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
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.
