Final results of the RAPP-01 phase III trial comparing doxorubicin and docetaxel with doxorubicin and cyclophosphamide in the adjuvant treatment of high-risk node negative and limited node positive (≤3) breast cancer patients.

Abstract

Abstract Abstract #4101 Background
 Taxanes have been approved in the adjuvant setting for the treatment of node positive (pN+) breast cancer (BC) patients (pts), given either sequentially or in combination with anthracyclines. Controversies remain regarding their role in high-risk node negative (pN0) disease.
 Methods
 In 1999, we initiated a randomised phase III trial comparing 4 cycles of adjuvant doxorubicin + docetaxel (AT, 50/75/mg/m²) with 4 cycles of standard doxorubicin + cyclophosphamide (AC, 60/600/mg/m²) in a mixed population of high-risk pN0 and limited pN+ (≤3) early BC pts. Chemotherapy was delivered postoperatively q3w without prophylactic G-CSF, followed by radiation therapy according to standard guidelines and endocrine treatment for 5 years in pts with ER±PgR-positive tumours. This trial was closed prematurely for toxicity in 2003 and we have reported the safety data (JAMA 293:2367, 2005). We now report on time to recurrence (TTR, primary endpoint defined as locoregional relapse, controlateral BC or distant metastasis, which ever occurs first) as well as the effect of treatment by stratification factors [pN and Ki67 (<25% vs ≥25%)].
 Results
 Of 700 pts planned, 627 were enrolled between 6/1999 and 1/2003. Baseline characteristics of all pts were well-matched, with 43% of pN0 and 44% of Ki67 ≥25%. At a median follow-up of 64 months, there was no statistically significant difference in TTR between AT and AC. In the AT group, there were 28 TTR events (5-year TTR 91%, 95%CI: [88-94%]) and 16 deaths all causes (2 toxic deaths); the AC group had 31 TTR events (5-year TTR 90.9%, 95%CI: [88-94%]) and 18 deaths all causes.
 
 Conclusions
 With 5-year median follow-up, there is no difference in TTR between pts treated with AT or standard AC in adjuvant setting. Specific nodal or Ki67 status do not confer any additional benefit from either regimen. Both regimen provide an excellent 5-year TTR rate (>90%). Multivariate analysis including all prognostic covariates will be performed and presented at the meeting. Given the high risk of life-threatening complications already reported, AT is not manageable without preventive strategies (e.g. G-CSF) and cannot be considered as a standard combination for intermediate risk early BC. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4101.