Abstract
Simple SummaryIn the treatment of patients with breast cancer, post-neoadjuvant approaches represent an attractive opportunity to improve patient outcomes by stratifying adjuvant treatment according to tumor response. Thus, these concepts represent a step towards our vision of individualized adaptive tumor treatment. Although apparently in its early stages, increasing evidence indicates an important change to our historical treatment strategies.Neoadjuvant chemotherapy enables close monitoring of tumor response in patients with breast cancer. Being able to assess tumor response during treatment provides an opportunity to evaluate new therapeutic strategies. Thus, for triple-negative breast tumors, it was demonstrated that additional immunotherapy could improve prognosis compared with chemotherapy alone. Furthermore, adjuvant therapy can be escalated or de-escalated correspondingly. The CREATE-X trial randomly assigned HER2-negative patients with residual tumor after neoadjuvant therapy to either observation or capecitabine. In HER2-negative patients with positive BRCA testing, the OlympiA study randomly assigned patients to either observation or olaparib. HER2-positive patients without pathologic remission were randomly assigned to trastuzumab or trastuzumab–emtansine within the KATHERINE study. These studies were all able to show an improvement in oncologic outcome associated with the escalation of therapy in patients presenting with residual tumor after neoadjuvant treatment. On the other hand, this individualization of therapy may also offer the possibility to de-escalate treatment, and thereby reduce morbidity. Among WSG-ADAPT HER2+/HR-, HER2-positive patients achieved comparable results without chemotherapy after complete remission following neoadjuvant treatment. In summary, the concept of post-neoadjuvant therapy constitutes a great opportunity for individualized cancer treatment, potentially improving outcome. In this review, the most important trials of post-neoadjuvant therapy are compiled and discussed.
Highlights
Neoadjuvant systemic therapy was generally reserved for unresectable or inflammatory breast cancer
A subsequent phase III trial by the ECOG-ACRIN group failed to demonstrate the superiority of post-neoadjuvant treatment with carboplatin or cisplatin over capecitabine in triple-negative breast cancer patients with residual disease after neoadjuvant chemotherapy [10]
The German GeparNuevo study was able to demonstrate a non-significant improvement in the pCR rate, and even a significantly improved survival rate, in primary triple-negative breast cancer patients with the addition of durvalumab to neoadjuvant chemotherapy [11]. These results have been confirmed within the phase III Keynote 522 trial for high-risk, early-stage and triple-negative breast cancers treated with neoadjuvant chemotherapy, with or without pembrolizumab [3]
Summary
Neoadjuvant systemic therapy was generally reserved for unresectable or inflammatory breast cancer. The trial showed a strong correlation between tumor response to the primary systemic therapy and oncologic outcomes This allowed trialists to dichotomize the patient population into two strata and apply adjuvant treatment (post-neoadjuvant) according to the pathological response to the neoadjuvant systemic treatment. This strategy permits studying new systemic therapies or new combinations of treatment modalities. More important is that we can use this refined or individualized prognosis assessment to either escalate postoperative therapy (if the risk of recurrence remains high) or to de-escalate it (if the prognosis is favorable) Since such a risk-adapted adjuvant treatment is only possible through a neoadjuvant application of systemic therapy, this is referred to as post-neoadjuvant therapy.
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