Phase II Trial of Atezolizumab and Bevacizumab for Treatment of HPV-Positive Unresectable or Metastatic Squamous Cell Carcinoma of the Anal Canal

Q: What was the purpose of the phase II trial?

To evaluate atezolizumab plus bevacizumab for patients with unresectable, advanced anal cancer, given limited response rates to anti–PD-L1 therapy alone and VEGF-driven immune suppression in tumors.

Q: How were patients treated and how often were responses evaluated?

Participants received intravenous atezolizumab 1,200 mg and bevacizumab 15 mg/kg every 21 days, with radiographic responses assessed every 9 weeks using RECIST version 1.1.

Q: What were the key efficacy outcomes reported?

Across 20 participants, the overall response rate was 11%, with median progression-free survival of 4.1 months and median overall survival of 11.6 months, as summarized in the results.

Q: Which biomarkers were explored in the translational analyses?

The study analyzed associations between survival outcomes and gene expression and immune cell features from paired biopsies, including IFN-γ-related signals and changes in CD3+CD8+PD1+ and CD3+FoxP3+ cell populations.

Sep 23, 2026

Uploaded by James

Phase II study evaluates atezolizumab (anti–PD-L1) combined with bevacizumab (anti-VEGF) for patients with unresectable, advanced anal cancer linked to HPV. Anti–PD-L1 responses are reported in under 25% of metastatic HPV-associated malignancies, while VEGF activity promotes immune evasion. Eligible participants received intravenous atezolizumab 1,200 mg plus bevacizumab 15 mg/kg every 21 days; responses were assessed by RECIST 1.1, with progression and survival analyzed using Kaplan–Meier and log-rank testing. Results and translational biomarker analyses are summarized.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

AccessFree to download

Purpose

Patients and Methods

Results

Conclusions

Introduction

Phase II Trial of Atezolizumab and Bevacizumab for Treatment of HPV-Positive Unresectable or Metastatic Squamous Cell Carcinoma of the Anal Canal Van K. Morris1, Suyu Liu2, Kangyu Lin1, Haifeng Zhu3, Seema Prasad1, Armeen Mahvash4, Priya Bhosale4, Baohua Sun5, Edwin R. Parra5, Ignacio Wistuba5, Arjun Peddireddy6, James Yao1, Julia Mendoza-Perez5, Mark Knafl3, Scott E. Woodman3, Cathy Eng7, and Daniel Halperin1 | | | A | | B | S | | T | R | | A | | C | T | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Purpose: Anti–PD-L1 antibodies are associated with responsesin <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-na 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 progressionfree 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 ¼ 0.03) and inflammatory response (P ¼ 0.02) gene expression signatures with prolonged progression-free survival, as did increases in CD3+CD8+PD1+ (P ¼ 0.02) cells and decreases in CD3+FoxP3+ cells (P ¼ 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 ¼ 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. | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Introduction The incidence of squamous cell carcinoma of the anorectum continues to increase (1, 2) . Over the past two decades, the relative proportion of patients presenting with advanced or metastatic disease at the time of their initial diagnosis for anal cancer has steadily increased (3) . Mos

FAQs

What was the purpose of the phase II trial?

To evaluate atezolizumab plus bevacizumab for patients with unresectable, advanced anal cancer, given limited response rates to anti–PD-L1 therapy alone and VEGF-driven immune suppression in tumors.

How were patients treated and how often were responses evaluated?

Participants received intravenous atezolizumab 1,200 mg and bevacizumab 15 mg/kg every 21 days, with radiographic responses assessed every 9 weeks using RECIST version 1.1.

What were the key efficacy outcomes reported?

Across 20 participants, the overall response rate was 11%, with median progression-free survival of 4.1 months and median overall survival of 11.6 months, as summarized in the results.

Which biomarkers were explored in the translational analyses?

The study analyzed associations between survival outcomes and gene expression and immune cell features from paired biopsies, including IFN-γ-related signals and changes in CD3+CD8+PD1+ and CD3+FoxP3+ cell populations.

Sep 23, 2026

Uploaded by James