546 AtTEnd/ENGOT-EN7: phase III double-blind randomized placebo controlled trial of atezolizumab in combination with carboplatin and paclitaxel in women with advanced/recurrent endometrial carcinoma

Introduction/Background

The standard therapy for advanced/recurrent endometrial cancer includes carboplatin and paclitaxel (CP). Robust biological rationale suggested a synergy between immunotherapy and chemotherapy in this setting.

Methodology

AtTEnd is an academic study in advanced or recurrent endometrial carcinoma/carcinosarcoma patients with no prior systemic chemotherapy for recurrence. Patients were randomized (2:1 ratio) to receive either CP and atezolizumab or placebo, followed by atezolizumab or placebo until disease progression. The mismatch repair (MMR) status was evaluated centrally. Coprimary endpoints with a hierarchical approach were: progression free survival (PFS) in the deficient MMR (dMMR) population, PFS and overall survival (OS) in all comers.

Results

From Oct 2018 to Jan 2022 551 patients were enrolled across 10 countries (median follow-up 28.3 months). Of the 549 patients included in the intention to treat population, 125 (22.8%) had dMMR tumours and 352 (64.1%) had endometrioid carcinoma; 369 (67.2%) had recurrent disease and 148 (82.2%) of newly diagnosed cases had primary stage IV. In the dMMR population, the addition of atezolizumab showed a significant improved PFS (HR 0.36 95% CI:0.23–0.57; p=0.0005; median PFS: not reached vs. 6.9 months for atezolizumab vs placebo). The superiority in PFS was confirmed in all comers (HR 0.74 95%CI:0.61–0.91; p=0.0219; median PFS: 10.1 months vs 8.9 months for atezolizumab vs placebo). Interim analysis of OS in all comers indicated a trend in favor for atezolizumab, despite 45 (24.3%) placebo patients received immunotherapy as subsequent therapy. Duration of response in the dMMR population confirmed the efficacy of atezolizumab. Grade≥3 adverse events occurred in 66.9% and 63.8% of patients in atezolizumab vs placebo arm. Safety profile for CP + atezolizumab was manageable and consistent with expected toxicities.

Conclusion

The addition of atezolizumab to standard chemotherapy demonstrated a statistically significant improvement in PFS for patients with advanced/recurrent endometrial carcinomas with a substantial benefit in dMMR carcinomas.

Disclosures

The Mario Negri Institute for Pharmacological Research of Milan, Italy is the legal entity responsible for the governance, coordination, and execution of the study on behalf of Mario Negri Gynecologic Oncology (MaNGO) group. The study is funded by F. Hoffmann-La Roche Ltd. The trial protocol number is NCT03603184; 2018–001072-37.