摘要：近几年来，靶向叶酸受体α（FRα）的新药（例如mirvetuximab soravtansine-gynx）为FRα高表达的铂耐药上皮性卵巢癌、输卵管癌或原发性腹膜癌经治患者带来新希望；然而没有该生物标志物的患者仍然需要其他选择。根据近期发布的随机、全球多中心
近几年来，靶向叶酸受体α（FRα）的新药（例如mirvetuximab soravtansine-gynx）为FRα高表达的铂耐药上皮性卵巢癌、输卵管癌或原发性腹膜癌经治患者带来新希望；然而没有该生物标志物的患者仍然需要其他选择。根据近期发布的随机、全球多中心、开放标签III期ROSELLA试验结果，在既往接受过1-3线全身抗癌治疗（包括贝伐珠单抗）的复发性、铂耐药、高级别浆液性上皮性卵巢癌患者中，选择性糖皮质激素受体（GR）拮抗剂Relacorilant联合白蛋白结合型紫杉醇化疗组相比对照组（单用化疗）改善无进展生存（PFS），经盲态独立中心审查（BICR）评估的中位PFS分别为6.5个月和5.5个月（风险比[HR]为0.70；P=0.008）。中期分析显示，总生存期（OS）在临床上显著改善（HR=0.69，中位数分别为16.0个月vs 11.5个月，P=0.01）。各研究组的不良事件 (AE) 相似，Relacorilant + 白蛋白结合型紫杉醇方案耐受性良好，未出现新的安全信号。最常见的报告不良事件是白蛋白结合型紫杉醇的已知毒性：贫血 (58%)、中性粒细胞减少 (56%) 和恶心 (39%)。
在2025年美国临床肿瘤学会（ASCO）年会上，来自匹兹堡大学医学院、麦吉妇女医院妇科肿瘤组的Alexander Olawaiye教授将以口头报告（摘要号LBA5507）形式汇报更详细的研究数据。在报告发布前，《肿瘤瞭望》现场特邀Olawaiye教授就ROSELLA研究的发现与临床意义进行探讨。
《肿瘤瞭望》：根据ROSELLA研究的最新结果（LBA5507），Relacorilant联合白蛋白结合型紫杉醇治疗铂耐药卵巢癌患者的疗效和安全性如何？
Dr. Olawaiye：ROSELLA试验有两个主要终点：一是无进展生存期；二是总生存期。两个主要终点的意思是，只要其中一个终点呈阳性，试验结果就会呈阳性。无进展生存终点的结果已经出来了，这就是我们将在2025 ASCO会议发布的内容。Relacorilant组和对照组的PFS差异具有非常显著的统计学意义，PFS风险比为0.7，有利于Relacorilant组。这意味着疾病进展或死亡风险降低了30%。
ROSELLA试验的总生存期数据尚不成熟，但我们已经开始看到生存曲线分离。总生存期的风险比为0.69，这意味着死亡风险降低了 31%。这些研究发现非常引人注目，也非常令人兴奋。
Dr. Olawaiye: This trial had a dual primary endpoint. One, progression-free survival. Two, overall survival. What dual primary endpoints meant is if either endpoint was positive, the trial would be positive. So, the progression-free survival endpoint has already read out, and that is what we presented, there is a highly statistically significant difference in progression free survival between the two arms of the trial. The hazard ratio for progression free survival is 0.7 in favor of the relacorilant arm. This represents a 30% reduction in the hazard of progression of disease or death. The overall survival data is not yet mature, but we have already begun to see the curves separate. The hazard ratio for overall survival is 0.69, which again, is a 31% reduction in the hazard of death. These findings are very compelling, and they are very exciting.
《肿瘤瞭望》：鉴于FRα检测组织样本的时效性挑战，Relacorilant方案不需要生物标志物筛选患者，这是否会对资源有限的地区特别有利？
Dr. Olawaiye：是的，这正是Relacorilant方案令人兴奋的地方。不需要生物标志物的筛选，这是一件好事。靶向FRα的药物治疗卵巢癌很有效，然而，只有一部分患者的癌症表达高水平的FRα，因此Relacorilant这种新药的独特之处在于无需进行生物标志物筛选。如果患者患有铂耐药卵巢癌，当该组合方案可用时，他们有资格接受Relacorilant 与白蛋白结合型紫杉醇 (nab-paclitaxel) 的联合治疗。正如您所知，该药物尚未获得 FDA 批准，但我们对此充满希望。
Dr. Olawaiye: Yes. Again, that is what is exciting about it. For biomarker selection, that is a good thing. The folate receptor-alpha (FRα) targeting drug is very good, however, only a percentage of patients’ cancer express high levels of FRα, so the uniqueness of this new medication, relacorilant, is that there is no necessity for biomarker selection. If the patient has platinum-resistant ovarian cancer, they are eligible to be treated with relacorilant combined with nab-paclitaxel when that combination is available. As you know, it is not yet FDA-approved, but we are hopeful.
《肿瘤瞭望》：作为糖皮质激素受体拮抗剂，Relacorilant治疗对新发糖尿病/高血压是否有影响？
Dr. Olawaiye：糖皮质激素信号传导实际上是促糖尿病发生的，这意味着如果某人糖皮质激素暴露过量，就会干扰正常糖代谢的能力。例如，如果给糖尿病患者服用糖皮质激素，他们的糖尿病就会变得非常难以控制。Relacorilant的作用机制则相反，其阻断糖皮质激素信号传导。虽然我们没有研究将Relacorilant作为糖尿病的治疗方法，但根据它的生物学原理，糖尿病或糖尿病控制困难不会成为Relacorilant的副作用。Relacorilant甚至可能有助于控制糖尿病。
Dr. Olawaiye: Glucocorticoid signaling is actually pro-diabetic, which means if somebody has too much glucocorticoid exposure, it disturbs the ability to metabolize sugar properly. For instance, if you give diabetic patients glucocorticoids, their diabetes becomes very difficult to control. Relacorilant functions in the opposite way. It blocks glucocorticoid signaling. Even though we did not study this as a treatment for diabetes, the biology of it is that diabetes or difficulty with diabetes control would not be a problem as a side effect of relacorilant. It may even help diabetes control.
《肿瘤瞭望》：2025年ASCO发布了大量关于妇科肿瘤的研究结果，您认为哪些研究会对临床实践产生重大影响？
Dr. Olawaiye：我认为ROSELLA是其中一项具有临床影响力的研究，因为，请记住，Relacorilant是治疗卵巢癌的首创（first-in-class）新药，意味着这是一种既往我们从未见过的药物。在其他即将在本次会议汇报的试验中，许多研究的是已在使用的药物——这些药物要么原本用于卵巢癌但现与其他药物联用，要么是已在其他癌症类型中确立疗效的药物。这项研究及其之前的两项先行研究代表了Relacorilant首次用于治疗任何癌症，我们对ROSELLA研究发现感到非常兴奋，并希望Relacorilant能成为铂耐药卵巢癌治疗的新标准。
Dr. Olawaiye: ROSELLA is one of those studies that I think is going to be clinically impactful, because, remember that relacorilant is a first-in-class drug in ovarian cancer. We have never seen anything like it before. The other trials were that were presented, studied drugs that are already in use, either in ovarian cancer and now modified with another agent, or are already established in other cancers. This study and its previous two forerunners represent the first time relacorilant would be studied in any cancer. We are so excited about the findings, and we are hoping this is going to be a new standard in platinum-resistant ovarian cancer treatment.
参考文献
1.Olawaiye A, et al. ROSELLA: a phase 3 study of relacorilant in combination with nab-paclitaxel vs nab-paclitaxel monotherapy in patients with platinum-resistant ovarian cancer (GOG-3073, ENGOT-ov72). 2025 ASCO, LBA5507.
来源：肿瘤瞭望
