在2025年欧洲肺癌大会（ELCC）上，III期MARIPOSA研究的最终总生存（OS）数据引发广泛关注。本文通过法国国家科学研究中心里昂癌症研究中心Maurice Perol教授的深度解读，剖析MARIPOSA研究的临床意义，探讨联合治疗的适用人群及风险分层依据。

 

Dr.Perol：2025 ELCC大会发布的MARIPOSA试验的总生存分析结果显示，埃万妥单抗联合兰泽替尼的中位总生存期较奥希替尼显著延长（未达到vs.36.7个月），风险比为0.75。这是自FLAURA研究以来首个证明EGFR突变晚期非小细胞肺癌患者总生存期可能被进一步改善的研究，无疑是此类患者管理方面的重要进展。

 

 

然而，这一获益的代价是毒性显著增加，尤其是皮肤毒性、输注相关反应和静脉血栓栓塞风险。这些毒性需要积极管理以降低高级别毒性的发生率。皮肤毒性和头皮毒性对患者和临床医生而言都是棘手的问题。

 

Dr.Perol:For the MARIPOSA trial，the overall survival analysis was presented at ELCC，showing that the combination of amivantamab and lazertinib was able to significantly improve median overall survival from approximately three years for osimertinib，to not reached for the amivantamab/lazertinib combination.The hazard ratio was 0.75.This is the first study to demonstrate that it is possible to improve overall survival for patients with EGFR mutation advanced non-small cell lung cancer since the FLAURA trial.So this is a great advance of course for the management of these patients.

 

However，this was at the cost of a significant amount of additional toxicity，especially the dermatological toxicity，the infusion-related reactions and the risk of venous thromboembolism at the beginning of the treatment.All these toxicities need proactive management in order to reduce the rate of high-grade toxicity.Clearly，the skin and scalp toxicity remains an issue difficult to manage for patients，and also for the oncologists.

 

Dr.Perol：目前我们有两种强化一线治疗选择：MARIPOSA研究中的埃万妥单抗/兰泽替尼联合方案，以及FLAURA2研究中的化疗联合奥希替尼方案。二者均可能改善总生存期（OS）：2025 ELCC发布的MARIPOSA研究OS数据已证实这一点，FLAURA2的总生存分析也可能显示相似幅度的获益。这些联合方案改善患者生存的机制并非通过提高总体缓解率（与奥希替尼单药相近），而是通过延长缓解持续时间、预防或延缓获得性耐药的发生。

 

PFS的获益程度对于OS转化很重要。因此，在一线治疗中，最好提供最佳治疗方案。但需注意，并非所有患者都适合联合治疗（如体弱或老年患者），对于希望维持更好生活质量的患者（奥希替尼单药治疗可能比联合治疗更容易实现这一点），奥希替尼单药治疗仍然是一个经过验证的选择。

 

关于选择联合方案还是奥希替尼单药，我们倾向于早期进展风险高的患者采用联合方案（而不是奥希替尼单药）。早期疾病进展风险高的患者特征包括：高肿瘤负荷高；存在中枢神经系统（CNS）转移；基线ctDNA检测出的基因组特征提示高风险（可能是TP53突变，也可能是EGFR外显子21突变，而非外显子19缺失）。此外，临床医生需评估患者的合并症及患者对化疗、埃万妥单抗/兰泽替尼联合治疗的耐受性。综合这些因素后，对具有高风险基因组特征的患者选择更强效的联合方案。

 

Dr.Perol:Well，we have now two possible intensified first-line treatment options with the amivantamab/lazertinib combination from the MARIPOSA study，and the combination of chemotherapy and osimertinib with the FLAURA2 regimen.Both will probably lead to an improvement in overall survival.This is demonstrated for the MARIPOSA regimen，and the overall survival in the analysis of FLAURA2 will likely demonstrate the same magnitude of benefit.These combinations worked not by improving the overall response rates(which are very similar to that of osimertinib monotherapy)，but works by extending the duration of response by preventing or delaying the emergence of acquired resistance.

 

The magnitude of benefit in terms of PFS is important enough to translate over to overall survival.So，it is probably better to give the best treatment option in first-line;however，as all patients are not eligible for the combination(frail patients，elderly patients)and for patients who wish to preserve their quality of life(which is probably easier to do with osimertinib monotherapy rather than with a treatment combination)，osimertinib monotherapy still remains a validated option.

 

We are inclined to reserve treatment combinations for the patients with high risk of early disease progression over osimertinib monotherapy.Those patients with high risk for early disease progression are patients with a high tumor burden，with CNS metastases，with a genomic profile detectable by ctDNA at baseline，probably the TP53 mutation，probably also the exon 21 mutation rather than the exon 19 deletion，we also need to consider a patient’s comorbidities and their ability to tolerate chemotherapy or the amivantamab/lazertinib combination.All of these factors have to be taken into account before selecting the best treatment option.For the patients with a high risk genomic profile，I would be tempted to give the combination treatment，which is more effective.

 

Dr.Perol：在2025 ELCC目前已发布的日程中，我比较关注EGFR突变领域的重要进展，因为该领域发布了最重要的进展；此外，在KRAS G12C突变NSCLC患者中开展的西妥昔单抗联合KRAS G12C抑制剂的研究也很有趣（KROCUS研究，摘要LBA1）。我认为本次会议报道的MARIPOSA试验无疑是能改变临床实践的研究，实现了具有统计学意义和临床意义的总生存期显著改善。

 

Dr.Perol:As I have not seen all of the presentations as we are still at the beginning of the Conference，I would probably select the presentations about EGFR mutations，because in this field，we have the most important advances.We also have some interesting presentations for the KRAS-mutated patients with combinations of cetuximab and KRAS inhibitors.We also have some interesting data in this field.But I think for ELCC 2025，EGFR-mutated patients are the most important setting in terms of advances.I think the MARIPOSA trial，that is clearly a practice-changing study，because there is a significant and clinically relevant improvement in overall survival.Clearly for me at least，this is the most practice-changing study at the Conference.

 

《肿瘤瞭望》在ELCC现场报道