Trastuzumab duration effects within patient prognostic subgroups in the PHARE trial
A partir de données de l'essai PHARE portant sur 3 380 patientes atteintes d'un cancer du sein HER2+ de stade précoce (durée médiane de suivi : 42,5 mois), cette étude française évalue, du point de vue de la survie sans métastases, les effets de la durée d'un an de traitement adjuvant à l'aide de trastuzumab selon quatre sous-groupes définis par le niveau du risque de récidive
Background : At 42.5 months of median follow-up PHARE failed to show that 6 was non-inferior to 12 month of adjuvant trastuzumab. From the results of PHARE questions remain regarding whether the magnitude of benefit derived from 1 year is sufficient to justify its systematic use for different patient subgroups. Methods : Treatment effects were evaluated according to various tumour characteristics, and multivariate Cox proportional hazards regression models were performed on metastases disease free survival (MFS) in the 12 months control arm. A prognostic score was defined providing the identification of patient categories with similar risks. The 6 months arm was used as a validation set in order to test for heterogeneity. This study is registered at clinicaltrials.gov, number NCT00381901. Results : A total of 261 M-DFS metastatic events were observed and 4 prognostic groups were defined: very low, low, intermediate and high risk in the 12 months arm. The corresponding 3-year MFS rates were 98.3%, 95.8%, 90.4% and 78.4% in the 4 prognostic groups, respectively. In the 6 months arm, the 3-year MFS rates were 98.3%, 94.2%, 85.7%, and 74.8% in the 4 prognostic groups, respectively. Conclusion : In the very low risk groups, the potential absolute benefit of standard duration of trastuzumab was small enough to indicate that optimal standard treatment might be clinically questionable. On the other hand, the 3-year metastasis occurrence rates strongly support the need for a search of a more efficient treatment in the low, intermediate and high risk groups.
Annals of Oncology 2014