A Kramar1, T Bachelot2, N Madrange3, J-Y Pierga4, P Kerbrat5, M Espié6, P Fumoleau7, I Pauporté8, D Khayat9, G Romieu10, X Pivot11. 1. Methdology and Biostatistics Unit, Centre Oscar Lambret, Lille. 2. Department of Medical Oncology, Centre Léon Bérard, Lyon. 3. Department of Medical Oncology, Institut Bergonié, Bordeaux. 4. Department of Medical Oncology, Institut Curie, Paris. 5. Department of Medical Oncology, Centre Eugene Marquis, Rennes. 6. Department of Medical Oncology, University Hospital Saint-Louis, Paris. 7. Department of Medical Oncology, Centre Georges François Leclerc, Dijon. 8. French National Cancer Institut, Boulogne-Billancourt. 9. Department of Medical Oncology, University Hospital Pitié Salpetrière, Paris. 10. Department of Medical Oncology, Val d'Aurelle Institut Régional du Cancer, Montpellier. 11. Department of Medical Oncology, University Hospital Besancon, Besancon, France xavier.pivot@univ-fcomte.fr.
Abstract
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. CONCLUSION: 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.
RCT Entities:
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. CONCLUSION: 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.
Authors: Hadar Goldvaser; Yasmin Korzets; Daniel Shepshelovich; Rinat Yerushalmi; Michal Sarfaty; Domen Ribnikar; Paaladinesh Thavendiranathan; Eitan Amir Journal: JNCI Cancer Spectr Date: 2019-05-11
Authors: Ana Godoy-Ortiz; Alfonso Sanchez-Muñoz; Maria Rosario Chica Parrado; Martina Álvarez; Nuria Ribelles; Antonio Rueda Dominguez; Emilio Alba Journal: Front Oncol Date: 2019-10-29 Impact factor: 6.244