The addition of atezolizumab (Tecentriq) to standard chemotherapy demonstrated noninferior survival compared with placebo plus chemotherapy in patients with advanced or recurrent endometrial cancer, according to final results from the phase 3 AtTEnd/ENGOT-EN7 trial presented at the European Society of Medical Oncology (ESMO) Congress 2025.
After a median follow-up of 48.9 months, the overall survival analysis showed a nonsignificant difference between patients treated with atezolizumab versus placebo, with median survival of 36.0 months (95% CI, 30.0-45.2) versus 30.5 months (95% CI, 25.0-41.8), respectively. The 12- and 24-month OS rates were 80.1% versus 73.8% and 61.1% versus 58.4% (HR, 0.87; 95% CI, 0.69-1.10; P = .0824).
Significant Benefits in dMMR Subgroup
In a planned subgroup analysis based on mismatch repair deficient (dMMR) status, patients with dMMR disease experienced significantly improved overall survival outcomes with atezolizumab. After a median follow-up of 49.1 months, the median OS was not evaluable (95% CI, 60.9-NE) in the atezolizumab arm versus 31.8 months (95% CI, 13.5-47.0) in the placebo arm. The 12- and 24-month survival rates were 86.8% versus 66.8% and 74.8% versus 54.8% (HR, 0.49; 95% CI, 0.28-0.83; P = .0038).
"The addition of atezolizumab to chemotherapy did not demonstrate a statistically significant survival benefit in patients with advanced or recurrent endometrial carcinoma," said Maria Pilar Barretina Ginesta, MD, associate professor of the Medical Sciences Department of Girona University. "In the pre-planned subgroup analysis based on MMR status, a substantial survival improvement was observed in patients with dMMR carcinomas."
Among patients with non-dMMR status, survival outcomes did not significantly differ between the two regimens. The median OS was 30.0 months (95% CI, 23.8-37.4) with atezolizumab versus 30.2 months (95% CI, 22.4-40.7) with placebo, and the 12- and 24-month rates were 77.8% versus 75.8% and 55.9% versus 58.8%, respectively (HR, 1.02; 95% CI, 0.78-1.34; P = .6644).
Progression-Free Survival Benefits
Across all patients, progression-free survival outcomes numerically favored atezolizumab. The median PFS was 9.9 months (95% CI, 9.3-12.0) versus 8.9 months (95% CI, 8.1-9.6), with 12- and 24-month rates of 44.7% versus 28.9% and 28.7% versus 16.8% (HR, 0.70; 95% CI, 0.58-0.86; P = .0055). A non-proportional hazards restricted mean survival time difference of 2.52 months (95% CI, 0.82-4.22) at 30 months was observed.
Among patients with dMMR disease, atezolizumab exhibited enhanced PFS outcomes versus placebo. The median PFS was not evaluable (95% CI, 12.3-NE) versus 6.9 months (95% CI, 6.2-9.0), with 12- and 24-month PFS rates of 62.7% versus 23.3% and 52.1% versus 16.3% (HR, 0.35; 95% CI, 0.22-0.55; P = .0002).
For patients with non-dMMR status, noninferior PFS was observed with atezolizumab. The median PFS was 9.5 months (95% CI, 9.0-10.4) with atezolizumab versus 9.2 months (95% CI, 8.5-9.9) with placebo, with PFS rates of 39.1% versus 30.2% at 12 months and 21.7% versus 16.0% at 24 months (HR, 0.86; 95% CI, 0.69-1.08; P = .1885).
Response Rates and Duration
The objective response rate and duration of response among patients with dMMR status numerically favored the atezolizumab arm. The ORR with atezolizumab was 82.4% (95% CI, 71.4%-89.7%) with a complete response rate of 26.5% and a partial response rate of 55.9%, compared to 75.7% (95% CI, 56.3%-84.7%) with placebo, which had a CR rate of 18.9% and a PR rate of 56.8%.
Regarding duration of response, the median values were not evaluable (95% CI, 15.0-NE) with atezolizumab versus 4.9 months (95% CI, 4.3-8.4) with placebo, with 12- and 24-month rates of 66.9% versus 22.3% and 57.6% versus 14.8% (HR, 0.26; 95% CI, 0.15-0.47).
In the non-dMMR population, noninferior ORR and DOR outcomes with atezolizumab were observed. The ORR was 75.6% (95% CI, 65.3%-77.0%) with CR and PR rates of 15.1% and 60.5% versus 74.6% (95% CI, 61.9%-78.1%) with CR and PR rates of 10.5% and 64.0% with placebo.
Study Design and Patient Characteristics
The phase 3 study enrolled patients with advanced newly diagnosed or recurrent endometrial carcinoma or carcinosarcoma and randomly assigned them 2:1 to receive paclitaxel at 175 mg/m² and carboplatin area under the curve 5 or 6 with 1200 mg of atezolizumab or matching placebo. Following chemotherapy, patients received 1200 mg of atezolizumab as maintenance or matching placebo.
Among all patients in the atezolizumab (n = 360) and placebo arms (n = 189), 22.5% versus 23.3% had dMMR status. Additionally, 67.5% versus 66.7% had recurrent disease status, and 70.6% versus 68.2% did not receive previous chemotherapy. The median age was 67 years (range, 30-89) versus 65 years (range, 30-89), and most patients were Caucasian (80.3% versus 75.7%), had PD-L1–negative disease (68.6% versus 68.2%), and had intact ARID1A expression (68.9% versus 69.3%).
Safety Profile
Any-grade adverse effects occurred in 98.6% versus 100% of patients in the atezolizumab and placebo arms, respectively, with those related to atezolizumab versus placebo occurring in 75.8% versus 63.8%. Grade 3 or higher AEs were observed in 26.4% versus 14.1% of the respective arms, and fatal AEs related to either agent occurred in 0.3% versus 0.5% of patients.
The most common adverse effects in the atezolizumab and placebo arms were anemia (41.3% versus 35.1%), fatigue (39.0% versus 41.1%), neutropenia (40.7% versus 39.5%), peripheral sensory neuropathy (38.8% versus 39.5%), nausea (34.0% versus 37.3%), and alopecia (31.5% versus 36.2%).
