(UroToday.com) The 2023 ESMO annual meeting included a session on urothelial carcinoma, featuring a presentation by Dr. Patrizia Giannatempo discussing interim results from the phase 2 ARCADIA trial assessing activity of cabozantinib + durvalumab in patients with advanced non-urothelial-carcinoma variant histologies or urothelial carcinoma after platinum-based chemotherapy.
Combining multi-targeted receptor tyrosine kinase inhibitors with checkpoint inhibitors has shown synergistic effect in patients with urothelial carcinoma due to the immunomodulatory propriety of VEGFR inhibitors. Dr. Giannatempo and colleagues investigated if the combination of cabozantinib and durvalumab in patients with advanced urothelial carcinoma and non-urothelial carcinoma histology in a phase II study. At the 2023 ESMO annual congress, they presented preliminary results of the interim analysis.
In the ARCADIA study, patients with urothelial carcinoma or non-urothelial carcinoma histology recurred/progressed after failure of platinum-based chemotherapy were enrolled. Patients received cabozantinib 40 mg daily orally and durvalumab 1500 mg IV every 28 days, until disease progression (by RECIST 1.1) or unacceptable toxicity. The primary endpoint of the study was OS, and secondary endpoints included safety, objective response-rate (ORR), and progression-free survival (PFS).
There were 71 patients enrolled from September 2019 to February 2023, with this interim analysis being performed after obtaining at least one post-baseline tumor assessment data from 62 patients. The median follow-up was 23.5 months (IQ range: 7.7 – 27.7 months). With regards to baseline characteristics, 27.4% female, the median age was 64 years (IQ range: 42– 70 yrs), and 20 patients (34%) had a pure/predominant non-urothelial carcinoma variant histology:
- 9 (45%) squamous differentiation/sarcomatoid
- 5 (25%) adenocarcinoma
- 4 (20%) small-cell neuroendocrine
- 1 (5%) clear-cell
- 1 nested variant histology (5%)
In 58 patients, 12 (20%) had complete responses and 11 (16%) had partial responses, with the ORR being 39.7% (95% CI, 27.1 – 53.4), and the disease control rate was 69.0% (95% CI, 55.5 – 80.5). In non-urothelial carcinoma histology cohort, the ORR was 45.0% (95% CI, 23.1 – 68.5). The median PFS was 7.4 months (95% CI, 4.9 – 20.1 months) and median OS was 11.8 months (95% CI, 6.9 – 24.1). The duration of response (DOR) was 8.18 months (95% CI, 4.0 – 21.2), and 42 (67.7%) of 62 patients had all-grade treatment-related adverse events. Among these patients, 7 (16.7%) reported grade ≥ 3 treatment-related adverse events:
Dose-reductions of cabozantinib were needed in 26 patients (41.9%), and no treatment-related deaths were reported.
Dr. Giannatempo concluded her presentation discussing interim results from the phase 2 ARCADIA trial assessing activity of cabozantinib + durvalumab in patients with advanced non-urothelial-carcinoma variant histologies or urothelial carcinoma after platinum-based chemotherapy with the following concluding statements:
- Cabozantinib in combination with durvalumab showed promising preliminary activity with a manageable safety profile in patients with advanced non-urothelial carcinoma histology and urothelial carcinoma after previous chemotherapy exposure
- This deserves further evaluation of the combination that is ongoing with ARCADIA and other clinical trials
Presented by: Patrizia Giannatempo, MD, Instituto Nazionale dei Tumori, Milan, Italy
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2023 European Society of Medical Oncology (ESMO) Annual Meeting, Madrid, Spain, Fri, Oct 20 – Tues, Oct 24, 2023.