Application of extended immunotherapy in advanced clear cell renal cell carcinoma treated with first-line combination of immune-checkpoint inhibitor and tyrosine kinase inhibitor.

Purpose: To evaluate the efficacy and safety of extended immunotherapy in first-line immune checkpoint inhibitors (ICIs)-tyrosine kinase inhibitors (TKIs) combination treatment for advanced renal cell carcinoma (RCC).

Patients and methods: We retrospectively analyzed data from patients with advanced RCC who received first-line ICIs-TKIs combination treatment at West China Hospital of Sichuan University between October 2018 and July 2024. Patients who are assessed as having a disease control status after 2 years of continuous treatment will continue to receive immune checkpoint inhibitors until the inhibitors are discontinued due to disease progression or death.

Result: A total of 86 patients were screened and 14 patients diagnosed with clear cell RCC (ccRCC) were enrolled. After 65 months of follow-up, three-year progression-free survival (PFS) rate was 71.4% and 4 year PFS rate was 59.5%. The 5 year overall survival (OS) rate was 58.3%. During extended treatment, one patient (7.1%) experienced a transition from stable disease (SD) to partial response (PR) and two patients (14.3%) experienced a transition from PR to complete response (CR). The best tumor shrinkage rates presenting after 24 months had longer PFS and OS compared to those presenting within 24 months (median PFS: not reached vs. 36 months; Hazard Ratio (HR) = 0.10, 95% CI 0.01-0.80, P = 0.03). For safety, extended immunotherapy did not increase treatment-related toxicities compared to safety profile before 24 months.

Conclusion: Our analysis of real-world data indicates that patients with extended immunotherapy after 24 months had potential survival benefits and manageable toxicity. Large-scale, prospective studies are still needed to further verify the conclusion.