Trastuzumab duration effects within patient prognostic subgroups in the PHARE trial.
BACKGROUND
At 42.5 months of median follow-up, PHARE failed to show that 6 was non-inferior to 12 months 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 the multivariate Cox proportional hazards regression models were carried out on metastases-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-month 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 metastatic events were observed and four prognostic groups were defined: very low, low, intermediate and high risk in the 12-month arm. The corresponding 3-year MFS rates were 98.3%, 95.8%, 90.4% and 78.4% in the four prognostic groups, respectively. In the 6-month arm, the 3-year MFS rates were 98.3%, 94.2%, 85.7% and 74.8% in the four prognostic groups, respectively.


CONCLUSIONS
In the very low-risk group, 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.
Methdology and Biostatistics Unit, Centre Oscar Lambret, Lille.
A
A
Kramar
Department of Medical Oncology, Centre Léon Bérard, Lyon.
T
T
Bachelot
Department of Medical Oncology, Institut Bergonié, Bordeaux.
N
N
Madrange
Department of Medical Oncology, Institut Curie, Paris.
J-Y
JY
Pierga
Department of Medical Oncology, Centre Eugene Marquis, Rennes.
P
P
Kerbrat
Department of Medical Oncology, University Hospital Saint-Louis, Paris.
M
M
Espié
Department of Medical Oncology, Centre Georges François Leclerc, Dijon.
P
P
Fumoleau
French National Cancer Institut, Boulogne-Billancourt.
I
I
Pauporté
Department of Medical Oncology, University Hospital Pitié Salpetrière, Paris.
D
D
Khayat
Department of Medical Oncology, Val d'Aurelle Institut Régional du Cancer, Montpellier.
G
G
Romieu
Department of Medical Oncology, University Hospital Besancon, Besancon, France xavier.pivot@univ-fcomte.fr.
X
X
Pivot
D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D005260:Female; D005602:France / Q000453:epidemiology; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D016019:Survival Analysis; D000068878:Trastuzumab; D047368:Tumor Burden
D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
adjuvant treatment; breast cancer; prognosis; trastuzumab