Methods: This was a phase II open-label study of durvalumab 1500 mg and tremelimumab 75 mg every 4 weeks for four cycles followed by durvalumab 1500 mg every 4 weeks. Eligible patients had metastatic non-UC with ECOG PS 0–1 regardless of prior therapy (except small cell carcinoma who were pretreated). The primary endpoint was overall response rate per RECIST v1.1. A Simon's minimax two-stage design was employed, with 13 patients planned for stage one. Pre-treatment tumors underwent PD-L1 staining and next-generation sequencing.
Results: Thirteen patients were treated, including seven small cell carcinoma, three squamous cell carcinoma, and three adenocarcinoma. Eleven patients had visceral metastases. No responses were observed; 11 patients had PD and 2 patients had SD. Median PFS was 1.8 months (95% CI, 1.25-not reached [NR]) with a median followup of 7.38 months (range, 5.23–21.99 months). Median OS was 6.97 months (95% CI, 4.34-NR). One patient's tumor was PD-L1 positive and all sequenced tumors (n = 8) were microsatellite stable. Grades 3–4 treatment-related adverse events occurred in 38.4% of patients.
Conclusions: In a poor prognosis cohort of patients with non-UC, durvalumab and tremelimumab lacked clinical activity while demonstrating a manageable safety profile.
Michal Sarfaty,1,6 Karissa Whiting,2 Min Yuen Teo,1,5 Chung-Han Lee,1,5 Vanessa Peters,1 Jennifer Durocher,1 Ashley M. Regazzi,1 Asia S. McCoy,1 Grace Hettich,1 Achim A. Jungbluth,3 Hikmat Al-Ahmadie,3 Irina Ostrovnaya,2 Joshua Chaim,4 Dean F. Bajorin,1,5 Jonathan E. Rosenberg,1,5 Gopa Iyer,1,5 Samuel A. Funt,1,5
- Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Weill Cornell Medical College, New York, NY, USA
- Davidoff Cancer Center, Petah-Tikva, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
Source: Sarfaty M, Whiting K, Teo MY et al. "A phase II trial of durvalumab and tremelimumab in metastatic, non‐urothelial carcinoma of the urinary tract." Cancer Medicine. 2021. 10, 3, 1074-1083.