Durable Progression-Free and Treatment-Free Survival After Nivolumab Plus Ipilimumab Therapy in Metastatic Renal Cell Carcinoma: A Real-World Study with a 5-Year Minimum Follow-Up

BACKGROUND/OBJECTIVES: Nivolumab plus ipilimumab (IO-IO) provides durable clinical benefit in metastatic renal cell carcinoma (mRCC), yet long-term real-world data focusing on progression-free and treatment-free (PF-TF) survival remain limited. This study aimed to evaluate the long-term outcomes of IO-IO with a particular focus on the frequency and clinical characteristics of PF-TF. METHODS: We retrospectively analyzed 63 patients with mRCC treated with first-line IO-IO across eight institutions with a minimum potential follow-up of five years. Progression-free survival (PFS), PFS2, and overall survival (OS) were assessed. PF-TF was defined as absence of disease progression and any cancer-directed therapy at the five-year landmark. Clinical and treatment-related factors were compared between patients with and without PF-TF. RESULTS: The median PFS, PFS2, and OS were 7.5 (95% confidence interval [CI], 5.1-13.3), 26.2 (95% CI, 13.6-46.6), and 47.4 months (95% CI, 29.3-not reached), respectively. At 5 years, 11 patients (17%) achieved PF-TF. Baseline characteristics, IMDC risk classification, and peripheral blood biomarkers were not predictive of PF-TF. PF-TF was associated with the absence of bone metastases, presence of lymph node metastases, and occurrence of immune-related adverse events (irAEs), as well as the delayed onset of irAEs. No PF-TF patients required corticosteroid pulse therapy, and durable PF-TF was observed even after early treatment discontinuation due to adverse events. CONCLUSIONS: IO-IO demonstrated sustained long-term efficacy in real-world practice, with a subset achieving durable PF-TF. These findings highlight IO-IO as a strategy capable of providing long-term disease control with reduced treatment burden in selected patients with mRCC.