Bone targeting agents, but not radiation therapy, improves survival in patients with bone metastases from advanced urothelial carcinoma receiving pembrolizumab: results from the ARON-2 study

• DOI: 10.1007/s10238-023-01235-6
• Publication Date: 2023-11-02T11:03:01Z
• Authors: Matteo Santoni; Francesco Massari; Hideki Takeshita; Jose Carlos Tapia; Michele Dionese; Renate Pichler; Mimma Rizzo; Elaine T. Lam; Enrique Grande; Robert Kemp; Javier Molina-Cer...; Fabio Calabrò; Deniz Tural; Zsófia Küronya; Jakub Kucharz; Ondrej Fiala; Emmanuel Seront; Ray Manneh Kopp; Halima Abahssain; Jindrich Kopecky; Angelo Martignetti; Ravindran Kanesvaran; Roubini Zakopoulou; Jawaher Ansari; Johannes Landmesser; Veronica Mollica; Camillo Porta; Joaquim Bellmunt; Samer Salah; Daniele Santini
• Keywords: Bone metastase; ARON-2 study; Survival; 616; NCT05290038; Urothelial cancer; 610; Immunotherapy; Tumor response; Pembrolizumab; Real-world data; 3. Good health; ARON-2 study; Bone metastases; Immunotherapy; NCT05290038; Pembrolizumab; Real-world data; Survival; Tumor response; Urothelial cancer

The ARON-2 study (NCT05290038) aimed to assess the real-world efficacy of pembrolizumab in patients recurred or progressed after platinum-based chemotherapy. This retrospective analysis reports the outcomes of urothelial carcinoma (UC) patients with bone metastases (BM). Medical records of patients with documented metastatic UC treated by pembrolizumab as second-line therapy were reviewed from60 institutions in 20 countries. Patients were assessed for Overall Response Rate (ORR), Progression-Free Survival (PFS), and Overall Survival (OS). Univariate and multivariate analyses were used to explore the association of variables of interest with OS and PFS. 881 patients were included; of them, 263 (30%) presented BM. Median follow-up time was 22.7 months. Patients with BM showed both shorter median OS (5.9 months vs 13.1 months, p < 0.001) and PFS (3.5 months, vs 7.3 months, p < 0.001) compared to patients without BM. Patients who received bone targeted agents (BTAs) showed a significantly longer median OS (8.5 months vs 4.6 months, p = 0.003) and PFS (6.1 months vs 3.2 months, p = 0.003), while no survival benefits were observed among patients who received radiation therapy for BM during pembrolizumab treatment compared to those who did not. In multivariate analysis, performance status, concomitant liver metastases, and the lack of use of BTAs were significantly associated with worse OS and PFS. Bone involvement in UC patients treated with pembrolizumab predicts inferior survival. Poor performance status and liver metastases may further worsen outcomes, while the use of BTAs is associated with improved outcomes.