210 - Atezolizumab and Stereotactic Body Radiation in Metastatic, Recurrent, or Persistent Cervical Cancer: Long Term Results and Biomarker Analysis from a Phase II Multi-Institutional Study
Presenter(s)
K. A. Ahmed1, A. M. Quick2, H. S. Chon3, S. Kim4, M. Wang5, Y. Kim6, J. Y. Chern7, K. Bixel8, M. E. Montejo9, R. Dowell3, D. C. Fernandez9, C. Lam3, A. Hakam10, M. Shafique11, M. M. Shahzad7, and R. M. Wenham12; 1H. Lee Moffitt Cancer Center and Research Institute, Department of Radiation Oncology, Tampa, FL, 2Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, 3Moffitt Cancer Center, Tampa, FL, 4Mayo Clinic, Jacksonville, FL, 5Taipei Veterans Hospital, Taipei City, Taiwan, 6H. Lee Moffitt Cancer Center and Research Institute, Department of Bioinformatics and Biostatistics, Tampa, FL, 7H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 8Stanford University, Palo Alto, CA, 9Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 10H. Lee Moffitt Cancer Center and Research Institute, Department of Pathology, Tampa, FL, 11Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 12H. Lee Moffitt Cancer Center and Research Institute, Department of Gynecologic Oncology, Tampa, FL
Purpose/Objective(s): Response rates to single agent anti-PD-1/PD-L1 therapy for metastatic cervical cancer have been modest with limited responses noted in PD-L1 negative tumors. Stereotactic body radiation therapy (SBRT) has a well-defined role in the management of oligometastatic disease. There may be potential synergy between stereotactic radiation and anti-PD-1/PD-L1 checkpoint inhibition in advanced cervical cancer. A prospective, phase II multi-institutional trial of SBRT followed by atezolizumab in the management of metastatic cervical cancer was conducted. Long-term follow-up is reported with correlative blood analyses.
Materials/Methods: SBRT was delivered to a site metastases followed one week later by atezolizumab (1200 mg intravenously q3 weeks). Key eligibility criteria included patients with metastatic, recurrent, or persistent cervical cancer with at least 2 distinct lesions. The primary outcome was objective response rate measured at the unirradiated target lesion. Secondary endpoints included overall response, progression free survival (PFS), overall survival (OS), and adverse events. Blood was collected at baseline and q3 weeks for flow cytometry and plasma cytokine assessment. Clinical trial information: NCT03614949.
Results: A total of 21 patients were enrolled. Median follow-up is 45.6 months. The majority of patients had PD-L1 negative tumors (n=15; 71%) and adenocarcinoma (n=10; 48%) with a median of 2 (range: 1-5) prior lines of therapy. An objective response at the unirradiated target lesion was observed in 8 patients (38%), meeting the study defined endpoint with responses noted in PD-L1 negative tumors. The best overall response was a partial response in 5 (24%) and stable disease in 12 (57%) patients. The median PFS was 4.7 months (95% CI: 3.9- 7.4) with a 6-month PFS of 48%. The median OS was 26 months (95% CI 7.6 – 46) with a 6-month OS of 76%. Exploratory analysis revealed lower levels of CD4 Treg and higher levels of CD8 T effector cells (p=0.03) at baseline were associated with improved response. In addition, higher levels of CD4T-223 (LAG-3), were noted to be associated with poor response (p=0.04). Higher levels of baseline pro-inflammatory cytokines including GM-CSF, INF-gamma, IL7, IL9, and MIP-1b/CCL4 were noted in patients with an objective response (p < 0.05).
Conclusion: In this long-term analysis of SBRT and atezolizumab in metastatic cervical cancer, combination therapy may have allowed for improved response rates to immune checkpoint inhibition particularly in PD-L1 negative tumors. Circulating systemic biomarkers were found to be associated with clinical outcomes.