Molecular subtype stratified response to adjuvant therapy in endometrial cancer (086)

Abstract

Objectives: Molecular classification of endometrial cancer (EC) has been shown to have a strong prognostic value. Recent data support the predictive implications of molecular subtype assignment. Using combined EC cohorts that have undergone molecular classification, our objective was to assess the response to adjuvant therapy based on ESMO 2016 risk group criteria within the four molecular subtypes (MMRd, POLEmut, NSMP, and p53abn). Methods: Historical institutional (29%) and population-based cohorts of EC from 2016 (53%) and prior to 2016 (18%) that had undergone molecular classification were identified. We assessed outcomes (overall, disease-specific, or progression-free survival [OS, DSS, PFS]) based on the adjuvant treatment given, including none, vault brachytherapy (VB) only, external beam radiation (EBRT) ± VB, or chemotherapy (± any RT including EBRT or VB) across ESMO risk groups (low, intermediate, high-intermediate, high and advanced/metastatic) within the four molecular subtypes. Conclusions: Although retrospective data regarding where the treatment was given was not confined to clinical trial parameters and need to be interpreted with caution, these results are consistent with the PORTEC3 trial subgroup analysis showing chemotherapy does not appear to add benefit within MMRd EC but may improve outcomes for patients with p53abn EC. These findings support molecular subtype-directed trials, such as radiation alone ± investigational agent for MMRd, chemotherapy ± investigational agent for p53abn, and de-escalation of adjuvant therapy for POLEmut EC. Objectives: Molecular classification of endometrial cancer (EC) has been shown to have a strong prognostic value. Recent data support the predictive implications of molecular subtype assignment. Using combined EC cohorts that have undergone molecular classification, our objective was to assess the response to adjuvant therapy based on ESMO 2016 risk group criteria within the four molecular subtypes (MMRd, POLEmut, NSMP, and p53abn). Methods: Historical institutional (29%) and population-based cohorts of EC from 2016 (53%) and prior to 2016 (18%) that had undergone molecular classification were identified. We assessed outcomes (overall, disease-specific, or progression-free survival [OS, DSS, PFS]) based on the adjuvant treatment given, including none, vault brachytherapy (VB) only, external beam radiation (EBRT) ± VB, or chemotherapy (± any RT including EBRT or VB) across ESMO risk groups (low, intermediate, high-intermediate, high and advanced/metastatic) within the four molecular subtypes. Conclusions: Although retrospective data regarding where the treatment was given was not confined to clinical trial parameters and need to be interpreted with caution, these results are consistent with the PORTEC3 trial subgroup analysis showing chemotherapy does not appear to add benefit within MMRd EC but may improve outcomes for patients with p53abn EC. These findings support molecular subtype-directed trials, such as radiation alone ± investigational agent for MMRd, chemotherapy ± investigational agent for p53abn, and de-escalation of adjuvant therapy for POLEmut EC.