Department of Medical Oncology, Dana-Farber Cancer Institute.
Harvard Medical School, Boston, Massachusetts.
Curr Opin Oncol. 2022 Nov 1;34(6):623-634. doi: 10.1097/CCO.0000000000000893. Epub 2022 Aug 19.
Triple-negative breast cancer (TNBC) has been conventionally associated with poor prognosis, as a result of limited therapeutic options. In the early setting, prognosis is informed by clinical-pathological factors; for patients receiving neoadjuvant treatments, pathological complete response (pCR) is the strongest factor. In this review, we mapped the landscape of clinical trials in the postneoadjuvant space, and identified three patterns of clinical trial design.
For patients at higher risk, effective postneoadjuvant treatments are of paramount importance to address a high clinical need. Postneoadjuvant risk-adapted treatments have demonstrated to improve survival in patients at high of recurrence.
Patients at high risk have indication for adjuvant treatment intensification, informed by baseline clinical, pathological or molecular factors (type 1 approach), on the presence, extent and molecular characteristics of the residual disease at the time of surgery (type 2) or on risk factors assessed in the postsurgical setting (type 3), for example, circulating tumour DNA. Most of the past trials were based on type 2 approaches, for example, with capecitabine and Olaparib. Few trials were based on a type 1 approach, notably pembrolizumab for early TNBC. The clinical validity of type 3 approaches is under investigation in several ongoing trials.
三阴性乳腺癌(TNBC)由于治疗选择有限,传统上与预后不良相关。在早期,预后取决于临床病理因素;对于接受新辅助治疗的患者,病理完全缓解(pCR)是最强的因素。在这篇综述中,我们绘制了新辅助后临床试验的全景图,并确定了三种临床试验设计模式。
对于风险较高的患者,有效的新辅助后治疗对于满足高临床需求至关重要。新辅助后风险适应治疗已证明可改善高复发风险患者的生存。
高风险患者有指征进行辅助治疗强化,这取决于基线临床、病理或分子因素(1 型方法)、手术时残留疾病的存在、程度和分子特征(2 型方法)或术后评估的风险因素(3 型方法),例如循环肿瘤 DNA。过去的大多数试验都是基于 2 型方法,例如卡培他滨和奥拉帕利。只有少数试验基于 1 型方法,特别是帕博利珠单抗用于早期 TNBC。几种正在进行的试验正在研究 3 型方法的临床有效性。