Osimertinib mesylate

2026年3月25日至28日，欧洲肺癌大会（ELCC）在丹麦哥本哈根盛大召开。作为胸部肿瘤学领域的国际顶级学术盛会，本届ELCC汇聚了全球肺癌诊疗的前沿科研成果与临床智慧，多项重磅研究相继揭晓，为肺癌精准治疗提供了新的循证依据与发展方向。近年来，可切除非小细胞肺癌（NSCLC）的围手术期治疗正从“单一手术”迈向“综合治疗”。随着CheckMate-816、KEYNOTE-671等III期研究的公布，免疫治疗已成为驱动基因阴性Ⅱ~Ⅲ期NSCLC的新标准。然而，新辅助与围手术期模式如何选择、Ⅱ期患者是否需要强化治疗、病理完全缓解（pCR）后能否省略辅助免疫等关键问题，仍是本次大会讨论的热点。 对此，《肿瘤瞭望》特邀法国巴黎居里研究所Nicolas Girard教授接受专访，围绕围手术期免疫治疗的个体化决策、pCR与ctDNA的指导价值及未来精准治疗方向展开探讨。特此整理，以飨读者。 《肿瘤瞭望》 近年来，CheckMate-816确立了新辅助免疫治疗在可切除NSCLC中的地位，而KEYNOTE-671、AEGEAN等围手术期研究进一步拓展了治疗边界。本次ELCC大会特设专场就两种策略的优劣展开讨论。首先，请您结合临床实践经验及相关研究进展，谈谈您如何看待“新辅助”与“围手术期”这两种策略在当前可切除NSCLC临床实践中的定位？在缺乏头对头比较的情况下，我们应如何为患者选择最优路径？ Prof. Nicolas Girard   我认为新辅助治疗是患者全程管理中的关键第一步。对于大多数可切除的驱动基因阴性Ⅱ~Ⅲ期非小细胞肺癌（NSCLC）患者，目前的标准方案是接受3~4个周期的新辅助化疗联合免疫治疗，随后进行手术。 至于后续是否需要辅助治疗，基于CheckMate-816研究的长期随访数据，我们看到：在单纯新辅助策略（仅术前治疗）与围手术期策略（术前+术后）之间，患者的长期无事件生存期（EFS）和总生存期（OS）实际上非常接近。这意味着，并非所有患者都需要术后辅助免疫治疗。问题的核心在于个体化决策——如何识别哪些患者能够从新辅助治疗后的辅助治疗中真正获益。 从现有数据来看，目前最重要的预后预测因素是病理完全缓解（pCR）。那些达到pCR的患者治愈机会极高，术后复发和死亡风险非常低。因此，这部分患者很可能不需要接受新辅助后的辅助免疫治疗。 然而，对于未达到pCR的患者，情况要复杂得多。其中一部分患者即使未达pCR，仍然可以被治愈，无论是否追加辅助治疗。跨试验比较提示，围手术期免疫治疗可能为这部分患者带来一定获益，但我们仍需要更精准的预测标志物。正如本次会议中所讨论的，ctDNA（循环肿瘤DNA）动态监测可能是一个有价值的方向。值得关注的是，这些患者的复发大多发生在局部区域，即肺或淋巴结。 Prof. Nicolas Girard: I think that neoadjuvant is a key first step in the management of patients. Most of the patients should receive chemo-immunotherapy as neoadjuvant treatment, three or four cycles, then moving to surgery. And then there is a question of what to do in the adjuvant treatment. Based on the CheckMate-816 study, there is no need for adjuvant treatment. We have long-term EFS, long-term OS figures that are actually similar in a pure neoadjuvant strategy versus a perioperative strategy. But at the end, it's a matter of individual patient decision-making and how to know who are the patients benefiting from adjuvant post-neoadjuvant. So the perioperative strategy versus a pure neoadjuvant treatment: based on the data, the most significant prognostic factor now is pathological complete response. So in those patients who achieve a pCR, the chance of cure is really high. There are very few patients showing disease recurrence, very few patients dying from evolution of the disease. So those patients achieving pathological complete response probably do not need adjuvant post-neoadjuvant. For the other patients, it is less clear because there are still some of these patients not achieving a pCR that are cured, whatever you do. There is probably a trend when doing cross-trial comparison towards the benefit of immunotherapy in the perioperative setting for those patients. But we need more predictors, and maybe as discussed during the session, ctDNA may be of interest. Predictors for recurrence are of interest. Interestingly, most of the recurrences in those patients actually occur locoregionally, the lung or in the lymph nodes. 《肿瘤瞭望》 多项III期研究亚组分析显示，Ⅱ期NSCLC患者从新辅助免疫治疗中的获益似乎不如Ⅲ期显著。在本次大会的“Educational session: Perioperative treatments for early lung cancer”中，也多次强调“精准分层”的重要性。您认为对于Ⅱ期患者，是否应更谨慎地推荐新辅助免疫治疗？ Prof. Nicolas Girard   我对此并不完全同意。因为不同分期患者在接受新辅助化疗联合免疫治疗后，其疗效和实际生存数据其实是相似的。之所以在临床试验中看到Ⅱ期患者的风险比（HR）低于Ⅲ期患者，主要是因为对照组的表现不同：Ⅰ~Ⅱ期患者即使只接受新辅助化疗，预后也相对较好；而Ⅲ期患者单纯化疗的效果明显更差，因此免疫联合化疗带来的相对获益更大。 但我们要看到，Ⅱ期患者同样存在复发风险。在接受新辅助化疗联合免疫治疗后，他们的pCR率可以达到15%~20%，远高于不接受新辅助治疗（0%）或仅接受新辅助化疗（约2%）的患者。鉴于pCR与长期治愈之间的高度相关性，我认为Ⅱ期患者同样应该接受新辅助化疗联合免疫治疗，尤其是那些存在淋巴结转移、肿瘤负荷较大或PD-L1高表达的高危患者。 Prof. Nicolas Girard: I kind of don't agree with that, because the efficacy and the actual survival figures for patients depending on stage are actually similar in patients receiving neoadjuvant chemo-immunotherapy. It's just a matter of the control arm. Obviously, patients with earlier stage disease, stage I, stage II, the control arm with chemotherapy is already doing quite well, but it's not the case in stage III. So this is why the hazard ratio is lower in stage III versus stage I and II. But those patients with stage II disease, we know may present with disease recurrence. With chemotherapy plus immunotherapy neoadjuvant, we see pathological complete response rates around between 15% and 20%, which is higher than 0% if you do not do neoadjuvant, and higher than that of chemotherapy, which is still 2% in this group of patients. So given the fact that we have this high correlation between pCR and long-term cure, I believe that those patients should receive chemoimmunotherapy as well. 《肿瘤瞭望》 KEYNOTE-671和CheckMate-77T等研究显示，围手术期免疫治疗在未达到pCR的患者中仍能带来EFS获益。在本次大会中，我们也看到了关于pCR与非pCR患者长期随访的新数据。您如何评估术后辅助免疫治疗在“已接受新辅助治疗”患者中的叠加价值？是否所有未达pCR的患者都应继续接受辅助免疫？ Prof. Nicolas Girard   我认为，对于达到pCR的患者，大概率不需要辅助治疗。而对于未达到pCR的患者，目前尚无定论。这部分患者存在高度异质性：残留肿瘤细胞10%与80%显然不是同一回事；ctDNA阳性与阴性也可能决定不同的复发风险；此外，患者的初始分期也可能影响决策。 目前，有一些正在进行的随机对照试验试图回答“未达pCR患者是否需要辅助免疫治疗”这一问题。在缺乏明确证据的情况下，我们只能基于现有手段进行务实的临床决策。现阶段，许多临床医生会选择给这些患者继续使用辅助免疫治疗，因为这是我们手中可用的工具。但未来，我们迫切需要更好的生物标志物来指导个体化治疗。 Prof. Nicolas Girard: I think this is reasonable to say that patients with pCR probably need no adjuvant. Patients without pCR, we don't know what to do. There is a heterogeneity in those patients. Maybe adjuvant IO is providing a benefit, maybe not. There are some ongoing randomized trials to address this question. We probably need some additional markers because it's also a continuum: 10% residual viable tumor cells versus 80% is probably not the same. ctDNA-positive versus ctDNA-negative is probably not the same. Maybe stage also impacts the decision-making. As of today, we do not know that much. And what we have is immunotherapy. So pragmatic clinical decision-making, as of today, is to give preoperative immunotherapy to those patients. 《肿瘤瞭望》 尽管ADAURA和ALINA研究确立了EGFR/ALK阳性患者术后辅助靶向治疗的地位，但免疫治疗在该人群中的应用仍存在诸多争议。您如何看待在驱动基因阳性可切除NSCLC中尝试免疫治疗的风险与获益？ Prof. Nicolas Girard   对于驱动基因阳性（如EGFR突变、ALK融合）NSCLC患者，治疗策略完全不同。这类患者的核心是辅助靶向治疗。ADAURA研究和ALINA研究已经明确证明，奥希替尼和阿来替尼辅助治疗能够显著降低术后复发风险，尤其是脑转移风险。因此，术后辅助靶向治疗是标准路径，免疫治疗不仅无明确获益，还可能增加间质性肺炎等风险。 对于部分局部晚期（如Ⅲ期）的驱动基因阳性患者，新辅助靶向治疗（或化疗联合TKI）也有一定价值。NeoADAURA研究以及奥希替尼、阿美替尼的真实世界数据提示，新辅助靶向治疗可以实现肿瘤降期，提高手术切除率。因此，合理的策略是：先使用化疗联合TKI进行新辅助治疗，然后择期手术，术后继续辅助靶向治疗。总体而言，免疫治疗在驱动基因阳性可切除NSCLC中不推荐常规使用。 Prof. Nicolas Girard: In oncogene-driven tumors, it's a completely different strategy. It's adjuvant, mostly, and the role of adjuvant is preeminent in those patients because the risk of disease progression after surgery is high. And to me, the contribution of local treatment (surgery) in those patients is actually lower. It obviously depends on stage, but there is a more preeminent role of the systemic treatment to protect against systemic recurrence, which is quite frequent in those patients, especially in the brain. So to me, it's more like a matter of adjuvant, more like a matter of duration of driver treatment, and there are still open questions for that. In some patients with stage III disease, especially, we have the data from the NeoADAURA trial. There is some value in giving the TKI or chemo plus the TKI neoadjuvant. And we have data with osimertinib as well as aumolertinib suggesting that we can achieve a higher downstaging, facilitating surgery. So if we believe that there is a contribution of surgery in those patients (which is the case), I feel that it's reasonable and pragmatic to say: let's start with chemo plus TKI, then move to surgery at a certain point. But there will be a need for the adjuvant component for the treatment of these patients. 《肿瘤瞭望》 随着围手术期免疫治疗地位的不断巩固，如何优化治疗强度、缩短疗程、减少毒性成为新的焦点。本次大会围绕“放疗与免疫协同”“T细胞衔接器”等新型策略的讨论，预示着围手术期治疗正迈向精准化与多元化。展望未来，您认为该领域的主要突破点可能出现在哪些方向？ Prof. Nicolas Girard   未来的核心方向是实现更精准的个体化决策，尤其是在治疗强度上需要“升阶梯”与“降阶梯”的平衡。我们面临的现实是：在未达到pCR的患者中，仍然有一半会出现疾病复发并最终死于肺癌进展。因此，这部分高危患者需要更强化的治疗。 如何升阶梯？可能是联合ADC药物、双特异性抗体，或是肿瘤疫苗。例如，基于患者肿瘤组织所表达的新抗原的个体化疫苗，正在早期临床试验中展现出潜力。当然，升阶梯并不适用于所有患者。对于已经达到pCR或ctDNA持续阴性的低风险人群，我们或许可以安全地减少甚至省略辅助治疗。总之，这个领域正在快速发展，我们期待为患者带来更多、更好的治疗选择。 Prof. Nicolas Girard: Better personalization of the decision making escalation probably because especially in patients without pCR we still see half of the patients showing disease recurrence and dying from the evolution of lung cancer. So escalation, but maybe not for all the patients. How to escalate? Is it ADC, bispecifics, vaccines? Probably something also that is there in clinical trials: personalized vaccines based on the antigens that are expressed in the tumor tissue of a given patient. So everything is moving quite quickly in this field, and hopefully we will have new opportunities for the patients. 专家简介 Nicolas Girard 教授 法国居里研究所肿瘤内科主任，胸部肿瘤科主任 萨克雷大学的呼吸医学教授 肺癌和罕见胸部恶性肿瘤专家 在同行评审的期刊上发表了300多篇论文 参与多项可切除、局部晚期和转移性非小细胞肺癌的里程碑式试验 （来源：《肿瘤瞭望》编辑部） 声 明 凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。