Atezolizumab and Stereotactic Body Radiation in Metastatic, Recurrent, or Persistent Cervical Cancer: Results from a Phase II Multi-Institutional Study.

Abstract

Background: Pembrolizumab is approved for PD-L1+ but not PD-L1 negative metastatic, recurrent, or persistent cervical cancer. Response rates to single agent anti-PD-1/PD-L1 therapy have been modest with no responses noted in PD-L1 negative tumors.

Methods: The study is designed as a prospective, phase II multi-institutional trial of SBRT followed 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 objective was objective response rate measured at the unirradiated target lesion.

Clinical trial information: NCTXX.

Results: A total of 21 patients were enrolled. Median follow-up is 23.6 months. The majority of patients had adenocarcinoma (n=10; 48%) and were PD-L1 negative (n=15; 71%). The best overall response was a partial response in 5 (24%) and stable disease in 12 (57%) patients. The median duration of response was 8.6 months (95% CI: 4.5-13.6 months). An objective response at the unirradiated target lesion was observed in 8 patients (38%), meeting the study defined endpoint. Responses were noted in PD-L1 negative tumors. The most common grade ≥ 2 toxicities at least possibly attributed to study therapy included lymphopenia (n=6; 29%), nausea/vomiting (n=3; 14%), and hyponatremia (n=3; 14%).

Conclusions: In this first trial of SBRT and atezolizumab in metastatic cervical cancer unselected for PD-L1, combination therapy was well tolerated. Responses were noted in PD-L1 negative tumors. Combination therapy may allow for improved response rates to immune checkpoint inhibition in metastatic cervical cancer particularly in PD-L1 negative tumors.