Atezolizumab and stereotactic body radiation in metastatic, recurrent, or persistent cervical cancer: Results from a phase II multi-institutional study.

5536 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. Secondary endpoints included overall response, progression free survival (PFS), overall survival (OS), and adverse events. Clinical trial information: NCT03614949. 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 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 – 54) with a 6-month OS of 76%. No differences were noted in OS or PFS by PD-L1 status. 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. Clinical trial information: NCT03614949 .