According to the manufacturer’s recent statement, the combination of durvalumab and tremelimumab did not lead to an increase in overall survival (OS) in patients undergoing treatment with stage IV unresectable bladder cancer. In addition, durvalumab monotherapy also did not demonstrate OS compared to standard chemotherapy in patients with high expression of PD-L1.
DANUBE is a phase III, multicenter study (220 institutions among 24 countries) that recruited just over 1000 virgin individuals of cancer treatment with documented histological or cytological confirmation of urothelium transition cell carcinoma with unresectable presentation, or stage IV. With 1: 1: 1 randomization, patients were allocated to receive the immunotherapy combination previously mentioned, durvalumab monodroga or standard platinum-based chemotherapy according to cisplatin eligibility (cisplatin and gemcitabine or carboplatin and gemcitabine).
The co-primary enpoints of the clinical trial were OS for combination of durvalumab with tremelimumab compared to platinum-based chemotherapy in the total population and OS for durvalumab monotherapy compared to the same control arm in patients with high expression of PD-L1 (defined as> 25 % expression in infiltrating tumor or immune cells). All patients were followed up for a period of 2 years.
Secondary objectives of this study include progression-free survival (PFS) in the total population with combined immunotherapy, PFS of durvalumab monotherapy in patients with high expression of PD-L1, response rate in the total population of combination therapy in comparison with the platinum-based chemotherapy group and comparison of single-drug durvalumab RT with chemotherapy. Response duration, safety, quality of life and pharmacokinetics analyzes were also performed.