Atezolizumab and Stereotactic Body Radiation in Metastatic, Recurrent, or Persistent Cervical Cancer: Results From a Phase 2 Multi-Institutional Study.

[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 AND MATERIALS] The study is designed as a prospective, phase II multi-institutional trial of stereotactic body radiation therapy (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.

[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.