As reported in The Lancet Oncology by Sandro Pignata, MD, and colleagues, the Italian phase II MITO END-3 trial showed no progression-free survival benefit with the addition of first-line avelumab to carboplatin/paclitaxel in patients with advanced or recurrent endometrial cancer. A trend toward benefit was observed in the subgroup of patients with mismatch repair–deficient (dMMR) disease.

Sandro Pignata, MD

Study Details

The open-label multicenter trial included 125 patients with no prior systemic therapy as primary treatment for advanced or metastatic disease. They were randomly assigned between April 2018 and May 2021 to receive carboplatin at area under the curve = 5 and paclitaxel at 175 mg/m² every 3 weeks for six to eight cycles (n = 62), or avelumab at 10 mg/kg added to carboplatin/paclitaxel every 3 weeks and then every 2 weeks as single maintenance treatment after the end of chemotherapy until disease progression or unacceptable toxicity (n = 63).  

The primary endpoint was investigator-assessed progression-free survival in the intent-to-treat population.

Progression-Free Survival

Median follow-up was 23.3 months (interquartile range = 13.2–29.6 months). Median progression-free survival was 9.9 months (95% confidence interval [CI] = 6.7–12.1 months) in the control group vs 9.6 months (95% CI = 7.2–17.7 months) in the avelumab group (hazard ratio [HR] = 0.78, 60% CI = 0.65–0.93, P = .085).

Mismatch repair (MMR) status was known for 101 patients. Among patients with dMMR disease, median progression-free survival was not reached (95% CI = 8.9 to not evaluable) among 26 patients in the avelumab group vs 8.0 months (95% CI = 4.8–12.3 months) among 32 patients in the control group (HR = 0.41, 95% CI = 0.14–1.18). Among patients with MMR-proficient disease, median progression-free survival was 8.3 months (95% CI = 6.2–10.8 months) among 35 in the avelumab group vs 10.8 months (95% CI = 6.0–17.4 months) among 29 in the control group (HR = 1.17, 95% CI = 0.65–2.10).

Adverse Events

A total of 24 serious adverse events were observed in the avelumab group vs 7 events in the control group. The most common grade 3 or 4 adverse event was decreased neutrophils, occurring in 31% of patients in the avelumab group vs 43% of the control group. Serious adverse events led to death in two patients in the avelumab group; one death was due to respiratory failure following severe myositis (considered possibly related to treatment) and one was due to cardiac arrest (not related to treatment).

The investigators concluded, “Adding avelumab to first-line chemotherapy deserves further testing in patients with advanced or recurrent endometrial cancer, although consideration of MMR status is warranted.”

Dr. Pignata, of Istituto Nazionale Tumori, IRCCS, “Fondazione G. Pascale,” Naples, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by Pfizer. For full disclosures of the study authors, visit thelancet.com.