The addition of paclitaxel to doxorubicin and cisplatin and volume-directed radiation does not improve overall survival (OS) or long-term recurrence-free survival (RFS) in advanced endometrial cancer (EC): A randomized phase III NRG/Gynecologic Oncology Group (GOG) study

Objectives. To determine if the addition of paclitaxel (P) to cisplatin and doxorubicin (CD) following surgical debulking and volume-directed radiation therapy improved long-term, recurrence-free survival (RFS) and overall survival (OS) in patients with advanced-stage endometrial cancer (EC). Methods. Prospective, randomized GOG trial comparing (CD) (50 mg/m(2))/(45 mg/m(2)) +/ (P) (160 mg/m(2)) following volume-directed radiation and surgery in advanced EC. A Kaplan-Meier (KM) analysis characterized the relationship between treatment arms and the OS outcome, a log-rank test assessed the independence of treatment with the OS outcome, and the treatment effect on estimated OS was determined using a Cox proportional hazards (PH) model stratified by stage. The PH assumption was assessed using a test of interaction between treatment variable and the natural logarithm of survival time. Adverse events, regardless of attribution, were graded. Results. Since initial publication, 60 deaths occurred, leaving 311 patients alive with 290 (93.8%) recurrence free. There was no significant decrease in the risk of recurrence or death associated with the CDP treatment regimen stratified for stage (p = 0.14, one-tail). The exploratory analysis for OS and the corresponding homogeneity tests for different effects across subgroups revealed only EFRT and EFRT & GRD status to have significantly different treatment effects (p = 0.027 and p = 0.017, respectively). Second primary malignancies were identified in 17/253 (6.4%) and 19/263 (7.0%) of patients treated with CD and CDP respectively. Breast (2.4%) followed by colon (1%) were the two cancers most frequently diagnosed in this setting. Conclusion. No significant difference between treatment arms was identified. Subgroup analysis both in the initial and current reports demonstrated a trend towards improved RFS and OS in patients treated with CDP and EFRT. This long-term analysis of outcomes also identified the necessity of providing on-going cancer screening to patients enrolled in trials. (C) 2019 Published by Elsevier Inc.