Neoadjuvant (preoperative) approach to breast cancer treatment has become widely accepted. Traditionally, the primary objective of neoadjuvant treatment is to improve subsequent surgical intervention and the effectiveness is often evaluated by its ability to achieve complete pathological response (pCR) and the eradication of the malignant disease in the breast and axillary lymph nodes. More recently, neoadjuvant treatment has also become recognized as an in vivo, preoperative” window of opportunity” to explore the efficacy of novel agents such as immunotherapies where several tumor biomarkers are also routinely collected to quantify antitumor immunity. However, one challenge to combine the traditional pCR and efficacy biomarkers is that these tumor biomarkers are only partially available and cannot be measured in patients who have achieved pCR. In this article, a stepwise hypothesis testing procedure is proposed to combine a continuous tumor biomarker with the conventional binary endpoint in a two-arm randomized phase II superiority trial to improve statistical power. The operating characteristics of the proposed procedure are illustrated with a real-world example and the performance is also evaluated numerically.

乳腺癌治疗的新辅助（术前）方法已被广泛接受。传统上，新辅助治疗的主要目标是改善后续的手术干预，其有效性通常通过其实现完全病理反应（pCR）和根除乳腺和腋窝淋巴结恶性疾病的能力来评估。最近，新辅助治疗也被认为是一种体内、术前的“机会之窗”，可以探索免疫疗法等新型药物的疗效，其中还常规收集多种肿瘤生物标志物来量化抗肿瘤免疫力。然而，将传统的 pCR 和疗效生物标志物结合起来的一个挑战是，这些肿瘤生物标志物仅部分可用，无法在已达到 pCR 的患者中进行测量。在本文中，提出了一种逐步假设检验程序，以在双臂随机 II 期优效性试验中将连续肿瘤生物标志物与传统二元终点相结合，以提高统计功效。拟议程序的操作特性通过一个真实世界的例子进行说明，并且还对性能进行了数值评估。