Gabriele Calvanese

Background: Immune checkpoint inhibitor–tyrosine kinase inhibitor combinations represent a standard first-line option for metastatic renal cell carcinoma (mRCC). However, patients enrolled in pivotal trials often differ from those treated in routine practice. We report real-world outcomes of pembrolizumab plus axitinib within the Campania Oncology Network. Methods: We conducted a multicenter retrospective study including consecutive treatment-naïve mRCC patients who received first-line pembrolizumab plus axitinib between January 2021 and November 2023 across eight regional centers. The primary endpoints were progression-free survival (PFS) and overall survival (OS); secondary endpoints included objective response rate (ORR) and safety. Results: A total of 117 patients were included. IMDC risk was favorable in 19.6%, intermediate/poor in 65%, and unknown in 15.4%. Median age was 59 years, and 53.8% had ECOG performance status ≥ 1. Clear-cell histology accounted for 87.2% of cases; brain metastases were present in 36%. After a median follow-up of 12.8 months, median PFS was 15.1 months (95% CI 9.6–NR), and median OS was not reached. ORR was 27.3%, with a disease control rate of 79.5%; patients with non-clear-cell histology showed an ORR of 41.7%. Disease progression was the main cause of treatment discontinuation (49%), while adverse events (AEs) led to discontinuation in 6% of cases. Grade ≥3 AEs occurred in 14% of patients. Most toxicities were grade 1–2, including diarrhea (23.9%), asthenia (18%), hypothyroidism (12.8%), and hypertension (9.4%). Grade 1–2 AEs were significantly more frequent in females compared with males (57.6% vs. 35.7%, p = 0.05). Conclusions: In this consecutive regional cohort, pembrolizumab plus axitinib showed clinically relevant disease control, although ORR was lower than in pivotal trials. Performance status emerged as a key prognostic factor. Real-world data from oncology networks may support personalized first-line treatment decisions in mRCC.