铂耐药卵巢癌是卵巢癌治疗中公认的临床难题：患者预后差、治疗选择有限，延长生存与保障生活质量如何取舍，始终困扰着临床实践。随着抗体药物偶联物（ADC）、免疫治疗与PARP抑制剂等新型药物不断涌现，铂耐药卵巢癌的序贯治疗策略也面临新的思考。
编者按：铂耐药卵巢癌是卵巢癌治疗中公认的临床难题：患者预后差、治疗选择有限，延长生存与保障生活质量如何取舍，始终困扰着临床实践。随着抗体药物偶联物（ADC）、免疫治疗与PARP抑制剂等新型药物不断涌现，铂耐药卵巢癌的序贯治疗策略也面临新的思考。
第29届中国临床肿瘤学会（CSCO）学术年会于2026年9月16日至19日在山东济南召开。本届年会以“守正规范，数智创新”为主题，汇聚全球肿瘤领域知名专家学者，分享前沿研究成果与临床经验，促进学术交流与合作。大会现场，肿瘤瞭望特邀新加坡国立大学癌症中心（NCIS）高级顾问肿瘤内科医生David Tan教授，围绕铂耐药卵巢癌的治疗目标、新型药物时代的序贯治疗策略，以及亚洲人群药物耐受性与国际方案应用等热点话题展开深度对话。以下为本次采访的精彩内容。
肿瘤瞭望：目前，铂耐药卵巢癌仍是临床上面临的一大挑战。在您看来，现阶段铂耐药卵巢癌治疗的首要目标，是延长生存期，还是平衡生活质量？
David Tan 教授：我认为这是一个很好的问题。事实上，我们两个目标都想要。铂耐药卵巢癌患者——或者说任何形式的复发性卵巢癌患者——往往承受着相当高的症状负担。她们多有腹部不适的问题，也常常面临许多心理挑战，其中约35%的患者可能存在重度抑郁。因此，我们真正需要努力去做的，首先是改善症状。这意味着，无论给予何种治疗，都需要获得更好的治疗缓解，而且这种缓解必须是持久的。我认为，缓解的持久性能够改善生活质量，也能改善患者的情绪和心理健康。所以在我看来，对铂耐药疾病而言，良好而有效的治疗应当同时改善生活质量、延长无进展生存期。
Oncology Frontier：At present, platinum-resistant ovarian cancer remains a clinical challenge. In your opinion, is the primary goal of treatment for platinum-resistant ovarian cancer at this stage to prolong survival or to balance quality of life?
Prof. David Tan：I think that's a great question. I think the reality is that we want to do both. Patients with platinum-resistant ovarian cancer — or any form of recurrent ovarian cancer, for that matter — often have quite a high symptomatic burden. They have a lot of problems with abdominal discomfort, and they often have a lot of psychological challenges as well; about 35% of them may have severe depression. So really, what we need to try to do is, first of all, improve the symptoms. And that means we need a better response to whatever treatment we give them, but that response needs to be durable as well. And I think with the durability of response, we're going to be able to improve quality of life and improve their emotional and psychological health as well.
So in my view, good and effective treatment for platinum-resistant disease should be both improving quality of life and also progression-free survival.
肿瘤瞭望：随着抗体药物偶联物（ADC）、免疫治疗和PARP抑制剂等新型药物不断涌现，对于铂耐药卵巢癌患者，我们应如何设计序贯治疗策略？
David Tan 教授：我认为当前药物研发方式令人欣喜的一点是，未来许多患者将拥有更多治疗选择。但一个关键问题是：这些药物应如何用于患者、何时使用，以及是否需要考虑合理的序贯安排。
许多新药，例如ADC，正被引入卵巢癌更早期的治疗阶段。过去很长一段时间里，我们在一线治疗中只有卡铂和紫杉醇，疾病进展后使用PARP抑制剂，之后再进行更多化疗。但如果ADC未来投入临床应用，我们可能将面对“ADC之后”的治疗场景，这意味着患者人群将完全不同，这些肿瘤的生物学特性也可能已经彻底改变。
因此，这些新的癌症亚群、亚型及其生物学特性将如何演变，将是一个非常关键的问题。就目前而言，我认为在相关场景下我们必须非常倚重生物标志物。例如，对于PARP抑制剂，HRD（同源重组缺陷）状态当然非常重要。在部分ADC中，我们认为生物标志物至关重要，例如T-DXd（德曲妥珠单抗）这类药物中的HER2表达，以及mirvetuximab soravtansine（靶向叶酸受体α的ADC）所对应的叶酸受体α表达。但在更新的ADC试验中，蛋白质表达似乎并非那么关键。我认为我们需要等待这些Ⅱ期研究的结果公布，才能更好地理解这些生物标志物如何帮助筛选合适的患者人群。除此之外，我们确实还没有很好的答案，只能等待这些数据公布，再在未来针对这些新出现的患者亚群逐一应对。
Oncology Frontier：With the continuous emergence of new agents such as ADCs, immunotherapies, and PARP inhibitors, how should we design sequential treatment strategies for patients with platinum-resistant ovarian cancer?
Prof. David Tan：I think the great thing about the way drugs are being developed right now is that many of our patients will have more options in the future. But there is an important question about how they should be treated and when they should be treated with these agents, and also whether or not you need to think about sequencing them appropriately.
Many of the newer drugs, like the antibody–drug conjugates, are now being brought into the earliest treatment settings for patients with ovarian cancer. As you know, for a long time, all we had was carboplatin and paclitaxel in the first-line setting, followed by PARP inhibitors and then more chemotherapy when they progress. But if ADCs are now going to be used in the future, we may be looking at the post-ADC setting, which means it's going to be a whole different population of patients, and the biology of those tumors may have completely shifted as well.
So how these new subsets and subtypes of cancers, and their biology, are going to emerge is going to be a really important question. For now, I think we just have to rely very strongly on biomarkers where they are relevant. So I think for PARP inhibitors, certainly the HRD status is really important. There are certain ADCs where we think the biomarkers are crucial — like HER2 expression in drugs such as T-DXd, for example, and folate receptor alpha expression with mirvetuximab soravtansine. But with the newer trials in the newer ADCs, where it does appear that the expression of the protein may not be so crucial, I think we have to wait for those phase II studies to read out before we understand better how those biomarkers can help to define the right patient population as well. But I think beyond that, we really don't have any good answers, and we can only wait for these data to read out, and then address these new subsets of patients as they emerge in the future.
肿瘤瞭望：亚洲卵巢癌患者与西方人群在药物耐受性和遗传特征方面是否存在差异？将国际治疗方案应用于中国患者时，需要注意哪些问题？
David Tan 教授：我首先要说的是，如今开展药物研发，所有药企都知道剂量优化已被置于非常重要的位置，因为仅仅完成标准Ⅰ期研究、得出推荐的Ⅱ期剂量是不够的。有时在早期Ⅰ期试验中，你可能会得到两三个你认为疗效相当的剂量，但你需要进一步了解耐受性。我认为，这正是越来越多的剂量优化研究需要纳入来自不同国家、不同种族患者的原因。试验中应该有中国患者、白种人患者，也应该有来自中东的患者。因为归根结底，要想了解毒性和耐受性，只有让试验纳入更广泛、更多样化的患者群体，才能真正为任何一种药物、为不同患者人群确定安全可耐受的剂量。
我们现在已经知道，与其他人群相比，中国患者可能对某些化疗药物的耐受性存在差异。例如在过去，这种情况往往要等药物获批之后才被发现。当我们开始在患者中使用这些药物时，会突然发现原始研究未曾报告的新副作用，这纯粹是因为原始研究的试验人群缺乏足够的多样性。
我们看到这种情况正在改变，这也是为什么作为亚洲的团队，我们正努力组建新的试验组织和网络，与产业界开展更多合作，确保我们的患者也能被纳入这些试验。我相信，当我们获得更多这样的数据后，我们管理中国患者、亚洲患者的方式也将得到改善，因为我们能更深入地了解药物的毒性，以及适合这些患者的合适剂量。
Oncology Frontier：Are there differences in drug tolerability and genetic characteristics between Asian ovarian cancer patients and Western populations? What should be noted when applying international regimens to Chinese patients?
Prof. David Tan：The first thing I would say is that when you do drug development these days, as any company will know, there is now great importance placed on dose optimization, because it is not enough just to do your standard phase I study and get to a recommended phase II dose. Sometimes when you do these in the early phase I trials, you might come up with two or maybe three doses that you think may have equivalent efficacy. But you need to understand a bit more about the tolerance. And this is where I feel that more and more of these dose optimization studies need to also involve patients from different countries and different ethnic groups as well. So there should be Chinese patients, there should be Caucasian patients, there should be patients from the Middle East. Because ultimately, when you want to understand toxicity and tolerance, it's only when you have a wider, diverse group of patients in your trials that you can truly define what a safe, tolerable dose is for various populations of patients, for any one drug.
Now we already know that Chinese patients may not tolerate some chemotherapy agents compared with other populations. For example, in the past, that has only really been seen once the drugs have been approved. And when we start using these drugs in our patients, we suddenly find new side effects that were not reported in the original studies, purely because the original studies didn't include enough diversity in terms of their trial patient population.
We see that changing now, and that's also part of the reason why, as a group in Asia, we are trying to form new trial groups and networks in order to collaborate more with industry, to make sure that our patients are represented in these trials as well. And I think when we have more of that data, the way we manage our Chinese patients and our Asian patients is also going to be improved, because we understand more about the toxicity and the appropriate dose for these patients.
专家介绍
David Tan 教授
职务概况
新加坡国立大学癌症研究所高级顾问肿瘤内科医师
新加坡国立大学杨潞龄医学院医学系副教授
新加坡国立大学癌症科学研究所首席研究员
临床与研究方向
主要临床与研究领域为妇科肿瘤、精准肿瘤学及早期临床试验。已发表100余篇同行评审科学论文，并多次因研究成果获奖。
学术组织任职
新加坡妇科肿瘤组（GCGS）的创始主席。曾任GCGS宫颈癌研究网络（CCRN）主席，现任GCIG执行董事会成员。
亚太妇科肿瘤试验组（APGOT）的创始主席，目前担任APGOT方案审查委员会主席。