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A phase II trial of durvalumab and tremelimumab in metastatic, non-urothelial carcinoma of the urinary tract

Background: Immune checkpoint blockade has made a significant impact on the clinical outcomes of patients with metastatic urothelial carcinoma (UC). However, evidence for this approach in patients with non-UC of the urinary tract is limited.

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

  1. Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
  2. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
  3. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
  4. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
  5. Weill Cornell Medical College, New York, NY, USA
  6. 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.

Read an Expert Commentary by Bishoy Faltas, MD