WES-Aneuploidy Scores Predict Immunotherapy Response in dMMR Endometrial Cancer
Biomarker Analysis of the AtTEnd Trial: Key Findings
Here’s a breakdown of the key findings from the biomarker analysis of the AtTEnd trial, focusing on the W-AS (Wnt Activation Score) biomarker:
Key Takeaways:
* dMMR Population: In patients with deficient mismatch repair (dMMR) endometrial cancer, high W-AS was associated with poorer outcomes (PFS and OS) when atezolizumab was added to chemotherapy compared to placebo plus chemotherapy.This suggests a subset of dMMR patients may not benefit from immunotherapy.
* Prevalence of High W-AS: High W-AS was found in 9.1% of patients with endometrial cancer in the dMMR population.
* Low W-AS Benefit: Patients with low W-AS in the dMMR population showed a important OS benefit with atezolizumab (HR 0.40, P =.0043). Median OS was not estimable (NE) with atezolizumab vs 37.2 months with placebo.
* High W-AS No Benefit: Patients with high W-AS in the dMMR population did not show a significant OS benefit with atezolizumab (HR 1.36, P = .7238). Median OS was 11.2 months with atezolizumab vs 31.8 months with placebo.
* Ongoing Analysis: Analysis of the non-dMMR population is still underway.
* Potential Predictive Biomarker: Researchers believe W-AS may identify approximately 10% of dMMR endometrial cancer patients who do not benefit from adding immunotherapy to chemotherapy. Though, they emphasize the need for validation in larger cohorts.
About the AtTEnd Trial:
* Design: A phase 3, multicenter, double-blind, randomized, placebo-controlled trial.
* participants: Patients with advanced or recurrent endometrial carcinoma or carcinosarcoma (nonetheless of MMR status).
* Treatment: Atezolizumab + chemotherapy vs. placebo + chemotherapy.
* Previous Findings: The trial previously showed a significant advancement in Progression-Free Survival (PFS) with the addition of atezolizumab (HR 0.36, P = .0005). Median PFS was NR with atezolizumab vs 6.9 months with placebo.
* Biomarker analysis: Whole Exome Sequencing (WES) was performed on 234 samples (88% of available dMMR samples, and a portion of non-dMMR samples).