Abstract
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.
Keywords
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Article Info
Publication History
Published online: April 20, 2021
Accepted:
April 5,
2021
Received in revised form:
March 27,
2021
Received:
February 1,
2021
Identification
Copyright
© 2021 Elsevier Inc. All rights reserved.
