Atezolizumab and Stereotactic Body Radiation Therapy in Metastatic, Recurrent or Persistent Cervical Cancer: Interim Results from a Non-Randomized, Open-Label Phase II Multi-Institutional Study

Abstract

<h3>Purpose/Objective(s)</h3> Inhibition of the anti-PD-1/PD-L1 axis has been approved in the metastatic, recurrent, or persistent settings for cervical cancer. 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. We hypothesize treatment with atezolizumab and SBRT will be well tolerated and may improve tumor control rates compared to atezolizumab alone in the management of metastatic, recurrent, or persistent cervical cancer. <h3>Materials/Methods</h3> The study is designed as a prospective, single arm, nonrandomized, open-label, phase II multi-institutional trial of SBRT with 24 Gy in 3 fractions to patients with ≥ 2 metastatic sites followed 1 week later by atezolizumab (1200 mg IV every 3 weeks) for patients with recurrent, persistent, or metastatic cervical cancer. The primary objective of the study is to evaluate the objective response rate by immune-related response evaluation criteria in solid tumors (irRECIST) criteria following SBRT and atezolizumab at the unirradiated target lesion. Secondary endpoints include progression free survival (PFS), overall survival (OS), and adverse events. Results of the pre-planned interim analysis are reported. Clinical trial information: NCT03614949. <h3>Results</h3> Between January 2019 and September 2021, a total of 13 patients were enrolled. The majority of patients had adenocarcinoma (n=9; 69%) with a median age of 50 (range: 36-69). Median number of lines of prior therapy was 2 (range: 1-5). Median follow-up is 18 months (range: 2.7-35.8 months). The median PFS was 4.5 months (95% CI: 3.87- Not reached) with a 6-month PFS of 46%. The median OS was 11 months (95% CI 7.77 – Not reached) with a 6-month OS of 84%. The overall response (irRECIST) was a partial response in 3 (23%) and stable disease in 4 (31%) patients. An objective response was observed in 2 patients meeting criteria to move to the stage II portion of the trial. Study therapy was well tolerated with no patients discontinuing therapy due to side effects. The most common grade ≥2 toxicities at least possibly attributed to study therapy included lymphopenia (n=4; 31%), fatigue (n=3; 23%), and hypothyroidism (n=2; 15%). <h3>Conclusion</h3> Atezolizumab and SBRT was well tolerated in the first stage of the phase II trial. Objective responses were noted in two patients meeting the pre-planned criteria to warrant opening of the second stage of the study.