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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MSK Authors
  1. Joshua Chaim
    34 Chaim
  2. Dean Bajorin
    604 Bajorin
  3. Gopakumar Vasudeva Iyer
    235 Iyer
  4. Achim Jungbluth
    423 Jungbluth
  5. Ashley Regazzi
    67 Regazzi
  6. Jonathan Eric Rosenberg
    408 Rosenberg
  7. Chung-Han   Lee
    109 Lee
  8. Samuel Aaron Funt
    89 Funt
  9. Asia S McCoy
    16 McCoy
  10. Min Yuen   Teo
    72 Teo
  11. Karissa A. Whiting
    20 Whiting
  12. Vanessa A Peters
    2 Peters