2553 - 9 weeks versus 1 year adjuvant trastuzumab for HER2+ early breast cancer: subgroup analysis of the ShortHER trial allows to identify patients for whom a shorter trastuzumab administration may have a favourable risk/benefit ratio

Background

In the ShortHER trial, 1254 HER2+ early breast cancer patients were randomized to 9 weeks versus 1 year trastuzumab. At 6 years median follow up, non inferiority could not be claimed according to the frequentistic approach (HR 1.13; 90% CI 0.89;1.42) with the upper limit of CI crossing the non inferiority margin set at 1.29. However, based on the pre-planned Bayesian analysis, the probability that the short arm is not inferior to the long one was 80%. Moreover, G >/= 2 cardiac events were 82 in the long and 27 in the short arm (RR 0.33, 95% CI 0.22 to 0.55). It is therefore of interest to identify subgroups of patients for whom, based on the risk/benefit ratio, a shorter treatment might be an option

Methods

At multivariate analysis, pathologic tumor size and nodal status were independent prognostic parameter for Disease-Free Survival (DFS) and three prognostic groups could be identified: low risk (pT 2cm and N 0-3) and high risk (pT > 2cm and N 4+).

Results

The low, intermediate and high risk groups included 37.5%, 51.9% and 10.5% of the patient population, respectively. The 5 year DFS and G>/=2 cardiac events in the long and short arms according to the prognostic group are summarized below:

Conclusions

Subgroups analysis of the ShortHER trial allows to identify patients at low and intermediate risk of relapse. This population includes 89% of the patients and the 5 year DFS is not different in the two treatment arms (89% long, 88% short; HR 1.02, 95% CI 0.78-1.33); on the contrary, the risk of cardiac events is significantly higher in the long arm (12.8% vs 4.5%; RR 2.88, 95% CI 1.85-4.47). These results may contribute to better define the risk/benefit ratio of 1 year adjuvant trastuzumab.

Clinical trial identification

EUDRACT number: 2007-004326-25

NCI ClinicalTrials.gov number: NCT00629278

Editorial Acknowledgement