周彩存教授：这是一个非常好的问题。目前，埃万妥单抗（amivantamab）联合化疗是全球标准。我们必须使用埃万妥单抗联合化疗治疗晚期EGFR ex20ins突变患者。未来，我们可能会有像WU-KONG研究这样的靶向药物。我们正在等待该研究的数据。但从目前这些TKI在后线治疗中的数据来看，PFS并不长。所以可能需要联合治疗。埃万妥单抗联合化疗已被PAPILLON研究验证可行。那么TKI联合化疗呢？TKI联合埃万妥单抗呢？您怎么看？

 

Prof.Caicun Zhou：That’s a very good question.So far，amivantamab plus chemotherapy is the standard of care worldwide.We have to use amivantamab plus chemotherapy to treat advanced patients with EGFR exon 20 insertion.In the future，maybe we will have targeted agents like the WU-KONG studies.We are just waiting for the data of that study.But when we look at the duration of these TKIs so far in the second-line setting，the PFS is not so long.So maybe we need combination.The combination of amivantamab plus chemotherapy is already feasible，approved by the PAPILLON study.How about TKI plus chemotherapy?TKI plus amivantamab?What’s your idea?

 

Sanjay Popat教授：我认为这完全正确。目前，埃万妥单抗联合化疗是获批方案，有III期数据支持，但TKI也显示出非常好的活性。所以毫无疑问，未来我们将有舒沃替尼、zipalertinib等选择，还有许多其他药物正在开发。一个非常有趣的领域是，我们是否需要根据exon 20的基因型进行个体化治疗？因为其中一些药物可能对某些loop区或C-螺旋区突变类型显示出更好的疗效。我认为这是一个不断发展的领域。我们目前还没有足够大的样本量来对基因型-疗效关系做出有信心的预测。但在未来几年，随着这些数据集的积累，我们将不得不开始考虑个体突变状态。这又回到了我们之前讨论的一点：在exon 20领域，我们必须使用NGS，因为如果只做PCR，我们无法捕获这些个体基因型。展望未来，我们将面临埃万妥单抗、TKI单药或化疗联合TKI等多种选择。我们如何序贯？如何考虑联合？我们甚至可能看到ADC在这一领域的数据。TKI联合ADC无疑是合理的组合。我们需要思考如何设计这些试验。周教授，我相信这方面有很多正在进行的探索。

 

Prof.Sanjay Popat：I think this is completely a correct statement.At the moment，amivantamab plus chemo is the approved regimen.We have phase III data supporting its usage，but the TKIs are showing very good activity.So undoubtedly，I think in the future，we will have options like sunvozertinib，zipalertinib，and there are many others that are being developed as well.One of the really interesting areas is，do we need to individualize based on the genotype for exon 20?This is a very interesting topic，because some of these drugs are perhaps showing greater efficacy for certain loop or C-helix types of mutations than others.I think this is an evolving area.We don’t have such large numbers to be able to confidently make predictions about genotype-efficacy relationships at this point.But over the next few years，as these data sets evolve，we’re going to have to start thinking about individual mutation status.And this goes back to one of the points we were saying beforehand:in the exon 20 space，we have to use NGS，because we won’t pick up these individual genotypes if we’re doing PCR.Now，if we think about the future，we are going to have a future where the options will be amivantamab，TKI monotherapy，or chemo plus TKI.How do we then sequence?How do we then think about combinations?We may even have some data coming through on ADCs in this space as well.A combination of TKI plus ADC would make absolute sense.We need to think about how we generate these trials.Doctor Zhou，I’m sure there’s a lot of activity ongoing.

 

周彩存教授：我们对埃万妥单抗联合TKI的探索非常感兴趣。有一个小样本量的I期试验正在进行中，目前尚无数据。TROP2 ADC在EGFR突变肺癌中非常敏感。那么TROP2 ADC联合埃万妥单抗，或TROP2 ADC联合TKI呢？我们正在等待这些研究的数据。

 

Prof.Caicun Zhou：We are quite interested in the combination of amivantamab plus TKI.There is a small sample size phase I trial ongoing.So far，we don’t have the data.TROP2 ADC is very sensitive in EGFR-mutant lung cancer.How about TROP2 ADC plus amivantamab，or TROP2 ADC plus TKI?We just wait for the data of the studies.