Atezolizumab plus bevacizumab and chemotherapy for metastatic, persistent, or recurrent cervical cancer (BEATcc): a randomised, open-label, phase 3 trial

Background: The GOG240 trial established bevacizumab with chemotherapy as standard first-line therapy for metastatic or recurrent cervical cancer. In the BEATcc trial (ENGOT-Cx10–GEICO 68-C–JGOG1084–GOG-3030), we aimed to evaluate the addition of an immune checkpoint inhibitor to this standard backbone. Methods: In this investigator-initiated, randomised, open-label, phase 3 trial, patients from 92 sites in Europe, Japan, and the USA with metastatic (stage IVB), persistent, or recurrent cervical cancer that was measurable, previously untreated, and not amenable to curative surgery or radiation were randomly assigned 1:1 to receive standard therapy (cisplatin 50 mg/m² or carboplatin area under the curve of 5, paclitaxel 175 mg/m², and bevacizumab 15 mg/kg, all on day 1 of every 3-week cycle) with or without atezolizumab 1200 mg. Treatment was continued until disease progression, unacceptable toxicity, patient withdrawal, or death. Stratification factors were previous concomitant chemoradiation (yes vs no), histology (squamous cell carcinoma vs adenocarcinoma including adenosquamous carcinoma), and platinum backbone (cisplatin vs carboplatin). Dual primary endpoints were investigator-assessed progression-free survival according to Response Evaluation Criteria in Solid Tumours version 1.1 and overall survival analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT03556839, and is ongoing. Findings: Between Oct 8, 2018, and Aug 20, 2021, 410 of 519 patients assessed for eligibility were enrolled. Median progression-free survival was 13·7 months (95% CI 12·3–16·6) with atezolizumab and 10·4 months (9·7–11·7) with standard therapy (hazard ratio [HR]=0·62 [95% CI 0·49–0·78]; p<0·0001); at the interim overall survival analysis, median overall survival was 32·1 months (95% CI 25·3–36·8) versus 22·8 months (20·3–28·0), respectively (HR 0·68 [95% CI 0·52–0·88]; p=0·0046). Grade 3 or worse adverse events occurred in 79% of patients in the experimental group and in 75% of patients in the standard group. Grade 1–2 diarrhoea, arthralgia, pyrexia, and rash were increased with atezolizumab. Interpretation: Adding atezolizumab to a standard bevacizumab plus platinum regimen for metastatic, persistent, or recurrent cervical cancer significantly improves progression-free and overall survival and should be considered as a new first-line therapy option. Funding: F Hoffmann-La Roche.