LBA11 - Prognostic impact of Recurrence Score (RS), grade/Ki67 central pathological review, and anthracycline (A)-free vs. A-containing chemotherapy (CT)...

Date 09 September 2017
Event ESMO 2017 Congress
Session Breast cancer, early stage
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Early Stage
Breast Cancer
Pathology/Molecular Biology
Presenter Oleg Gluz
Citation Annals of Oncology (2017) 28 (suppl_5): v605-v649. 10.1093/annonc/mdx440
Authors O. Gluz1, U. Nitz1, M. Christgen2, W. Malter3, M. Clemens4, T. Reimer5, B. Nuding6, B. Aktas7, A. Stefek8, A. Ppllmanns9, F. Lorenz-Salehi10, C. Uleer11, P. Krabisch12, S. Kümmel13, C. Liedtke14, S. Shak15, R. Kates16, R. Wurstlein17, H.H. Kreipe2, N. Harbeck18
  • 1Breast Center Niederrhein, West German Study Group and Bethesda Clinics Mönchengladbach, 41061 - Mönchengladbach/DE
  • 2Pathology, Medical School Hannover, Hannover/DE
  • 3Department Of Gynecology And Obstetrics, University Clinics Cologne, Cologne/DE
  • 4Oncology, Klinikum Mutterhaus der Borromäerinnen, 54290 - Trier/DE
  • 5Gynecology, University Clinics Rostock, Rostock/DE
  • 6Gynecology, Evangelisches Krankenhaus Bergisch Gladbach, 51465 - Bergisch Gladbach/DE
  • 7Gynecology And Obstetrics, University Clinics Essen, Essen/DE
  • 8Breast Center, Johanniter Clinics Stendal, Stendal/DE
  • 9Gynecology And Obstetrics, Evangelical Hospital Oberhausen, Oberhausen/DE
  • 10Gynecology, HSK Wiesbaden, Wiesbaden/DE
  • 11--, Gynecological-oncology practice, Hildesheim/DE
  • 12Gynecology And Obstetrics, City Hospital, Chemnitz/DE
  • 13Breast Center, Kliniken Essen Mitte Evang. Huyssens-Stiftung, 45136 - Essen/DE
  • 14Gynecology And Obstetrics, University SH.-Lübeck, 23538 - Lübeck/DE
  • 15--, Genomic Health Inc, 94063 - Redwood City/US
  • 16--, West German Study Group and Bethesda Clinics Mönchengladbach, 41061 - Mönchengladbach/DE
  • 17Breast Center, Ludwig Maximilians University - Grosshadern, 81377 - Munich/DE
  • 18Breast Center, University of Munich (LMU), Munich/DE

Abstract

Background

Optimal prognostic markers and survival impact of A-containing CT in HER2-, particularly HR+ EBC, are still a matter of debate.

Methods

WSG PlanB is the first prospective trial compared A-free 6xTC vs. standard 4xECà4xDoc in high-risk pN0 or pN+ HER2- EBC and RS > 11 in pN0-1 HR+/HER2- EBC. Primary endpoint was DFS. Secondary endpoints included DDFS/LRFS and overall survival (OS). Multivariable analysis included continuous RS, IHC4, ER, PR, Ki67 (centrally measured), local/central grade, age, nodal status, tumor size, treatment, surgery type.

Results

From 2009 to 2011, PlanB enrolled 3198 pts. 2449 pts. were randomized. to 6xTC vs. 4xEC→4xDoc (n = 1222/1227). After 60 months median follow-up, similar 5y DFS of 90%, 5y DDFS of 94%/93% (TC/EC-Doc) and 5y OS of 95% were observed in both arms. Pts with RS 0-11 without CT (n = 348, 15.3%) had 5-year DFS of 94%, irrespective of nodal status. 5y DDFS was 97.8% in RS 0-11 pts (all and only ET-treated: pN0: 97.7%, pN1: 97.9%), 96.9% in RS12-25 and 89.7% in RS > 25 (p  25 vs. either RS 0-11 or RS 12-25). RS was the strongest independent predictor for DDFS (HR = 2.64; 95% CI: 1.67-4.17) in multivariable analysis (all and CT-treated); the model also included tumor size>2 cm, nodal status, local grade 3. 5y LRFS was 98.6% in RS 0-11, 99.3% in RS 12-25 and 98.0% in RS > 25 (p = 0.002 for RS > 25 vs. RS 12-25, p = 0.21 for RS > 25 vs. RS 0-11). In multivariable analysis Ki67 (HR = 3.62, 95% CI: 1.39-9.47), together with >pN2 and mastectomy (all and CT-treated) predicted LRFS.

Conclusions

We observed excellent 5y DDFS of 97.8% in clinically high/genomic low risk HER2- HR+ EBC pts treated by ET alone. TC and EC-Doc resulted in similar outcomes. High RS was predictive for poor DDFS and LRFS by univariable, and for DDFS by multivariable analysis; Ki67 was independently prognostic for LRFS. These first prospective data regarding the impact of RS on DDFS and LRFS in clinically intermediate/high-risk EBC underline the importance of using both clinicopathological and genomic markers for individualized therapy decisions.

Clinical trial identification

EUDRA-CT Number: 2008-004263-19

Legal entity responsible for the study

West German Study Group

Funding

Amgen; Sanofi-Aventis; Genomic Health

Disclosure

O. Gluz: Honoraria and/or travel support (GHI, Nanostring, Amgen, Roche). U. Nitz, S. Kümmel, C. Liedtke, S. Shak, H.H. Kreipe: Genomic Health. R. Wurstlein, N. Harbeck: Genomic Health, Agendia, Nanostring. All other authors have declared no conflicts of interest.