WSG PLAN B trial: Evaluating efficacy of anthracycline-free chemotherapy in primary HER2-negative breast cancer after molecular-based risk assessment according to Oncotype DX and uPA/PAI-1.
Authors: O. Gluz, C. Liedtke, S. Markmann, S. Henschen, M. R. Clemens, M. Salem, C. Thomssen, H. Kreipe, N. Harbeck, U. Nitz
Journal: Journal of Clinical Oncology (2010)

TPS106^ Background: Anthracycline- and taxane-based adjuvant chemotherapy (CHT) is standard of care in N+ breast cancer (BC) and shown to be the most effective regimen in N- BC, but overtreatment remains a major problem in both groups. Although a retrospective meta-analysis suggested highest benefit of anthracyclines (vs. CMF) in HER2+ BC, patient groups with HER2- BC deriving anthracycline benefit still need to be defined prospectively. Modern gene signatures identify a substantial number of patients at low risk of recurrence currently misclassified by conventional prognostic factors. The WSG Plan B trial compares an anthracycline-containing CHT regimen (ECx4-Docx4), with an anthracycline-free taxane-based regimen (TCx6) in patients with HER2- BC. In order to assess whether molecular-based risk assessment may prevent overtreatment, Plan B incorporates the 21-Gene Recurrence Score (RS) as mandatory risk stratification in hormone-receptor (HR)+ patients with 0-3 involved lymph nodes. Recent data suggest that patients with low RS do not derive significant benefit from adjuvant CHT regardless of nodal status. Methods: Patients aged 18 to 75 years with high-risk primary BC are eligible. High-risk criteria comprise N+ or tumor size >2 cm, grade 2-3, age <35 years, high uPA/PAI-1 or HR- in N0 patients. A total of 2,448 patients are planned to be randomized to receive either 4 × epirubicin90/cyclophosphamide600 q3w followed by 4 × docetaxel100 q3w or 6 × Docetaxel75cyclophosphamide600 q3w. Importantly, patients with 0-3 positive lymph nodes and low RS (<11) will be spared CHT but receive endocrine therapy alone. Central pathology and evaluation of histology, grade, expression of KI-67, HR, HER2 and 2T Score (Topo-IIa/TIMP-1) will be performed prospectively. Furthermore, blood samples for pharmacogenomic and circulating tumor cells analyses will be obtained prior to randomization. The primary study endpoint is event-free survival. Secondary endpoints comprise overall survival, toxicity, quality of life, and economical endpoints as well as translational research. Between 03/2009 and 01/2010, 730 patients have been registered. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Genomic Health, sanofi-aventis Amgen, Genomic Health, sanofi-aventis In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519-521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2010 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest.