Aims: First-line management of metastatic renal cell carcinoma (RCC) has evolved from tyrosine kinase inhibitor (TKI) monotherapy to immune checkpoint inhibitor (ICI)-based combinations. Australian patients have had Pharmaceutical Benefits Scheme-funded access to ipilimumab-nivolumab since 2019 and pembrolizumab-lenvatinib since 2023. Without head-to-head trials, treatment selection relies on cross-trial interpretation and clinician judgement, with limited Australian real-world evidence.
Methods: We retrospectively analysed adults with metastatic RCC commencing first-line management from March 2019 to January 2026 across four Northern Sydney cancer centres. Primary endpoint was overall survival (OS); secondary endpoints were progression-free survival (PFS), objective response rate (ORR), duration of response, subsequent therapy and safety. Survival was estimated using Kaplan-Meier methods.
Results: Among 75 patients, median follow-up was 43.6 months (0.03-83.0) and median age 66 years (27-87); 55/75 (73.3%) were male, with clear cell histology (81.3%), intermediate/poor IMDC risk (82.7%) and ≥5 metastatic sites (68.0%). First-line management comprised ipilimumab-nivolumab (50/75, 66.7%), pembrolizumab-lenvatinib (3/75, 4.0%), TKI monotherapy (10/75, 13.3%), active surveillance (8/75, 10.7%), nivolumab (2/75, 2.7%) and clinical trial participation (2/75, 2.7%).
Among ipilimumab-nivolumab-treated patients, median OS was 40.4 months (2.0-83.0), median PFS 13.3 months (0.07-77.8), ORR 49.0% (23/47 evaluable) and median response duration 14.0 months (1.9-81.1), with 4 responses ongoing beyond five years. Grade 3-4 adverse events occurred in 18/50 (36.0%) and toxicity-related discontinuation in 12/50 (24.0%). All 3 pembrolizumab-lenvatinib patients remained progression-free (12.2-24.9 months). TKI monotherapy yielded median OS 42.8 months (5.7-81.7), median PFS 9.6 months (2.1-79.0) and ORR 70.0% (7/10). 37/75 (49.3%) received subsequent therapy, most commonly cabozantinib (14/37, 37.8%), with median time to next treatment 9.2 months (2.0-71.5).
Conclusion: First-line ipilimumab-nivolumab achieved outcomes consistent with international real-world benchmarks in an older, less selected, high-burden Australian cohort. Retrospective design, small subgroups and non-randomised allocation limit interpretation. This supports prospective multicentre Australian collaboration integrating biomarkers to refine treatment selection and improve outcomes.