Display options
Cite
Jain RK, Skelton Iv WP, Pond GR, et al. Angiotensin Blockade Modulates the Activity of PD1/L1 Inhibitors in Metastatic Urothelial Carcinoma. Clin Genitourin Cancer. 2021;19(6):540-546doi: 10.1016/j.clgc.2021.04.002.
Jain, R. K., Skelton Iv, W. P., Pond, G. R., Naqvi, M., Kim, Y., Curran, C., Freeman, D., Nuzzo, P. V., Alaiwi, S. A., Nassar, A. H., Jain, R. K., & Sonpavde, G. (2021). Angiotensin Blockade Modulates the Activity of PD1/L1 Inhibitors in Metastatic Urothelial Carcinoma. Clinical genitourinary cancer, 19(6), 540-546. https://doi.org/10.1016/j.clgc.2021.04.002
Jain, Rohit K, et al. "Angiotensin Blockade Modulates the Activity of PD1/L1 Inhibitors in Metastatic Urothelial Carcinoma." Clinical genitourinary cancer vol. 19,6 (2021): 540-546. doi: https://doi.org/10.1016/j.clgc.2021.04.002
Jain RK, Skelton Iv WP, Pond GR, Naqvi M, Kim Y, Curran C, Freeman D, Nuzzo PV, Alaiwi SA, Nassar AH, Jain RK, Sonpavde G. Angiotensin Blockade Modulates the Activity of PD1/L1 Inhibitors in Metastatic Urothelial Carcinoma. Clin Genitourin Cancer. 2021 Dec;19(6):540-546. doi: 10.1016/j.clgc.2021.04.002. Epub 2021 Apr 20. PMID: 34011489; PMCID: PMC8526625.
Copy Download .nbib Format: NLM
Share it on

Clin Genitourin Cancer. 2021 Dec;19(6):540-546. doi: 10.1016/j.clgc.2021.04.002. Epub 2021 Apr 20.

Angiotensin Blockade Modulates the Activity of PD1/L1 Inhibitors in Metastatic Urothelial Carcinoma.

Clinical genitourinary cancer

Rohit K Jain, William Paul Skelton Iv, Gregory Russell Pond, Mahrukh Naqvi, Youngchul Kim, Catherine Curran, Dory Freeman, Pier Vitale Nuzzo, Sarah Abou Alaiwi, Amin H Nassar, Rakesh K Jain, Guru Sonpavde

Affiliations

  1. H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
  2. Ontario Clinical Oncology Group, McMaster University, Hamilton, Ontario, Canada.
  3. Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA.
  4. Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Boston, USA.
  5. Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA. Electronic address: [email protected].

PMID: 34011489 PMCID: PMC8526625 DOI: 10.1016/j.clgc.2021.04.002

Abstract

BACKGROUND: The renin-angiotensin system is involved in the regulation of angiogenesis and cell proliferation. Angiotensin inhibition may improve drug delivery by enhancing tumor perfusion partly by downregulating transforming growth factor (TGF)-β. Because TGF-β is associated with resistance in patients with metastatic urothelial carcinoma (mUC) receiving programmed cell death protein 1/programmed cell death ligand 1 (PD1/L1) inhibitors, we hypothesized that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may enhance the outcomes of patients with mUC who receive PD1/L1 inhibitors.

PATIENTS AND METHODS: Data from patients with mUC who received PD1/L1 inhibitors as monotherapy were obtained; patients from the Dana-Farber Cancer Institute constituted the discovery dataset, and data from Moffitt Cancer Center served as the validation dataset. A logistic regression investigated the impact of concurrent ACEI/ARB primarily on any regression of tumor (ART) after controlling for prognostic factors.

RESULTS: Data were available for 178 patients from the discovery dataset, of whom 153 (86%) had received prior platinum and 33 (18.5%) concurrent ACEIs/ARBs. Multivariable logistic regression analysis revealed that ACEIs/ARBs were associated with greater probability of ART (odds ratio [OR] = 2.69; 95% confidence interval [CI], 1.15-6.30; P = .022). In the validation dataset, 101 patients were available, of whom 59 (58.4%) had received prior platinum and 22 (21.8%) concurrent ACEIs/ARBs. ACEI/ARB demonstrated a trend for association with ART (OR = 3.28; 95% CI, 0.98-10.99; P = .054) on multivariable analysis of the validation dataset.

CONCLUSIONS: Concurrent angiotensin blockade was associated with a higher rate of tumor regression in patients with mUC receiving PD1/L1 inhibitors. Validation is warranted in a prospective trial, especially given the cost efficacy of ACEIs/ARBs.

Copyright © 2021. Published by Elsevier Inc.

Keywords: Angiotensin receptor blockers; Angiotensin-converting enzyme; Immunotherapy; TGF-β; Urothelial carcinoma

Publication Types

Grant support