2017 ASCO Annual Meeting!
Session: Breast Cancer—Local/Regional/Adjuvant
Type: Oral Abstract Session
Time: Monday June 5, 9:45 AM to 12:45 PM
Location: Hall D2
Prospective WSG phase III PlanB trial: Final analysis of adjuvant 4xEC→4x doc vs. 6x docetaxel/cyclophosphamide in patients with high clinical risk and intermediate-to-high genomic risk HER2-negative, early breast cancer.
2017 ASCO Annual Meeting
J Clin Oncol 35, 2017 (suppl; abstr 504)
Author(s): Nadia Harbeck, Oleg Gluz, Michael R. Clemens, Wolfram Malter, Toralf Reimer, Benno Nuding, Bahriye Aktas, Andrea Stefek, Anke Pollmanns, Fatemeh Lorenz-Salehi, Christoph Uleer, Petra Krabisch, Sherko Kummel, Cornelia Liedtke, Steven Shak, Rachel Wuerstlein, Matthias Christgen, Ronald Kates, Hans Heinrich Kreipe, Ulrike Nitz, West German Study Group; Brustzentrum der Universität München (LMU), Munich, Germany; West German Study Group, Moenchengladbach, Germany; Department of Hematology and Oncology, Mutterhaus der Borromaeerinnen, Trier, Germany; Department of Obstetrics and Gynecology, University Hospital of Cologne, Cologne, Germany; Department of Obstetrics and Gynecology, University of Rostock, Rostock, Germany; Department of Obstetrics and Gynecology, Protestant Hospital Bergisch Gladbach, Bergisch Gladbach, Germany; University Hospital Essen, Essen, Germany; Johanniter Krankenhaus, Genthin-Stendal, Germany; EKO, Oberhausen, Germany; HSK Wiesbaden, Wiesbaden, Germany; Gynecology Practice, Hildesheim, Germany; Department of Gynecology and Obstetrics, Klinikum Chemnitz, Chemnitz, Germany; Breast Unit, Kliniken Essen-Mitte, Essen, Germany; University of Schleswig-Holstein Campus Luebeck, Lübeck, Germany; Genomic Health, Redwood City, CA; LMU Munich, Munich, Germany; Hannover Medical School, Hannover, Germany; West German Study Group, Evangelic Hospital Bethesda, Moenchengladbach, Germany
Background: Optimal chemotherapy in HER2-negative, particularly HR-positive, early breast cancer (EBC), especially the survival impact of anthracyclines, is still a matter of debate. Retrospective analyses saw most benefit of 6xCEF vs. 6xCMF in HER2+ EBC. Prospective trials have shown conflicting results; no predictive molecular factors have been validated so far, particularly for HR+ EBC. The WSG PlanB trial is the first trial that randomized only patients with high clinical risk or with Recurrence Score >11 in the HR+/HER2- subgroup (pN0-1). Patients with RS<11 (pN0-1) had an excellent prognosis (five-year DFS of 94%) with endocrine therapy alone (Gluz et al. ASCO 2016). Methods: The WSG PlanB trial was originally planned as a non-inferiority study for comparison of 6 cycles of anthracycline-free TC (Arm A) vs. standard anthracycline-taxane based chemotherapy (4xEC→4xDoc) (Arm B) in patients with high-risk pN0 (T2-4, G2-3, <35 years, or high uPA/PAI-1) or pN+ HER2- EBC. Following an early amendment, Oncotype DX was performed in all HR+ tumors, and omission of chemotherapy (CT) was recommended in RS≤11 HR+ pN0-1 disease. Primary endpoint was DFS, defined as time to any recurrence, secondary cancer or death. Final analysis for the CT randomization was planned after completed 5-year follow-up in all patients. Results: From 2009 to 2011, PlanB enrolled 3198 patients (n=3073 with central pathology review). In 348 patients (15.3%), CT was omitted based on RS≤11. 2449 patients were randomized to 6xTC (n=1222) and 4xEC→4xDoc (n=1227). Within this cohort, 41% were pN+, 42% had G3 tumors and 18% HR-negative tumors by central pathology. After median follow-up of 61 months, very similar five-year DFS of 89.9% [88.1%-91.7%] vs. 90.2% [88.4%-92.0%] and five-year OS of 94.7% [93.4%-96.1%] vs. 94.6% [93.2%-96.0%] were observed in Arms A vs. B. Five treatment-related deaths were observed in Arm A (TC) vs. one in Arm B (EC-Doc) (0.4% vs. 0.1%), despite a trend to more SAE’s in Arm B vs. Arm A (n=397 vs. 358). Although recurrence score is a strong prognostic factor, it was not predictive for anthracycline efficacy; no efficacy differences between the study arms were observed in (locally) triple-negative patients or in those with >4 involved lymph nodes, despite the prognostic impact of these factors. Conclusion: In the WSG PlanB trial, patients with early HER2-negative BC seem to be sufficiently treated by six cycles of docetaxel/cyclophosphamide compared to four cycles of EC followed by four cycles of docetaxel -- no efficacy differences are evident in high-risk subgroups defined by triple-negative status, nodal status, or high Recurrence Score. Further prospective studies are urgently needed before final conclusions for impact of anthracyclines in HER2-negative BC can be drawn. Clinical trial information: NCT01049425