Cabozantinib Plus Durvalumab in Patients With Advanced Urothelial Carcinoma After Platinum Chemotherapy: Safety and Preliminary Activity of the Open-Label, Single-Arm, Phase 2 ARCADIA Trial.
Angiogenesis
Salvage therapy
advanced urothelial carcinoma
cabozantinib
durvalumab
Journal
Clinical genitourinary cancer
ISSN: 1938-0682
Titre abrégé: Clin Genitourin Cancer
Pays: United States
ID NLM: 101260955
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
received:
01
02
2021
revised:
27
03
2021
accepted:
05
04
2021
pubmed:
20
5
2021
medline:
25
2
2023
entrez:
19
5
2021
Statut:
ppublish
Résumé
Durvalumab and cabozantinib have shown single-agent activity in patients with metastatic urothelial carcinoma (UC). ARCADIA is a phase 2 study evaluating their combination in patients with platinum-treated, advanced UC (NCT03824691). Herein, we report the results of the planned interim safety analysis and the preliminary activity. Patients with Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1, UC and non-UC histology, and failure of a maximum of two regimens received cabozantinib 40 mg daily, orally, in combination with durvalumab 1500 mg, intravenously, every 28 days. Response was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 every two cycles and by fluorodeoxyglucose positron emission tomography (FDG-PET) scans. As of August 20, 2020, 16 patients were enrolled with a median follow-up of 6.7 months (range, 2-11). Four patients (25%) had ECOG PS 1 and had received two prior regimens. No grades 3 or 4 treatment-related adverse events (TRAEs) occurred within the first two cycles. The most common grades 1 and 2 TRAEs were fatigue (7, 43.8%), diarrhea (5, 31.3%), and dysphonia (5, 31.3%). Objective responses were seen in six patients (37.5%; 95% confidence interval, 15.2-64.6), including two complete responses (12.5%). One additional patient with bone-only disease obtained a decrease in FDG uptake and in circulating tumor DNA consistent with response. Angiogenesis-related gene alterations were found in 57% responders versus 0% nonresponders. The durvalumab and cabozantinib combination was safe and endowed with preliminary clinical activity in patients with advanced UC. Mature results will clarify the role of cabozantinib and that of tumor biomarkers in this tumor type.
Sections du résumé
BACKGROUND
Durvalumab and cabozantinib have shown single-agent activity in patients with metastatic urothelial carcinoma (UC). ARCADIA is a phase 2 study evaluating their combination in patients with platinum-treated, advanced UC (NCT03824691). Herein, we report the results of the planned interim safety analysis and the preliminary activity.
PATIENTS AND METHODS
Patients with Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1, UC and non-UC histology, and failure of a maximum of two regimens received cabozantinib 40 mg daily, orally, in combination with durvalumab 1500 mg, intravenously, every 28 days. Response was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 every two cycles and by fluorodeoxyglucose positron emission tomography (FDG-PET) scans.
RESULTS
As of August 20, 2020, 16 patients were enrolled with a median follow-up of 6.7 months (range, 2-11). Four patients (25%) had ECOG PS 1 and had received two prior regimens. No grades 3 or 4 treatment-related adverse events (TRAEs) occurred within the first two cycles. The most common grades 1 and 2 TRAEs were fatigue (7, 43.8%), diarrhea (5, 31.3%), and dysphonia (5, 31.3%). Objective responses were seen in six patients (37.5%; 95% confidence interval, 15.2-64.6), including two complete responses (12.5%). One additional patient with bone-only disease obtained a decrease in FDG uptake and in circulating tumor DNA consistent with response. Angiogenesis-related gene alterations were found in 57% responders versus 0% nonresponders.
CONCLUSION
The durvalumab and cabozantinib combination was safe and endowed with preliminary clinical activity in patients with advanced UC. Mature results will clarify the role of cabozantinib and that of tumor biomarkers in this tumor type.
Identifiants
pubmed: 34006499
pii: S1558-7673(21)00086-0
doi: 10.1016/j.clgc.2021.04.001
pii:
doi:
Substances chimiques
Anilides
0
Antibodies, Monoclonal
0
Pyridines
0
cabozantinib
1C39JW444G
durvalumab
28X28X9OKV
Platinum
49DFR088MY
Banques de données
ClinicalTrials.gov
['NCT03824691']
Types de publication
Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
457-465Informations de copyright
Copyright © 2021. Published by Elsevier Inc.