Study objectives and endpoints.

BackgroundCurrent evidence on circulating tumor DNA (ctDNA) in the adjuvant setting of early breast cancer (eBC) confirms its high prognostic value. CtDNA-positive patients without radiographic signs of relapse show reduced disease-free and overall survival. Secondary adjuvant treatment intervention studies represent a new appealing therapeutic option.MethodsWe present SURVIVE HERoes, a phase III randomized clinical trial of the potent antibody-drug conjugate trastuzumab deruxtecan versus standard of care (SoC) in patients with HER2 positive or HER2 low eBC and molecular residual or recurrent disease (ctDNA positive, cM0) after primary therapy. The primary endpoint is the ctDNA clearance rate after 12 months of therapeutic intervention. A total of 180 study participants will be enrolled and randomized in a 2:1 ratio to receive trastuzumab deruxtecan or SoC therapy. The trial is accompanied by an extensive translational research project.DiscussionTreating ctDNA positive patients without radiographic signs of recurrence is a novel approach. If SURVIVE HERoes and similar studies targeting MRD will be positive, this may lead the way to a new molecular understanding of breast cancer stages and individualized therapy and may open a new therapeutic window for cure.研究背景：目前针对早期乳腺癌（early breast cancer, eBC）辅助治疗场景中的循环肿瘤DNA（circulating tumor DNA, ctDNA）的相关研究证据已证实其具备较高的预后价值。未出现影像学复发征象的ctDNA阳性患者，其无病生存期与总生存期均显著缩短。针对此类患者开展的二次辅助治疗干预研究，正成为极具吸引力的新型治疗选择。 研究方法：本研究介绍SURVIVE HERoes试验，这是一项Ⅲ期随机临床试验，旨在对比强效抗体偶联药物德曲妥珠单抗（trastuzumab deruxtecan）与标准治疗方案（standard of care, SoC）在经初始治疗后、存在分子学残留或复发性疾病（ctDNA阳性、临床分期cM0）的HER2阳性或HER2低表达早期乳腺癌患者中的疗效。本试验的主要终点为治疗干预12个月后的ctDNA清除率。研究计划共纳入180名受试者，按2:1的比例随机分配至德曲妥珠单抗组或标准治疗组。本试验同步配套开展大规模转化研究项目。 研究讨论：针对无影像学复发征象的ctDNA阳性患者实施治疗属于一种创新性治疗策略。若SURVIVE HERoes试验及其他针对微小残留病（minimal residual disease, MRD）的相关研究取得阳性结果，将有望推动乳腺癌分期的分子层面认知革新与个体化治疗方案的发展，并为乳腺癌治愈开辟全新的治疗途径。