As reported in The Lancet Oncology by Nicoletta Colombo, MD, and colleagues, the phase III AtTEnd trial showed improved progression-free survival with the addition of atezolizumab to chemotherapy in patients with recurrent or advanced endometrial cancer, particularly among those with mismatch repair–deficient (dMMR) tumors.
![Nicoletta Colombo, MD](/media/14018164/5-colombo.jpg)
Nicoletta Colombo, MD
Study Details
The double-blind trial included 549 eligible patients from sites across Europe, Australia, New Zealand, and Asia. They were randomly assigned 2:1 between October 2018 and January 2022 to receive atezolizumab at 1,200 mg (n = 360) or placebo (n = 189) with carboplatin at an AUC of 5 or 6 and paclitaxel at 175 mg/m² on day 1 every 21 days for six to eight cycles, followed by atezolizumab or placebo every 21 days until disease progression or unacceptable toxicity. The co-primary endpoints were progression-free survival (in patients with dMMR tumors and in the overall population) and overall survival (in the overall population).
Progression-Free Survival
Median follow-up was 28.3 months (interquartile range = 21.2–37.6 months).
dMMR disease was present in 81 patients (23%) in the atezolizumab group and 44 patients (23%) in the control group. In the primary analysis of progression-free survival, median progression-free survival among patients with dMMR disease was not estimable (95% confidence interval [CI] = 12.4 months to not estimable) in the atezolizumab group vs 6.9 months (95% CI = 6.3–10.1 months) in the control group (hazard ratio [HR] = 0.36, 95% CI = 0.23–0.57, P = .0005). In the overall population, median progression-free survival was 10.1 months (95% CI = 9.5–12.3 months) in the atezolizumab group vs 8.9 months (95% CI = 8.1–9.6 months) in the control group (HR = 0.74, 95% CI = 0.61–0.91, P = .022).
In an interim analysis of all patients, median overall survival was 38.7 months (95% CI = 30.6 months to not estimable) in the atezolizumab group vs 30.2 months (95% CI = 25.0–37.2 months) in the control group (HR = 0.82, 95% CI = 0.63–1.07, P = .048). Survival follow-up is ongoing.
Adverse Events
Grade ≥ 3 adverse events occurred in 67% of those in the atezolizumab group vs 64% of those in the control group; the most common adverse events were neutropenia (27% vs 28%), anemia (14% vs 13%), leukopenia (9% vs 3%), thrombocytopenia (8% vs 8%), and febrile neutropenia (6% vs 4%). Grade ≥ 3 adverse events considered related to treatment were reported in 26% vs 14% of patients. Serious adverse events occurred in 37% vs 34% of patients and were considered treatment-related in 13% vs 3%. Adverse events led to death in 11 patients (3%) in the atezolizumab group and 4 patients (2%) in the control group; one death in each group (from pneumonia in both patients) was considered to be related to treatment.
The investigators concluded: “Atezolizumab plus chemotherapy increased progression-free survival in patients with advanced or recurrent endometrial carcinoma, particularly in those with dMMR carcinomas, suggesting the addition of atezolizumab to standard chemotherapy as first-line treatment in this specific subgroup.”
Elena Biagioli, MSc, of the Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy, is the corresponding author of The Lancet Oncology article.
Disclosure: The study was funded by F. Hoffmann–La Roche. For full disclosures of the study authors, visit thelancet.com.