摘要：9月6日-9日，国际肺癌研究协会（IASLC）举办的2025年世界肺癌大会（WCLC）在西班牙巴塞罗那举行，多项改变临床实践的研究结果相继公布，大会特设“Highlights of the Day”专场，旨在回顾当日领域重磅研究进展。在会议现场，《肿瘤瞭望》前

9月6日-9日，国际肺癌研究协会（IASLC）举办的2025年世界肺癌大会（WCLC）在西班牙巴塞罗那举行，多项改变临床实践的研究结果相继公布，大会特设“Highlights of the Day”专场，旨在回顾当日领域重磅研究进展。在会议现场，《肿瘤瞭望》前方记者邀请“Highlights of the Day - Sunday Abstracts”专场的点评专家、德国 Grosshansdor 肺科医院Martin Reck教授对2025 WCLC重要研究予以点评。

专家简介

Martin Reck 教授

德国Grosshansdorf肺科诊所胸部肿瘤科主任兼临床试验部门主任

德国肺癌研究中心（DZL）肺癌领域的PI

德国肺癌工作组、德国癌症协会、德国肺病学会、国际肺癌研究协会、欧洲肿瘤内科学会 (ESMO) 和美国临床肿瘤学会 (ASCO) 的成员

参与了多项重要的临床试验，旨在探索晚期肺癌的新疗法，例如维持治疗或靶向治疗，以及关键的生物标志物试验，主要研究兴趣包括非小细胞肺癌的靶向治疗、小细胞肺癌的新疗法、恶性胸膜间皮瘤的现代疗法，以及与预测标志物相关的转化研究

肿瘤瞭望：2025 WCLC全体大会发布了多项重要研究，能否分享您对研究结果的思考？

Martin Reck：我是来自德国北部一家专业肺癌中心的肺科医生Martin Reck，很荣幸能介绍本届WCLC全体大会的重点研究。我认为有三项尤为重要的报告值得关注。

第一项报告是FLAURA2试验的更新结果（摘要PL02.06）。该研究评估了在EGFR突变非小细胞肺癌（NSCLC）患者中，奥希替尼联合化疗对比奥希替尼单药治疗的疗效与安全性。既往数据已显示联合治疗组无进展生存期（PFS）显著改善。而在2025年WCLC大会上，我们看到了总生存期（OS）的更新数据：与奥希替尼单药组相比，联合治疗组中位OS显著延长。此外，不良事件没有增加，也就是说，没有新的副作用。总体而言，奥希替尼联合化疗显示出可接受的耐受性。

第二项报告聚焦于EGFR突变NSCLC的二线治疗（摘要PL02.12）。HARMONi试验探索了在三代EGFR-TKI治疗后进展的EGFR阳性NSCLC患者中，依沃西单抗联合化疗对比单纯化疗的疗效。该研究此前已证实联合方案可带来PFS显著延长。本次WCLC更新数据进一步确认了PFS获益，也发布了OS数据。尽管未达到统计学显著性，但OS获益趋势非常明确。在安全性方面，包括我们特别关注的免疫相关不良事件和抗血管生成相关不良事件，此次更新未发现新的安全信号。

第三项非常重要的摘要关注了另一类致癌基因导致的癌症，即ROS1阳性的非小细胞肺癌患者（摘要PL02.15）。ARROS-1试验中，新型ROS1抑制剂Zidesamtinib用于TKI经治的晚期或转移性ROS1阳性NSCLC患者有相当显著的临床疗效，不仅在缓解率方面，而且在无进展生存期方面也表现出色。对于已经接受过先进TKI（瑞普替尼等）治疗的患者也是如此。再加上其具有非常良好的安全性，这显然是一种未来研发中备受关注的药物。

Martin Reck: My name is Martin Reck. I'm coming from northern Germany. I'm a pulmonologist by training. I am working in a dedicated lung cancer Center in the North of Germany, and it's my pleasure to be here with you at the WCLC 2025 in Barcelona.

I have the pleasure to talk about the highlights of the last plenary session, and I think we have three really important presentations seen there. The first one has been the update of the FLAURA2 trial, investigating the combination of chemotherapy and osimertinib versus osimertinib alone in EGFR receptor mutated patients. We already know that there is a significant improvement in progression free survivor. Now we have seen the overall survival update in 2025 WCLC and we do see also a significant prolongation of overall survival and a meaningful prolongation of overall survival in favor of the combination of osimertinib and chemotherapy. Along with that, what we also have seen the outcome that there hasn't been any increase in the adverse events. So there were no new side effects. And overall, the tolerability was quite acceptable.

The second presentation was about the second line treatment of EGFR receptor mutated patients, where we have seen an update on the combination of Ivonescimab and chemotherapy compared to chemotherapy alone in the second line treatment for EGFR receptor mutated patients. In the HARMONi trial, we already know that there was also improvement of progression free survival. We have seen an update confirming the significant prolongation of progression free survival for the combination, but now we also have seen overall survival data. It has not been a significant improvement of overall survival, but there's a very strong trend in overall survival favoring the combination of Ivonescimab and chemotherapy. Again, when we look on the safety adverse events, in particular, when we look on the adverse events of interest in immunotherapy related and the angiogenesis related address events, there was no new Information.

The third very important abstract was on another oncogenic entity, ROS1 alterated non small lung cancer patients. And there we have seen the update on the data of a new compound Zidesamtinib (in ARROS-1 trial) . And we have seen quite remarkable clinical efficacy data in pretreated patients in terms of response, but also in terms of progression free survival, also in patients who had already received advanced TKI like repotrectinib. And together with a very favorable safety profile, this is clearly a drug of high interest for the future development.

肿瘤瞭望：您在2025 WCLC分享了IMforte研究结果（摘要MA11.04）。相比传统一线免疫维持方案，芦比替定（Lurbinectedin）联合阿替利珠单抗作为广泛期小细胞肺癌（ES-SCLC）一线维持治在机制上或临床疗效上有何优势？相关安全性结果对该方案适用人群的选择有何启示？

Martin Reck：总体而言，IMforte研究是全球首个在ES-SCLC一线维持治疗中显示出PFS和OS双主要终点均显著改善的III期研究。IMforte研究对象为已接受4个疗程化疗+免疫诱导治疗（方案：阿替利珠单抗+卡铂+依托泊苷）后未出现疾病进展的ES-SCLC患者。患者1:1随机分组接受芦比替定+阿替利珠单抗或单用阿替利珠单抗维持治疗。与阿替利珠单抗标准维持治疗方案相比，芦比替定+阿替利珠单抗治疗的疗效显著提高。我们观察到，联合治疗在主要终点（PFS和OS）方面均有显著改善。如前所述，这是首个在维持治疗中显示这种疗效改善的试验。

我认为对于ES-SCLC患者来说，这是一个好消息，因为在使用免疫检查点抑制剂进行维持治疗期间存在疾病进展的风险，只有极少数ES-SCLC患者能够长期生存。因此，任何能够提高疾病长期稳定患者比例的治疗方案都值得欢迎。在2025 WCLC上，IMforte研究也发布了安全性数据的更新，联合治疗方案的毒性的确更高，主要是血液学毒性和全身性症状（constitutional toxicity），但这些不良事件大多为一级和二级。而且大多数不良事件发生在治疗的前9-12周。总体而言，我们在这项更新的分析中没有发现任何新的副作用。维持治疗期间也没有发现任何累积毒性的迹象。所以我认为这对小细胞肺癌患者来说是一个真正的新治疗机会。

Martin Reck: IMforte was the first trial showing the efficacy of the approach of maintenance treatment in patients with advanced small lung cancer. The patients received four cycles of chemo-immunotherapy, and then they were randomized to receive the combination of lurbinectedin and atezolizumab or standard atezolizumab maintenance treatment. And we have seen a significant improvement in both co primary endpoints progression free survival and overall survival. And as mentioned before, this has been the first trial showing this efficacy in the maintenance setting. I think for patients with small cell lung cancer, this is a good story because there is the risk of progression during the maintenance treatment with the checkpoint inhibitor. We know that only very few patients can survive for a long time. So any chance to enhance the fraction of patients with a long term stabilization of the disease is highly welcome. And here at WCLC we have seen an update on the safety data. It's true. We do see a higher frequency of AE in the combination arm, mainly haematological toxicity and constitutional toxicity. But the majority of these adverse events were grade one and two. And the majority of these adverse events happened during the first 9 to 12 weeks of treatment. Overall, we do not see any new side effect with this updated analysis. We do not have any sign of a cumulative toxicity over the period of the maintenance treatment. I think this is a real new chance for our patients with small cell lung cancer.

肿瘤瞭望：在ES-SCLC领域，能否通过生物标志物实现更精准的患者分层，从而为患者提供更个性化的治疗？

Martin Reck：开发用于指导晚期小细胞肺癌患者的生物标志物是一个非常困难的历程。我们研究了PD-L1表达、肿瘤突变负荷（TMB）等常规标志物，但未发现其与疗效有任何关联。我们也发现了一些基因特征区分的亚型，它们可能与免疫疗法的疗效存在一定关联。这些生物标志物的问题在于，它们同时也是非常强的预后标志物，很难区分其预后价值和预测性价值。话虽如此，我认为生物标志物是正在进行的研究方向。我们距离为小细胞肺癌患者量身定制特定的治疗方案还有很长的路要走，我们必须尽早最大限度地为患者提高治疗机会。

Martin Reck: Development of Biomarker for guiding patients with advanced small Lung cancer is a very difficult story. We have looked on conventional markers like PD-L1 expression, tumor mutation burden and others, and we didn't find any correlation to the efficacy. We also identified some genetically determined subtype, which probably have some correlation to the efficacy of immunotherapy. The problem of these markers is the observation that they are also very strong prognostic markers. It's very difficult to differentiate the prognostic from the predictive quality. Having said this, I think this is ongoing research. We are a little bit faraway from customizing the patient for a certain treatment in small cell lung cancer. We really have to try to maximize the intensity of our treatment opportunities as early as possible.

肿瘤瞭望：请您谈一谈ES-SCLC研究方向，如何进一步改进临床实践？

Martin Reck：小细胞肺癌治疗的研究已经获得了重要的数据（例如IMforte研究），但这仅仅是个开始。现有免疫治疗选择有阿替利珠单抗，而新型免疫疗法正在出现，随机试验（DeLLphi-304）证明Tarlatamab单药对比标准化疗可显著改善含铂方案经治ES-SCLC患者的OS，这是小细胞肺癌治疗领域的一类新疗法，其应用显然也将向更早期患者推进，用于一线维持治疗，甚至一线治疗。这一领域还有很多其他值得关注的药物，例如ADCs正在被广泛研究,双特异性抗体也有研究进展，PD-(L)1/VEGF双特异性抗体现已被引入小细胞肺癌的一线治疗。因此，未来将会有大量关于小细胞肺癌的新数据涌现。

Martin Reck: When we look on the future of small cell lung cancer, we have seen now the IMforte data, but this is just the beginning. So we have a new class of immunotherapies coming up, we have atezolizumab, as we have seen the randomized trial of tarlatamab verus chemotherapy in pretreated patients showing a significant benefit in overall survival. This is a new class coming into the treatment field of small cell lung cancer, and obviously will come also to earlier stages, maintenance stage or even first line treatment. We have other agents of interest like the ADCs, which are currently in broad investigation. We have bispecific. So we have the PD-1 and VEGF antibodies, which are now also have been introduced into the first line treatment of small cell lung cancer. There is a lot of new data coming up in the future of small cell lung cancer.

来源：肿瘤瞭望