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

• Published in: Cancer medicine (Malden, MA) MA), 2021-02, Vol.10 (3), p.1074-1083
• Main Authors: Sarfaty, Michal, Whiting, Karissa, Teo, Min Yuen, Lee, Chung‐Han, Peters, Vanessa, Durocher, Jennifer, Regazzi, Ashley M., McCoy, Asia S., Hettich, Grace, Jungbluth, Achim A., Al‐Ahmadie, Hikmat, Ostrovnaya, Irina, Chaim, Joshua, Bajorin, Dean F., Rosenberg, Jonathan E., Iyer, Gopa, Funt, Samuel A.
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Adverse events; Bladder; Bladder cancer; Cancer therapies; Chemotherapy; Clinical Cancer Research; Histology; Immune checkpoint; Immunotherapy; Liver; Lymphatic system; Metastases; Metastasis; Monoclonal antibodies; Original Research; Patients; PD-L1 protein; Response rates; small cell carcinoma; Squamous cell carcinoma; Targeted cancer therapy; Tumors; Urinary tract; Urothelial carcinoma; variant histology
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.3699

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 follow‐up 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. Metastatic, non‐UC tumors of the urinary tract have an aggressive clinical course and dismal prognosis. This phase II trial evaluating durvalumab and tremelimumab demonstrated a manageable safety profile but lack of clinical activity.