Relationship between complete pathologic response to neoadjuvant chemotherapy and survival in triple negative breast cancer
A partir de données issues d'un essai de traitement néoadjuvant chez des patientes atteintes d'un cancer du sein triplement négatif, cette étude de simulation évalue l'association entre le taux de réponse pathologique complète et la survie globale
Background: Pathologic complete response (pCR) to neoadjuvant chemotherapy reflects the cytotoxic efficacy of a drug, but patient survival is influenced by many other factors. The purpose of this study was to assess the relationship between increased pCR rate and trial-level survival benefit in triple negative breast cancer (TNBC).
Methods: We used bootstrap resampling from a neoadjuvant trial to simulate trials with different pCR rates. We used estimates from AdjuvantOnline to simulate trial populations with different baseline prognosis and estimated survival improvements associated with changes in pCR rate.
Results: Assuming that survival is similar for patients with pCR regardless of treatment arm, a linear relationship exists between increasing pCR rate and increasing RFS. The slope is equal to the difference in survival between those with pCR and RD which in turn is influenced by (i) the baseline prognosis of the trial population, (ii) interactions between prognostic variables and pCR, and (iii) the efficacy of the post-neoadjuvant therapies. For example, if the pCR rates are 30% and 60% (OR=3.5) and the 10-year RFS of the control arm is 0.74, the trial would require 3550 patients per arm, whereas if the RFS is 0.54 the trial would only require 425 patients per arm to detect significant survival benefit.
Conclusions: We provide a framework for understanding the relationship between pCR and overall survival benefit that can help inform the design of neoadjuvant trials aiming to demonstrate improved survival from a regimen that results in higher pCR rate.
Clinical Cancer Research , résumé, 2015