铂耐药卵巢癌治疗排序的新时代：整合免疫治疗、抗体药物偶联物与靶向治疗。
完整摘要 · 中文译文
铂耐药卵巢癌（PROC）历来采用序贯非铂类化疗治疗，并在适当时加用贝伐珠单抗。随着帕博利珠单抗联合每周紫杉醇（加或不加贝伐珠单抗）（KEYNOTE-B96）、mirvetuximab soravtansine（MIRV）用于FRα高表达疾病（MIRASOL），以及relacorilant联合白蛋白结合型紫杉醇（ROSELLA）的阳性随机III期数据，治疗格局已有所扩展。曲妥珠单抗 deruxtecan（T-DXd）在既往接受过治疗的HER2表达卵巢癌中也显示出显著活性，尽管其卵巢癌队列规模较小、非随机化，且不限于PROC。这些试验入组了不同的人群，并未建立跨试验的疗效等级排序。因此，我们回顾了导致KEYNOTE-B96的免疫治疗发展历程，将新策略与既定的PROC治疗进行比较，区分III期证据与监管批准及常规可及性，并提出一个基于证据的治疗选择和序贯治疗框架。该框架在考虑生物标志物合格性、既往治疗、残留毒性、治疗和经济负担、患者优先事项以及后续治疗可行性的同时，优先考虑当前的治疗机会。
完整摘要 · 英文原文
Platinum-resistant ovarian cancer (PROC) has historically been treated with sequential non-platinum chemotherapy, with bevacizumab added when appropriate. The therapeutic landscape has expanded with positive randomized phase III data for pembrolizumab plus weekly paclitaxel with or without bevacizumab (KEYNOTE-B96), mirvetuximab soravtansine (MIRV) in FRα-high disease (MIRASOL), and relacorilant plus nab-paclitaxel (ROSELLA). Trastuzumab deruxtecan (T-DXd) has also shown substantial activity in previously treated HER2-expressing ovarian cancer, although its ovarian cohort was small, nonrandomized, and not restricted to PROC. These trials enrolled different populations and do not establish a cross-trial efficacy hierarchy. We therefore review the development of immunotherapy leading to KEYNOTE-B96, compare newer strategies with established PROC treatments, distinguish phase III evidence from regulatory approval and routine availability, and propose an evidence-informed framework for treatment selection and sequencing. The framework prioritizes current treatment opportunity while accounting for biomarker eligibility, prior treatment, residual toxicity, treatment and financial burden, patient priorities, and the feasibility of later-line therapy.