Fac Rev

Recent advances in neoadjuvant therapy for breast cancer

Potter DA, Herrera-Ponzanelli CA, Hinojosa D, Castillo R, Hernandez-Cruz I, Arrieta VA, Franklin MJ, Yee D

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.

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