Superiority of sequential docetaxel over standard FE100C in patients with intermediate risk breast cancer: survival results of the randomized intergroup phase III trial EC-Doc.

Abstract

Abstract Abstract #78 Background: Taxane based adjuvant chemotherapy (CHT) is standard of care in node-positive breast cancer. Several pre-planned subgroup analyses detected the maximum benefit from taxanes in patients with 1-3 positive lymph nodes (LN).
 According to the St. Gallen consensus CHT in endocrine responsive tumors is optional in these patients. Recently the ABCSG reported excellent survival data after endocrine therapy +/- bisphosphonates without CHT in low to intermediate risk breast cancer (Gnant et al., ASCO 2008). The EC-Doc trial compares a modern sequential taxane-based regimen with standard FE100C in patients with 1-3 positive LN.
 Methods: Patients from 18 to 65 years with primary breast cancer and 1 to 3 positive LN were eligible if they had operable breast cancer with histologically confirmed free margins. M0 status was assessed by conventional staging. 2011 patients were randomized to a phase III trial comparing 4 cycles E90C600 q3w followed by 4 cycles of Docetaxel100 q3w (n=1008) (Arm A) versus 6 cycles of F500E100C500 q3w (n=828) or C600M40F600 d1, 8 q4w (n=175) (Arm B). The primary endpoint is EFS. Secondary endpoints are OS, toxicity and quality of life.
 Results: Baseline characteristics were well balanced between both study arms. Arm A/B: mean age 51.5/51.5 years, median tumor size 2.0/2.0, HR positive 77.7% / 78.3%, G3 34.1% / 34.4%. Toxicity data from the EC-Doc trial were recently presented (Nitz et al. , ASCO 2008). After a median follow up of 41 months both estimated 5-year EFS (91% vs. 86%, p=0.005) and OS (95% vs. 90%, p=0.004) were significantly better in the EC-Doc arm.
 For the comparison of EC-Doc vs. FE100C the respective values were: HR 0.58, p=0.004, estimated 5 year EFS 91% / 85% and 5 year estimated OS 95% / 91% (p =0.03). For the hormone receptor positive subpopulation the HR was 0.51 in favour of EC-Doc (p= 0.007).
 Conclusions: Our study indicates a superiority of sequential taxane-based EC-Doc CHT in terms of EFS and OS over standard FE100C in an intermediate risk group. The addition of modern third generation taxane based CHT to conventional endocrine treatment is associated with excellent EFS and OS in patients with 1-3 positive LN.
 As shown even for the subgroup of patients with HR positive disease the benefit from third generation taxane based CHT is substantial so that an endocrine only adjuvant strategy may result in undertreatment. With respect to the excellent survival rates prospective randomized trials testing the existing genetic tests are mandatory.
 Updated survival and efficacy analysis in distinct molecular subtypes (Her-2/neu, triple-negative) will be presented. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 78.