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[WCLC2016]对话WCLC之巅——“NSCLC靶向治疗与免疫治疗进展”国内外顶尖专家圆桌会会议纪要

作者:  陈颖   日期:2016/12/23 16:55:06  浏览量:33047

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编者按:在第17届世界肺癌大会(WCLC)上,为进一步促进中国医生与国际顶级肺癌大咖的交流和互动,我们特别邀请同济大学附属上海市肺科医院周彩存教授、奥地利维也纳Otto Wagner医院Maximilian Hochmair教授出席《肿瘤瞭望》倾力打造的“对话WCLC之巅——‘非小细胞肺癌(NSCLC)靶向治疗与免疫治疗进展’圆桌会”,与16名中国医生进行面对面的交流、碰撞思想火花,评论本届会议热点亮点,探讨NSCLC靶向治疗的一线选择、罕见基因突变治疗、耐药后治疗、免疫治疗抉择等,共绘NSCLC治疗蓝图。

  一、WCLC2016:最深刻的数据

 

  周彩存教授:在本届WCLC上,您觉得印象最深刻的数据有哪些?

  Prof. Caicun Zhou: What data have impressed you most from this meeting?

 

  Maximilian Hochmair教授:①从临床数据看,我们现在正改变TNM分期,而这是非常重要的。我认为,治疗寡转移患者是非常重要的,正如我们以往认为的,但不同的是,现在我们可以对这类患者进行TNM分期了。②会上公布了ASCEND-4研究数据,我认为,色瑞替尼(ceritinib)作为一线治疗是非常有用的药物。令我震惊的是,那些没有脑转移的患者有超过24~25个月的无进展生存期(PFS)。我是该项研究的共同作者,研究中我们有两名来自亚洲的患者,他们在30个月后仍然在接受药物治疗。所以,这是一个潜在有效的药物。不良反应较艾乐替尼(alectinib)多一点,但是,我认为它还是一个好药。③会上公布了AURA3研究比较osimertinib与化疗在二线治疗中应用的最新结果。④我是brigatinib治疗ALK突变患者试验的共同作者,颅内缓解的效果令人震惊,我们在此次WCLC会上展示了这些结果。⑤此外,免疫治疗的数据也是非常令人感兴趣的。

  Prof. Maximilian Hochmair: From the clinical data, it is important that we are changing the TNM classification now. I think it is very important to be treating oligometastatic patients like we used to but now we have the TNM classification for those patients.They presented the ASCEND-4 data, and I think ceritinib as first-line treatment is a very useful drug. What I was very amazed by was that those patients who had no brain metastasis had more than 24-25 months of PFS.I was co-author of the study and we had two patients from Asia in the study, and they are still receiving the drug after more than 30 months. So this is a potentially useful drug. Side effects are a little more compared to alectinib, but I think it is a good drug.There is the AURA3 trial, comparing osimertinib versus chemotherapy in the second-line. I am co-author of the brigatinib trial for ALK-mutated patients, and the intracranial remissions have been amazing and we are presenting those results at WCLC.The immune therapy data will also be interesting.

 

  二、一线EGFR-TKI的选择

 

  周彩存教授:您所在国家(奥地利),现有三种EGFR-TKI可供选择(吉非替尼、厄洛替尼和阿法替尼),那么,您是如何选择每种药物的适用患者?

  Prof. Caicun Zhou: Now, in your country, you have three EGFR tyrosine kinase inhibitors, which have first-line indications for EGFR-mutant lung cancer - gefitinib, erlotinib and afatinib. How do you select the patients for each compound?

 

  Maximilian Hochmair教授:我认为,阿法替尼(afatinib)是目前所有基因突变类型患者的一个标准用药,在EGFR基因外显子19缺失(Del 19)及罕见突变患者中的疗效尤为突出。LUX-Lung 7研究发现,相比于吉非替尼,阿法替尼在PFS、延长至治疗失败时间(TTF)和增加缓解率方面有一定优势;在患者存活率方面,没有显著差异。

  Prof. Maximilian Hochmair: I think afatinib is now standard for all mutated patients. So for rare mutations and deletion 19, I think, the situation is very clear. With LUX-Lung 7, we have an advantage with PFS,extended time to treatment failure and increased response rate when compared to gefitinib. In terms of survival, there is no real difference.

 

  周彩存教授:对于EGFR L858R突变的患者,您倾向于选择阿法替尼还是厄洛替尼?

  Prof. Caicun Zhou:What about patients with exon 21 L858R point mutation? Do you prefer afatinib or erlotinib in your country?

 

  Maximilian Hochmair教授:随着更多试验的开展,我一直期待看到这些药物的对比数据。目前,我们进行了一项比较阿法替尼与吉非替尼疗效的研究,结果阿法替尼在其中两个研究终点的结果优于吉非替尼;对于其他终点,二者相似。基于这项比较性研究,我会给予EGFR L858R阳性患者阿法替尼治疗。在中国,您是如何处理这些患者的?

  Prof. Maximilian Hochmair:With these trials, I was always waiting for a comparison of these drugs. We have now a comparison, ands for two endpoints, afatinib was better compared to gefitinib. For the other end point, they were similar. Now I have that comparison, I go for afatinib in these patients.How do you approach these patients in China?

 

  周彩存教授:在中国,对于EGFR突变肺癌患者,我们可获得三种EGFR-TKI,吉非替尼、厄洛替尼和埃克替尼。阿法替尼尚未获批使用,预计于2017年初上市。届时,面对众多EGFR-TKI,我们可能更难进行选择,这也正是我问您这些问题的原因。

  Prof. Caicun Zhou: In China, we have three compounds available for EGFR-mutated lung cancer – gefitinib, erlotinib and icotinib. Afatinib has not been approved yet; maybe not until the beginning of next year. So we have an even more complicated situation in selecting TKIs. That is why I asked you these questions.

 

  三、HER2阳性患者治疗

 

  参会医生:存在EGFR突变的患者,可能同时存在HER2突变或扩增。那么,阿法替尼对HER2阳性患者是否有效?

  Question: I have a question about afatinib in the EGFR mutation setting, where there is HER2 mutation or amplification. What is the role of afatinib in patients who are HER2-positive?

 

  Maximilian Hochmair教授:现在关于HER2的研究非常少,似乎仅有基于5例患者的数据被发表。我们在临床实践中,会评估患者是否存在HER2突变,给予阳性患者阿法替尼治疗。截至目前,我们收集了3例HER2阳性患者,他们均在治疗早期获得了很好的应答。我认为,阿法替尼是一种非常有效的药物,对HER2阳性患者有潜在的作用,所以评估HER2情况是有必要的。

 

  随着下一代测序(NGS)技术的发展,我们将鉴别出更多HER2阳性患者。未来的难点可能会在靶向治疗与免疫治疗间的选择,即对于PD-L1表达非常高或不高的HER2患者,靶向治疗是否仍能发挥作用。目前,我们正使用阿法替尼治疗这类患者,但是3例患者的数据显然太少,不足以提供循证医学证据。

  Prof. Maximilian Hochmair: There is very little data about HER2. I think data on only 5 patients has been published. In our clinic, we measure HER2 and we treat patients with afatinib in this situation. We have three patients at the moment. They show a clear response, but it is very early. But I think it is a useful drug and it is necessary to measure HER2 and there is the potential to treat them.

 

  With next-generation sequencing, we will identify more patients in this situation. The differentiation will be whether it matters if the PD-L1 expression is very high or not and should be go for targeted therapy or PD-L1 inhibition. At the moment, we are using afatinib in these patients, but three patients is not a lot.

 

  周彩存教授:HER2突变的发生率不是非常高(1%~3%),所以如果我们想做大型临床试验,几乎是不可能的。或许我们可以做单臂研究,得到一个明确的获益,一个可以接受的应答率,以及可接受的PFS。

  Prof. Caicun Zhou: The incidence of HER2 mutation is not very high, about 1-3%. If we want to do big trials, it is almost impossible. Maybe we can do single arm studies. We can get a clear-cut benefit, an acceptable response rate and acceptable progression-free survival.

 

  Maximilian Hochmair教授:从临床试验看,HER2可能是吉非替尼或厄洛替尼治疗患者的耐药性突变。我认为,目前我们正使用阿法替尼作为所有患者的一线治疗,所以再活检发现HER2突变的情况将更为罕见。

  Prof. Maximilian Hochmair: When you use gefitinib or erlotinib, HER2 can be a resistant mutation and that has been shown in trials. I think now that we are using afatinib as first-line treatment for all patients, a rebiopsy will find HER2 mutations are more rare.

 

  四、EGFR-TKI获得性耐药治疗

 

  周彩存教授:现在,我们做了很多对TKI产生获得性耐药的患者的再活检。也许,您也做了很多再活检。那么,您在接受厄洛替尼、吉非替尼和阿法替尼治疗失败的EGFR突变患者中,发现了任何不同吗?这是一个非常重要的、需要我们去回答的问题。因为,如果一线阿法替尼有更少的EGFR获得性突变,那么患者将有更少的可能需要再接受osimertinib治疗。

  Prof. Caicun Zhou: Now we do a lot of rebiopsies of acquired resistance to TKIs. Perhaps you do a lot rebiopsies also. Do you find any differences in the EGFR mutations seen in the failure of erlotinib, gefitinib and afatinib? This is a very important question we need to answer. If first-line afatinib induces less EGFR mutation, the patients have less chance to be treated with osimertinib.

 

  Maximilian Hochmair教授:这确是一个非常重要的问题。我们有超过200例接受阿法替尼治疗的EGFR突变患者,正整理相关数据以期发表。我们的T790M突变发生率约为60%,未观察到这类药物在T790M突变上的显著差异。我一直对由osimertinib、rociletinib和mereletinib带来的耐药性突变感兴趣,三者之间可能存在一定的差异,但遗憾的是后两个T790M阻断剂未有进一步的进展。对于rociletinib,C797S突变根本没有出现。或许不同EGFR-TKI产生的耐药突变会有不同,但在我们患者中尚未发现差异。据我所知,关于这个问题的亚洲数据是来自韩国的一个30~40例患者的小队列研究,T790M突变发生率为50%。

  Prof. Maximilian Hochmair: We had more than 200 EGFR-mutated patients getting afatinib, and was collecting data to be published, and it is a very important question. We have about 60% incidence of T790M, and we did not find a real difference between the drugs..I would have been interested in the resistance mutations that developed with osimertinib, rociletinib and mereletinib. There could be a difference, but unfortunately the latter two T790M blockers are not further developed. For rociletinib, the C797S mutation didn’t show up at all. Perhaps there would have been a difference but in our patients, we didn’t find it. The only publication regarding this in Asia is from Korea, I think, and it showed 50% incidence of T790M mutation from a small cohort of 30-40 patients

 

  周彩存教授:所以,在EGFR T790M突变方面,一代TKI与二代TKI实际上没有显示出差异。

  Prof. Caicun Zhou: So the first and second generation actually show no differences in the EGFR T790M mutation.

 

  参会医生:对于L718Q突变患者,您有什么建议吗?

  Question: I had a patient with a L718Q mutation. I gave this patient afatinib. What would you advice be for this patient?

 

  Maximilian Hochmair教授:我们可以回顾LUX-Lung 2、LUX-Lung 3和LUX-Lung 6研究,这其中包括一些罕见突变。在这些患者中,我们看到的与临床实践中见到的一致,罕见突变患者接受阿法替尼的疗效与存在或不存在Del 19突变的患者一样,都获得了治疗应答。对于你说的L718Q突变,我有3例患者存在这种突变,对脑转移也有明确的应答。两个月前,我发表了一个案例,阿法替尼治疗L718Q突变患者是有效的。我认为,在罕见突变中,与厄洛替尼或吉非替尼相比,阿法替尼的疗效是毋庸置疑的。

  Prof. Maximilian Hochmair: So we have to look at LUX-Lung 2, LUX-Lung 3 and LUX-Lung 6, which included rare mutations. What we saw in these patients as well as in our clinic, was that rare mutations receiving afatinib is the same with deletion 19 or without. They did all response.For the L718Q mutation you have, I have three patients at the moment with that mutation, with a clear response also in the brain. I published a case two months ago with your mutation and it responded. I think in rare mutations, for afatinib there is no discussion compared to erlotinib or gefitinib.

 

  周彩存教授:我们已经看到一项单臂Ⅱ期试验(BELIEF研究),联合贝伐珠单抗与厄洛替尼治疗。在EGFR T790M突变患者中,尤其是PFS方面,有延长。您有一些关于贝伐珠单抗联合阿法替尼治疗的临床经验吗?

  Prof. Caicun Zhou: We have seen the single arm phase II trial, the BELIEF study, with bevacizumab and erlotinib. There was an increase in progression-free survival especially in patients with EGFR T790M mutations. Do you have any experience of bevacizumab and afatinib in practice?

 

  Maximilian Hochmair教授:现在的问题是保险机构不支付这种状态下的贝伐珠单抗治疗。相比于厄洛替尼+贝伐珠单抗治疗,阿法替尼单药治疗的数据几乎一致。我更倾向于选择阿法替尼+贝伐珠单抗治疗。在奥地利,用法是一个标签,但在没有明确的优势时,医院可以说不。

  Prof. Maximilian?Hochmair: The problem is the insurance companies are not paying for bevacizumab in this situation. The data is nearly the same for afatinib alone compared to erlotinib plus bevacizumab. I would prefer a trial with afatinib plus Avastin. In Austria, usage is on-label, but the hospital says no, as there is no clear advantage.

 

  五、EGFR-TKI获得性耐药基因检测

 

  参会医生:我们知道阿法替尼对一代EGFR-TKI(如吉非替尼和厄洛替尼)的获得性耐药治疗有一定疗效。很多专家都相信阿法替尼是有效的,因为它是一个泛HER TKI。本届会议上,来自美国的专家展示了他们在第一代EGFR-TKI耐药患者中进行的基因组学分析。他们发现,一个体细胞突变启动了HER2突变,而这一突变不是传统的HER2突变(外显子20插入)。有病例报道显示,阿法替尼对这类体细胞突变也有作用。我们知道,HER2过表达也是EGFR-TKI获得性耐药的机制。

 

  如果患者对一代EGFR-TKI产生了获得性耐药,我们应该应用NGS技术来检测T790M突变吗?当对EGFR-TKI产生获得性耐药时,体细胞突变型HER2变异可能发生,那么在未来,我们是否应该仅对所有肺癌患者检测T790M突变?

  Question:We know afatinib shows some response in patients who get acquired resistance to the first generation of EGFR inhibitors such as gefitinib and erlotinib. Many experts believe afatinib is effective because it is a pan-HER tyrosine kinase inhibitor. Yesterday, some experts from United States presented their genomic analysis in patients who get the resistance to first generation EGFR TKIs. They found a somatic mutation initiates a HER2 mutation. This mutation is not the traditional HER2 exon 20 insertion. Some cases have reported that afatinib also works in this kind of somatic mutation. We know that the HER2 overexpression is also mechanism of acquired resistance in EGFR TKIs.

 

  My question is, if patients acquire resistance to first generation EGFR TKIs, should we perform next generation sequencing (NGS) to detect the T790M mutation? We also know that the HER2 somatic mutation could happen as acquired resistance to EGFR TKIs. In the future, should we just test all lung cancer patients for the T790M mutation?

 

  Maximilian Hochmair教授:非常好的问题。当你使用可逆的TKI,你应该尝试使用再活检以发现HER2突变。现在我正做的,就是使用阿法替尼,同时为那些患者做液体活检以尽早发现T790M。关于这个话题,我们在此次WCLC上有两篇摘要交流,甚至包括在低水平T790M突变液体活检测序方面的工作。

 

  如果可能的话,在进行再活检+液体活检时,我们也将做NGS。但目前我们仅能进行液体活检,没有其他选择,可能仅仅能检测T790M,因为在我们的临床中液体活检对HER2检测没有作用,我不知道是否中国有不同的经验。液体活检对ALK也没有作用。所以,目前我们仅仅应用液体活检技术检测T790M。当T790M为阴性时,我会应用NGS技术。您在上海告诉我,在中国,你们有更大的NGS样本量。目前在我们的临床中,NGS技术真是还不完美,因为它是非常昂贵的,很多患者支付不起,同时NGS在某些地方并不是真实的NGS。

  Prof. Maximilian Hochmair:Very good question. When you use the reversible TKI, you should try to use rebiopsy to find HER2. What we are doing at the moment is using just afatinib and doing a liquid biopsy for those patients to find early T790M. We have two publications at WCLC on this topic, and even in low level T790M mutation liquid biopsies sequencing works.

 

  We will do next generation sequencing (NGS), if it is possible when we do the rebiopsy plus liquid biopsy. When only a liquid biopsy is possible, we can only detect T790M, but nothing else at the moment. HER2 doesn’t work in liquid biopsy. I don’t know if China has a different experience, but HER2 is not working in our clinic. It also doesn’t work for ALK. So we just use it for T790M at the moment. When T790M is negative, we go for next generation sequencing. You have greater capacity for NGS in China, you told me, in Shanghai. It is really not perfect in our clinic at the moment because it is very expensive and not a lot of patients can afford it, and NGS in some places is not a real NGS.

 

   六、阿法替尼的不良反应管理

 

  参会医生:关于临床实践中,阿法替尼的毒性管理,您有什么建议吗?

  Questions: What are your recommendations for us for managing the toxicity of afatinib in clinical practice?

 

  Maximilian Hochmair教授:我们通常以40 mg开始给患者治疗。当没有副作用出现时,我会在1个月后增加剂量至50 mg;当有轻微不良反应时,维持剂量;当出现更多不良事件时,减少剂量至20 mg。根据我的经验,经过这些处理,阿法替尼的疗效并没有降低。在ASCO年会上,我们展示的2015年数据显示,更多的不良反应的出现,是伴随着高血药浓度的阿法替尼。当你降低剂量时,疗效保持不变,但是血药浓度降低。所以,当出现不良反应时,可以选择调低剂量来解决问题,但是,起始剂量被规定为40 mg。使用吉非替尼时,我们不能调整剂量,所以某些时候,这是阿法替尼的优势。

 

  最初,我们给予患者一线阿法替尼治疗时,出现了很多不良反应。在上海,我们讨论了这个问题。在用药初期,我们看到了更多的腹泻。当你不得不看到你的患者更频繁地出现腹泻时,情况就会变得复杂了。起初,我的一些同事告诉我,他们没有使用阿法替尼,因为他们的患者之前已经出现了腹泻。但从LUX-Lung 6研究看,我们发现,腹泻在亚洲患者中的发生率低于高加索人。

  Prof. Maximilian Hochmair: We normally start in patients with 30mg. When there are no side effects, I increase the dosage after one month. When there are minor side effects, I stay with the dosage. When there are some side effects, we reduce the dosage to 20mg. My experience is that there is no loss of efficacy with that approach.At ASCO, we presented 2015 data showing that the more side effects you have, the higher is the level of afatinib in the blood. When you reduce the dosage, the efficacy stays the same, but the blood level goes down. So when you have side effects, you can reduce the dosage and you can feel safe with this. But the starting dose is labeled as 30mg. With gefitinib, we cannot modify the dosage and this is a disadvantage sometimes.

 

  In the beginning, when we used afatinib for the first time, there were more side effects. We discussed this in Shanghai. We saw more diarrhea in the beginning. When you have to see your patients a little bit more often, it gets to be a little more complicated. In the beginning, some colleagues of mine told me that they didn’t use afatinib because their patients had diarrhea. From LUX-Lung 6, we saw that In Asian patients, the diarrhea is lower than in Caucasian patients.

 

  周彩存教授:阿法替尼,最初是在台湾使用,而台湾人和中国大陆人几乎没有太大的差异,我们说一样的语言,也经常一起交流治疗经验。所以在LUX-Lung 6研究中,患者在接受阿法替尼治疗的同时,我们给予腹泻的预防措施。

  Prof. Caicun Zhou: Afatinib was first used in Taiwan and because we share the same language, there is a lot of communication between Taiwan and Mainland China in terms of how to treat our patients. When afatinib was given to our patients in the trial, diarrhea prevention was also given.

 

 

  七、肺鳞癌治疗进展

 

  参会医生:本届WCLC上有很多关于肺腺癌的进展,那么您能给我们介绍一下肺鳞状细胞癌治疗的不同吗?

  Question: DrHochmair, at this meeting there has been a lot of information about adenocarcinoma. Could you tell us the difference with squamous?cell carcinoma therapy?

 

  Maximilian Hochmair教授:我认为,现在的不同是在PD-L1评估方面,在我们的临床中,对于有高PD-L1表达的患者(即>50%的PD-L1表达),会建议尽早接受pembrolizumab治疗。此外,我们也评估EGFR表达,应用necitumumab联合顺铂/吉西他滨治疗,这其中存在无或低PD-L1表达的患者。但是,我认为这个队列是太小了,没有很多正接受顺铂治疗的鳞状细胞癌患者。

 

  在二线设置中,我认为,当患者未尽早接受免疫治疗时,免疫治疗是最好的选择,nivolumab可独立于PD-L1表达进行选择。作为三线,阿法替尼是标准选择药物,多西他赛没有经常被使用,它的疗效与阿法替尼相似,所以我们正使用阿法替尼作为三线。四线将是多西他赛,如果患者仍然能够承受治疗的话。在三线或四线中,多西他赛剂量为三周60 mg/m2,或每周30 mg/m2

  Prof. Maximilian Hochmair:I think the difference now is that we measuring PD-L1 upfront, so in our clinic, for patients who have high expression of PD-L1 (meaning more than 50% PD-L1 expression), they receive pembrolizumab frontline. Plus, we are measuring EGFR expression, using necitumumab where there is no or low PD-L1 expression in combination with cisplatin/gemcitabine. But I think this cohort is very small. Not a lot of patients are receiving cisplatin for squamous?cell carcinoma.

 

  In the second-line setting, I think when patients do not receive immunotherapies frontline, then immunotherapy is the best choice with nivolumab independent of PD-L1 expression. And as third-line afatinib is the standard drug of choice. That would be our experience now. Docetaxel is not so often used because it is not as an aggressive drug. It has around the same efficacy as afatinib, so we are using afatinib in third-line. Fourth-line would be docetaxel if the patient is still able to receive something. In the third- or fourth-line, the docetaxel dose would be 60mg/m2 over three weeks, or we do 30 mg/m2 weekly.

 

  八、免疫治疗应用

 

  参会医生:当患者使用一代或二代EGFR/ALK-TKI后出现疾病进展时,我们使用三代药物。那么,对于EGFR或ALK敏感突变患者,是否需要进行免疫治疗或化疗?

  Questions: When patients use first generation EGFR/ALK TKIs and then progress, we use third generation drugs. When should we use immunotherapy after the use of first-line chemotherapy or second-line chemotherapy and when is it better to use chemotherapy for the EGFR or ALK sensitive mutation?

 

  Maximilian Hochmair教授:关于这个问题,我有一些临床实践经验。一线是阿法替尼;二线是osimertinib;对于PD-L1表达超过90%的患者,继续接受pembrolizumab作为三线治疗,没有化疗。我认为,在这种状态下我们需要检测PD-L1表达。我认为,常规的化疗是标准治疗,但评估PD-L1表达和T790M突变情况,可以帮助我们决策,继续靶向治疗、免疫治疗还是化疗。

  Prof. Maximilian Hochmair: I have an experience related to this in my clinic. Afatinib is the first-line. Second-line is osimertinib. Once the patient progressed, we found that PD-L1 expression was more than 90%. The patient went on to pembrolizumab as third-line treatment, and not chemotherapy. I think we need PD-L1 staining in this situation. Normally chemotherapy is standard of care. I think third-line if T790M is present. I think biopsy helps with decision for immunotherapy or chemotherapy.

 

  参会医生:EGFR敏感突变患者应用免疫治疗会出现严重的进展吗?

  Questions: Do EGFR-sensitive mutation patients progress badly with immunotherapy?

 

  Maximilian Hochmair教授:KEYNOTE-024研究中,并没有纳入较多EGFR突变患者。所以,我们不能说免疫治疗没有作用,但是当你可以找到一个靶点时,你应该选择靶向治疗。在后续治疗中,应进行用药前的评估。对于ALK突变患者,我们已经有5种抑制剂,如果没有更好的靶向药物可选择时,再考虑化疗还是免疫治疗,首选靶向治疗。

  Prof. Maximilian Hochmair: A lot of patients like this were not included in KEYNOTE-024, for example. EGFR-mutated patients were not included in the study. So we cannot say it does not work, but when you have a target, you should use targeted therapy. In later lines of therapy, I think you should test and decide on the best situation. In ALK-mutated patients, we have five different inhibitors already, which are all different. If you biopsy, you should decide when you have no targeted therapy any more,to use chemotherapy or immunotherapy. But targeted therapy comes first.

 

  参会医生:在KEYNOTE-024研究结果公布后,NCCN指南推荐:无EGFR或ALK敏感突变且PD-L1表达>50%的患者,应该接受pembrolizumab作为一线治疗。如果患者在接受EGFR或ALK抑制剂治疗后,疾病进展且PD-L1表达>50%,指南也推荐这类患者接受抗PD-1和抗PD-L1免疫治疗作为二线治疗。那么,对于一线或二线EGFR/ALK抑制剂治疗后进展的患者,您怎么看这第二个推荐?

  Question: After the release of the KEYNOTE-024 results, the NCCN Guidelines recommend that patients with no EGFR or ALK sensitizing aberrations and PD-L1 expression >50% should be treated with pembrolizumab as first-line therapy. If the patient is progressing after an EGFR or ALK inhibitor, and the patient also has PD-L1 more expressive than 50%, then they also are recommended to receive anti-PD-1 and anti-PD-L1 immunotherapy as second-line. What is your comment about the second recommendation for patients who progress from first-line or second-line EGFR/ALK inhibitors?

 

  Maximilian Hochmair教授:对于这些患者,活检是非常有帮助的。我认为,当患者不再有合适的靶向药物可选择时,应该根据PD-L1表达情况决定继续化疗还是免疫治疗。在中国,你们已经开始使用免疫治疗了吗?

  Prof. Maximilian Hochmair: In these patients, biopsies are very helpful. I think, in patients who have no target therapy anymore and no target anymore, you should decide from PD-L1 staining whether to go for chemotherapy or immunotherapy. In China, do you use immunotherapy already?

 

  周彩存教授:我们还没有开始,目前只有临床试验。关于免疫治疗,您强调需要检测PD-L1表达。在ASCO和ESMO年会上,我们看到了OAK试验(atezolizumab对比多西他赛),atezolizumab在不同人群(PD-L1表达阳性或阴性)均有获益。所以,如果选择atezolizumab,也许检测不是必要的。

  Prof. Caicun Zhou: No, not yet. We just have trials. You talk about the testing of PD-L1 expression for immunotherapy. At ASCO and ESMO, we saw the OAK trial with atezolizumab versus docetaxel. In that trial, we saw benefits were observed across different populations of patients with positive and negative PD-L1 expression. So if you select atezolizumab, perhaps no test is necessary.

 

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