Five year Analysis of the FNCLCC-PACS04 Trial: FEC 100 vs ED75 for Adjuvant Treatment of Node-Positive Breast Cancer

32th annual SABCS (San Antonio Breast Cancer Symposium) - San Antonio, 9-13 décembre 2009

Henri Roché, Djelila Allouache, Gilles Romieu, Hugues Bourgeois, Jean-Luc Canon, Daniel Serin, Patrice Viens, Louis Mauriac, Alain Monnier, Anita Vindevoghel, Nadine Dohollou, Elisabeth Luporsi, Jean-Marc Ferrero, Bruno Audhuy, Catherine Dopchie, Laurent Cany, Etienne Brain, Marta Jimenez, Lise Roca and Marc Spielmann for the FNCLCC Breast Group


To evaluate the combined administration of Docetaxel (D) and Epirubicin (E) versus FEC 100 on 5-year disease-free survival
(DFS) among non metastatic lymph node-positive breast cancer patients (pts).

Patients and Methods

Main inclusion criteria were: localized unilateral breast cancer, age < 65 years, at least one positive node, no metastasis,
normal cardiac, hepatic, haematological and renal functions. Pts were randomized to receive on day 1 every 3 weeks either
Arm A: 6 cycles of FEC100 (F and C, each at 500 mg/m², E 100 mg/m²); or Arm B, 6 cycles of ED (E and D, each at 75 mg/
m²). G-CSF was mandatory for all subsequent cycles after either febrile neutropenia or treatment delay for neutropenia.
Radiotherapy was given after conservative surgery. Hormone therapy was prescribed to pts with positive hormone receptors
(HRs). Pts overexpressing HER2 were secondly randomized to sequential one year of trastuzumab or observation. Sample
size calculation was based on an expected 10% absolute difference in 3–year DFS for HER2+ pts. Assuming a 20% prevalence
of HER2 positivity, a total of 3,000 pts were to be randomised, allowing to detect an absolute difference of 6% in 5-year DFS
in favour of one of the two chemotherapy regimens.


Between February 2001 and August 2004, 3,010 pts were randomized in France and Belgium. Pts characteristics were well
balanced between the 2 arms: median age 50 years, post-menopausal status 48%, breast-conserving surgery 70%, tumor
size >2cm 49%, SBR grade III 40%, both HRs negative 20%, both HRs positive 62%, 1-3 involved nodes 67%, HER2+
19%. Treatment was completed for 96% of pts in both arms. Febrile neutropenia was reported for 2.0% and 6.4% of cycles
respectively in Arms A and B. Grade 3-4 NCI-CTC neutropenia were reported for 34% and 9% of pts on day 21(Arms A and
B). Other grade 3-4 toxicities were: leucopenia (35 vs 47%), thrombopenia (1.7 vs 0.3%), nausea/vomiting (14 vs 8%) and
mucositis (3.2 vs 3.3%). No toxic death was reported.As of April 2009, the median follow-up was 59.3 months. Overall, 576
pts experienced at least one event: 103 loco-regional relapses, 398 metastasis, 46 contralateral breast cancer, and 29 deaths
as fi rst event. A total number of 35 second cancers and 288 deaths are registered. The 5-year DFS rates were 79.7% (95%CI:
77.4-81.7) and 81.7% (95%CI: 79.6-83.7) in arms A and B respectively (HR=0.89, 95%CI: 0.76-1.05, p=0.18). Multivariate
Cox regression analysis, adjusted for age, tumor size, SBR grade, HRs and stratifi ed for lymph node status, revealed a
signifi cant interaction term between treatment and HER2 (p=0.01).Five-year overall survival rates (OS) were 90.3% (95%CI:
88.5-91.8) with FEC and 90.1% (95%CI: 88.3-91.6) with ED (HR=1.07, 95%CI: 0.85-1.35, p=0.54).


No advantage in DFS or OS was observed by combination of D to E when compared to standard FEC100. The best use of
D in the adjuvant setting is still uncertain.

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