• Reproductive Cancers
• Oncology Clinical Trials
• Adjuvant/Neoadjuvant Therapy

• Reproductive Cancers
• Oncology Clinical Trials
• Oncology
• Adjuvant/Neoadjuvant Therapy

Patients with stage I or II endometrial cancer are generally treated with surgery. Despite radical surgery, however, patients with medium- or high-risk stage I and II endometrial cancers are still at significant risk of local and distant progression. Adjuvant radiotherapy has not been shown to improve survival, and adjuvant chemotherapy alone has shown greater survival benefit in patients with more advanced disease [Creutzberg CL et al. Curr Oncol Rep. 2011]. The current phase 3 study [NCT01244789] is preparing to evaluate whether survival can be improved in intermediate- and high-risk early-stage patients by offering postoperative chemotherapy instead of postoperative observation alone (standard strategy).

Frederic Amant, MD, EORTC and University of Leuven, Leuven, Belgium, presented the design of the study, which will evaluate this premise in patients with medium- or high-risk node-negative stage I or II endometrial cancer. Eligible patients must have a diagnosis of stage I grade 3, stage II, or stage I or II type 2 endometrioid adenocarcinoma and have undergone hysterectomy and bilateral salpingo- oophorectomy and pelvic lymphadenectomy (LNE; minimum, 12 pelvic nodes; para-aortic LNE optional). All patients are required to be World Health Organization performance status 0 to 2.

Eligible patients will be stratified by histology (endometrioid vs nonendometrioid), stage (1a vs 1b vs 2 disease), para-aortic (≥ 10) and pelvic (≥ 20) LNE versus lesser LNE, and brachytherapy (planned yes/no); they will then be randomized (1:1) to postoperative adjuvant paclitaxel (175 mg/m²) and carboplatin (AUC5) every 3 weeks for a total of 6 courses or postoperative follow-up without any further treatment. Adjuvant brachytherapy is permitted in both arms; external beam radiotherapy is not allowed. All patients will be followed for a minimum of 3 years.

The primary study end point is overall survival. Secondary end points include disease-specific survival, progression-free survival, toxicity, quality of life based on patient-reported outcomes (EORTC QLQ-C30 and QLQ-EN24—quality-of-life questionnaires for cancer and endometrial cancer), as well as the rates of isolated pelvic relapse (central and/or pelvic wall), isolated distant relapse, and mix of local and distant relapse. This trial is powered to detect a survival difference of 12%, from 74% to 86% in the endometrioid subgroup for the preplanned subgroup analyses; all other subgroup analyses are exploratory.

Additional translational research objectives include an evaluation of the prognostic and predictive values of tumor biomarkers for clinical outcome, stage, grade of disease, and presence of certain toxicities to chemotherapy. Objectives also include assessment of protein expression and prognostic or predictive markers (eg, EGFR, KRAS, BRAF, NRAS, PIK3CA, PTEN, TP53, and FBXW7) for use in characterizing patients for potential future individual treatment strategies.

This international trial is now enrolling new sites. As of the date of presentation, 44 patients had been randomized to treatment, with a total expected enrollment of 678 patients.

• © 2014 MD Conference Express®