Real-world effectiveness and safety of RC48-ADC combined with PD-1 inhibitors for patients with metastatic urothelial carcinoma: A retrospective multicenter study.

Abstract

e16551 Background: RC48 antibody-drug conjugate (ADC) combined with PD-1 inhibitor has significantly impacted the treatment of metastatic urothelial carcinoma (mUC). This study aimed to assess the efficacy and safety of RC48 combined with PD-1 inhibitor as a first-line treatment for patients with mUC in a real-world clinical setting. Methods: We retrospectively collected data from patients with mUC who received RC-48 in combination with PD-1 inhibitor as first-line therapy between July 2021 and February 2024 from 3 medical centers to assess real-world antitumor efficacy and safety. Results: 63 patients with mUC were collected, with a mean age of 67 years and 71.4% were male. The most common site of metastasis was lymph nodes (77.8%), followed by lung (31.7%), bone (23.8%), liver (19.0%), and so on. The response rates were as follows: complete response in 12 patients (19.0%), partial response in 33 cases (52.4%), and stable disease in 10 cases (15.9%). The objective response rate was 71.4%, and the disease control rate was 87.3%. The median progression-free survival was 10.5 (8.8-14.6) months and the median overall survival was not reached. The most reported treatment-related adverse events were fatigue (36.5%), anemia (34.9%), pruritus (33.3%), peripheral sensory neuropathy (28.6%), and nausea (28.6%), etc. Grade III TRAEs occurred in seven patients (11.1%) and no grade IV or V TRAEs occurred. Conclusions: The use of 3-weekly cycles of RC48 in combination with PD-1 inhibitor as first-line therapy is both effective and safe for real-world patients with la/ mUC, regardless of disease status or impaired renal function. Clinical trial information: 2024KY277 . Patient demographics and clinical features in metastatic urothelial carcinoma treated. Patient Characteristics Values Total number 63 Gender(%)  Male 71.4%  Female 28.6% Age, Median（years） 50-92  ≥70, No. (%) 36.5% ECOG score(%)  0 49.2%  1 39.7%  ≥2 11.1% Cr, median (umol/L) 43-296 Baseline creatinine clearance rate(%) 　  ≥ 60 ml/min 52.4%  30–60 ml/min 39.7%  < 30 ml/min 7.9% Primary lesion(%)  Bladder 54.0%  Ureter/Renal pelvis 46.0% Prior locoregional curative treatments(%) 　  Radical tumor resection 46.0%  Partial tumor resection 15.9%  Diagnostic tumor resection 30.2%  Tumor biopsy 7.9% Organizational differentiation(%)  UC without differentiation 92.0%  UC with squamous differentiation 4.8%  UC with glandular differentiation 3.2% Metastatic site(%) 　  Lymph nodes 77.8%  Lung 31.7%  Bone 23.8%  Liver 19.0%  Peripheral tissue infiltration 15.9%  Muscles 7.9%  Abdominal cavity 6.3% HER2 status(%)  IHC 0 + 15.9%  IHC 1 + 20.6%  IHC 2 + 39.7%  IHC 3 + 23.8% PD-L1 expression(%)  ≥10% 14.3%  <10% 66.7% Uncertain 19.0% Surgery(%) Radical resection 46% Partial resection 15.9% Diagnostic resection 30.2% Tumor biopsy 7.9% Treatment plan RC48 combined with Toripalimab 79.4% RC48 combined with Tislelizumab 20.6% RC48 cycles, median (IQR) 1-24