A phase II trial of durvalumab and tremelimumab in metastatic, non-urothelial carcinoma of the urinary tract Journal Article
| Authors: | Sarfaty, M.; Whiting, K.; Teo, M. Y.; Lee, C. H.; Peters, V.; Durocher, J.; Regazzi, A. M.; McCoy, A. S.; Hettich, G.; Jungbluth, A. A.; Al-Ahmadie, H.; Ostrovnaya, I.; Chaim, J.; Bajorin, D. F.; Rosenberg, J. E.; Iyer, G.; Funt, S. A. |
| Article Title: | A phase II trial of durvalumab and tremelimumab in metastatic, non-urothelial carcinoma of the urinary tract |
| Abstract: | 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. © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. |
| Keywords: | squamous cell carcinoma; adenocarcinoma; immunotherapy; urothelial carcinoma; small cell carcinoma; variant histology |
| Journal Title: | Cancer Medicine |
| Volume: | 10 |
| Issue: | 3 |
| ISSN: | 2045-7634 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2021-02-01 |
| Start Page: | 1074 |
| End Page: | 1083 |
| Language: | English |
| DOI: | 10.1002/cam4.3699 |
| PUBMED: | 33382520 |
| PROVIDER: | scopus |
| PMCID: | PMC7897955 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 April 2021 -- Source: Scopus |
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