also reported. TEAEs leading to discontinuation of cabozantinib, nivolumab, and cabozantinib or nivolumab occurred at rates of 32.8%, 22.5%, and 42.1%, respectively. The most common any-grade TEAEs related to the combination included diarrhea (44.1%), asthenia (34.4%), palmar-plantar erythrodysaesthesia syndrome (28.3%), decreased appetite (16.7%), mucosal inflammation (16.4%), and hypothyroidism (15.4%).
“CaboCombo results were consistent with those from the CheckMate 9ER trial, for a more frail and elderly population,” Barthélémy and his coauthors wrote in their conclusion.
