Surrogate marker analysis in cancer clinical trials through time-to-event mediation techniques.
Stat Methods Med Res
; 27(11): 3367-3385, 2018 11.
Article
en En
| MEDLINE
| ID: mdl-28425345
ABSTRACT
The meta-analytic approach is the gold standard for validation of surrogate markers, but has the drawback of requiring data from several trials. We refine modern mediation analysis techniques for time-to-event endpoints and apply them to investigate whether pathological complete response can be used as a surrogate marker for disease-free survival in the EORTC 10994/BIG 1-00 randomised phase 3 trial in which locally advanced breast cancer patients were randomised to either taxane or anthracycline based neoadjuvant chemotherapy. In the mediation analysis, the treatment effect is decomposed into an indirect effect via pathological complete response and the remaining direct effect. It shows that only 4.2% of the treatment effect on disease-free survival after five years is mediated by the treatment effect on pathological complete response. There is thus no evidence from our analysis that pathological complete response is a valuable surrogate marker to evaluate the effect of taxane versus anthracycline based chemotherapies on progression free survival of locally advanced breast cancer patients. The proposed analysis strategy is broadly applicable to mediation analyses of time-to-event endpoints, is easy to apply and outperforms existing strategies in terms of precision as well as robustness against model misspecification.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
/
Biomarcadores
/
Supervivencia sin Enfermedad
Tipo de estudio:
Clinical_trials
Límite:
Female
/
Humans
Idioma:
En
Revista:
Stat Methods Med Res
Año:
2018
Tipo del documento:
Article
País de afiliación:
Bélgica