A randomized phase III trial of platinum chemotherapy plus paclitaxel with bevacizumab and atezolizumab versus platinum chemotherapy plus paclitaxel and bevacizumab in metastatic (stage IVB), persistent, or recurrent carcinoma of the cervix: the BEATcc study (ENGOT-Cx10/GEICO 68-C/JGOG1084/GOG-3030)

Abstract

Background: Patients with metastatic, recurrent, or persistent cervical cancer not amenable to local control and/or distant metastases have a very poor prognosis, only being candidates for palliative-systemic therapy. First line standard treatment in this scenario is based on cisplatin/paclitaxel plus bevacizumab (GOG 240 regimen) with a short median overall survival (16.8 months) and progression-free survival (8.2 months).

Primary objective: To determine whether the addition of atezolizumab to cisplatin-paclitaxel and bevacizumab improves overall survival, compared with cisplatin-paclitaxel plus bevacizumab in patients with metastatic, recurrent, or persistent cervical cancer.

Study hypothesis: The primary hypothesis is whether the addition of atezolizumab to cisplatin-paclitaxel and bevacizumab improves overall survival in metastatic, recurrent, or persistent cervical cancer.

Trial design: The BEATcc study is a phase III, randomized, open-label, multi-center clinical trial. The study will be performed on an intent-to-treat population. The control arm is the administration of chemotherapy (platinum plus paclitaxel) and bevacizumab, while the experimental arm is the administration of atezolizumab in combination with the same chemotherapy regimen (1:1 randomization). The trial will be run under the ENGOT umbrella alongside JGOG and GOG-F. GEICO is the lead group on behalf of ENGOT.

Major inclusion/exclusion criteria: Women over 18 years old with histologically or cytologically confirmed diagnosis of squamous cell carcinoma, adenocarcinoma, or adenosquamous metastatic, recurrent, or persistent cervical cancer, not amenable for curative treatment with surgery and/or radiation therapy, will be included. Women are not eligible if they have received prior systemic anti-cancer therapy for metastatic or persistent/recurrent disease or they have disease involving the bladder or rectum at the screening/baseline pelvic magnetic resonance imaging.

Primary endpoint: Overall survival, defined as the observed length of life from entry into the study (day of randomization) to death from any cause or the date of last contact.

Sample size: A total of 404 patients are expected to be recruited into the study, assuming a total 10% drop-out rate. In order to test whether the experimental arm improves overall survival, the study will have 80% power using one-sided α of 0.025. There will be one interim analysis to close the study in case of early efficacy results in the experimental arm.

Estimated dates for completing accrual and presenting results: The trial was launched in Q3 2018 and the trial is estimated to close in Q3 2022. We expect to be able to report mature data from the BEATcc trial by 2023.

Trial registration: ClinicalTrials.gov (NCT03556839).

Keywords: cervical cancer.