Neoadjuvant trials for early
breast cancer have accelerated the identification of novel active agents, enabling streamlined conduct of registration trials with fewer subjects. Measurement of neoadjuvant
drug effects has also enabled the identification of patients with high risk of distant recurrence and has justified development of additional adjuvant approaches to improve outcomes. Neoadjuvant evaluation of new drugs was significantly improved by the introduction of
pathologic complete response (pCR) rate as a quantitative
surrogate endpoint for distant disease-free survival (DDFS) and event free survival (EFS). The neoadjuvant phase 2 platform trial I-SPY 2 simultaneously tests multiple drugs across multiple
breast cancer subtypes using Bayesian methods of adaptive randomization for assessment of
drug efficacy. In addition to the pCR endpoint, the I-SPY 2 trial has demonstrated that the
residual cancer burden (RCB) score measures gradations of
tumor response that correlate with DDFS and EFS across treatments and subtypes. For HER2-positive and
triple-negative breast cancers that have failed to attain pCR with
neoadjuvant chemotherapy (NAC), effective modifications of adjuvant treatment have improved outcomes and changed the standard of care for these subtypes.
Neoadjuvant therapy is therefore preferred for stage II and III, as well as some stage I, HER2-positive and triple-negative
tumors. Neoadjuvant endocrine
therapy (NET) strategies have also emerged from innovative trials for stage II and III
estrogen receptor (ER)-positive/HER2-negative
tumors, as in the ALTERNATE trial. From neoadjuvant trials, opportunities have emerged to de-escalate
therapy on the basis of metrics of response to
chemotherapy or hormonal
therapy.
Neoadjuvant therapy for early
breast cancer is therefore emerging as a promising approach to accelerate new
drug development, optimize treatment strategies, and (where appropriate) de-escalate
neoadjuvant therapy.