IHC Can Select Best Endometrial Cancer Candidates for Bevacizumab Plus Chemotherapy

Phase 2 trial results show that a certain high-risk endometrial cancer can be identified by determining p53 status via immunohistochemistry (IHC). Bevacizumab plus chemotherapy significantly improves progression free survival (PFS) and overall survival (OS) in this specific, high-risk tumor genotype/phenotype. The study authors wrote, “Clinical management of advanced endometrial cancer is transitioning from histologic subtype to molecular stratification. The most aggressive molecular subtype is abnormal p53; however, a major debate is how to appropriately determine p53 status.”

Using data from the randomized phase 2 GOG-86P trial, an analysis was done to integrate p53 status as determined by IHC with the presence or absence of a TP53 mutation in 213 tumors treated either with chemotherapy plus bevacizumab or chemotherapy plus temisirolimus. Data was then analyzed for primary outcomes of PFS and OS in both treatment arms.

Chemotherapy plus bevacizumab in patients with overexpressed p53 yielded a PFS hazard ratio (HR) of 0.46 (95% confidence interval [CI], 0.26 to 0.88) and an OS HR of 0.31 (95% CI, 0.16 to 0.62). Patients in the chemotherapy plus bevacizumab arm with overexpressed p53 and TP53 mutation experienced a PFS HR of 0.41, (95% CI, 0.22 to 0.83) and an OS HR of 0.28 (95% CI, 0.14 to 0.59). There was an 88% concordance reported between TP53 next generation sequencing (NGS) and p53 IHC.

The study authors concluded, “IHC for p53 alone or when integrated with sequencing for TP53 identifies a specific, high-risk tumor genotype/phenotype for which bevacizumab is particularly beneficial in improving outcomes when combined with chemotherapy,” explained Dr Thiel et al. “Determining p53 status by IHC is a fast, cost-effective, and reliable method that can be easily integrated into clinical management of advanced endometrial cancer.”

Source:

Thiel KW, Devor EJ, Filiaci VL, et al. TP53 Sequencing and p53 Immunohistochemistry Predict Outcomes When Bevacizumab Is Added to Frontline Chemotherapy in Endometrial Cancer: An NRG Oncology/Gynecologic Oncology Group Study [published online ahead of print, 2022 Jun 3]. J Clin Oncol. 2022;JCO2102506. doi:10.1200/JCO.21.02506