American Association for Cancer Research (AACR)
Clinical Cancer Research
,  volume 31 ,  issue 9 ,  pages OF1-OF10

Phase II trial of atezolizumab and bevacizumab for treatment of HPV-positive unresectable or metastatic squamous cell carcinoma of the anal canal

Jeffrey S. Morris 1, 2
, 
Suyu Liu 3, 4
, 
Kangyu Lin 2, 3
, 
Haifeng Zhu 1, 5
, 
Seema Prasad 2, 3
, 
Armeen Mahvash 6, 7
, 
Priya Bhosale 3, 7
, 
Baohua Sun 3, 8
, 
Edwin R. Parra 8, 9
, 
Ignacio Wistuba 3, 8
, 
Arjun Peddireddy 10, 11
, 
JAMES S. T. YAO 2, 12
, 
Julia Mendoza Perez 3, 8
, 
Mark Knafl 3, 5
, 
Scott E Woodman 3, 5
, 
C. Eng 13, 14
, 
Daniel T. Halperin 2, 15
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Boehringer Ingelheim (United States), Ridgefield, CT, United States | 
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Publication type: Journal Article
Publication date: 2025-02-28
American Association for Cancer Research (AACR)
scimago Q1
wos Q1
SJR: 4.800
CiteScore: 19.0
Impact factor: 10.2
ISSN: 10780432, 15573265
Abstract
Purpose:

Anti–PD-L1 antibodies are associated with responses in <25% of patients with metastatic human papillomavirus–associated malignancies. VEGF signaling causes immune evasion and immune suppression within the tumor. We evaluated the anti–PD-L1 antibody atezolizumab and anti-VEGF antibody bevacizumab for patients with unresectable, advanced anal cancer.

Patients and Methods:

For this phase II study, participants with previously treated, immunotherapy-naïve anal cancer received atezolizumab (1,200 mg) and bevacizumab (15 mg/kg) intravenously every 21 days. Responses were evaluated every 9 weeks (RECIST version 1.1). The primary endpoint was the best radiographic response. Median survival was estimated by Kaplan–Meier and compared for selected biomarkers (including paired pre- and on-treatment biopsies) using a log-rank test.

Results:

Among 20 participants, the overall response rate was 11% [95% confidence interval (CI): 1.2–32]. Median progression-free survival and overall survival were 4.1 months (95% CI, 2.6–not assessable) and 11.6 months (95% CI, 9.5–20), respectively. One grade 5 bevacizumab-related bowel perforation occurred. Analyses of 16 paired biopsies linked increases in IFN-γ (P = 0.03) and inflammatory response (P = 0.02) gene expression signatures with prolonged progression-free survival, as did increases in CD3+CD8+PD1+ (P = 0.02) cells and decreases in CD3+FoxP3+ cells (P = 0.04) from 10 paired biopsies with multiplex immunofluorescence. A subgroup of anal cancers characterized by the SBS31 “prior-platinum” signature demonstrated shorter median overall survival (HR, 6.3; 95% CI, 1.2–32; P = 0.01).

Conclusions:

Atezolizumab and bevacizumab demonstrate activity similar to anti–PD-1 antibodies alone for unresectable anal cancer. Our translational data identify undescribed chromosomal and transcriptomic biomarkers associated with survival for metastatic anal cancer. These correlative findings warrant confirmation and further validation in larger, prospective immunotherapy trials for advanced anal cancer.

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GOST |
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GOST Copy
Morris J. S. et al. Phase II trial of atezolizumab and bevacizumab for treatment of HPV-positive unresectable or metastatic squamous cell carcinoma of the anal canal // Clinical Cancer Research. 2025. Vol. 31. No. 9. p. OF1-OF10.
GOST all authors (up to 50) Copy
Morris J. S., Liu S., Lin K., Zhu H., Prasad S., Mahvash A., Bhosale P., Sun B., Parra E. R., Wistuba I., Peddireddy A., YAO J. S. T., Mendoza Perez J., Knafl M., Woodman S. E., Eng C., Halperin D. T. Phase II trial of atezolizumab and bevacizumab for treatment of HPV-positive unresectable or metastatic squamous cell carcinoma of the anal canal // Clinical Cancer Research. 2025. Vol. 31. No. 9. p. OF1-OF10.
RIS |
Cite this
RIS Copy
TY - JOUR
DO - 10.1158/1078-0432.ccr-24-1512
UR - https://aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-24-1512/752145/Phase-II-trial-of-atezolizumab-and-bevacizumab-for
TI - Phase II trial of atezolizumab and bevacizumab for treatment of HPV-positive unresectable or metastatic squamous cell carcinoma of the anal canal
T2 - Clinical Cancer Research
AU - Morris, Jeffrey S.
AU - Liu, Suyu
AU - Lin, Kangyu
AU - Zhu, Haifeng
AU - Prasad, Seema
AU - Mahvash, Armeen
AU - Bhosale, Priya
AU - Sun, Baohua
AU - Parra, Edwin R.
AU - Wistuba, Ignacio
AU - Peddireddy, Arjun
AU - YAO, JAMES S. T.
AU - Mendoza Perez, Julia
AU - Knafl, Mark
AU - Woodman, Scott E
AU - Eng, C.
AU - Halperin, Daniel T.
PY - 2025
DA - 2025/02/28
PB - American Association for Cancer Research (AACR)
SP - OF1-OF10
IS - 9
VL - 31
SN - 1078-0432
SN - 1557-3265
ER -
BibTex |
Cite this
BibTex (up to 50 authors) Copy
@article{2025_Morris,
author = {Jeffrey S. Morris and Suyu Liu and Kangyu Lin and Haifeng Zhu and Seema Prasad and Armeen Mahvash and Priya Bhosale and Baohua Sun and Edwin R. Parra and Ignacio Wistuba and Arjun Peddireddy and JAMES S. T. YAO and Julia Mendoza Perez and Mark Knafl and Scott E Woodman and C. Eng and Daniel T. Halperin},
title = {Phase II trial of atezolizumab and bevacizumab for treatment of HPV-positive unresectable or metastatic squamous cell carcinoma of the anal canal},
journal = {Clinical Cancer Research},
year = {2025},
volume = {31},
publisher = {American Association for Cancer Research (AACR)},
month = {feb},
url = {https://aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-24-1512/752145/Phase-II-trial-of-atezolizumab-and-bevacizumab-for},
number = {9},
pages = {OF1--OF10},
doi = {10.1158/1078-0432.ccr-24-1512}
}
MLA
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MLA Copy
Morris, Jeffrey S., et al. “Phase II trial of atezolizumab and bevacizumab for treatment of HPV-positive unresectable or metastatic squamous cell carcinoma of the anal canal.” Clinical Cancer Research, vol. 31, no. 9, Feb. 2025, pp. OF1-OF10. https://aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-24-1512/752145/Phase-II-trial-of-atezolizumab-and-bevacizumab-for.