Ruffini教授：关于降阶梯，核心仍在于以生物标志物筛选患者。若明确某种疗法对患者无效，则可考虑降阶梯治疗。但据我所知，目前这个问题尚无定论，需要通过研究数据来建立假设、形成证据。

周教授：目前我们缺少足够的研究数据来解答这一关键问题，但可以明确的是，新型化合物的开发是提高疗效的关键。中国研究者正在探索双特异性抗体联合化疗的围手术期治疗方案，研究数据显示其安全性良好，但疗效仍需进一步验证。此外，TROP2抗体偶联药物（ADC）德曲妥珠单抗联合免疫治疗的II期研究正在进行，同时，多个新型化合物也在新辅助治疗领域展开研究。双特异性抗体、双特异性ADC等新型药物层出不穷，各种联合方案正在探索中。

 

任何治疗方案都需要平衡疗效和安全性，还要考虑经济毒性，因为许多患者无法承担费用高昂的治疗方案。合理的治疗方案应权衡疗效、毒性和经济毒性。

 

Ruffini教授：不同国家的医疗政策差异也需考虑。例如在意大利，药物费用由国家卫生系统报销，患者无需为治疗药物付费，但其他很多国家并非如此。周教授提出的“经济毒性”概念很有价值——毒性意味着成本，不仅是药物本身的费用，还包括治疗并发症产生的费用，这个概念值得在全球范围深入探讨。

 

周教授：完全同意。在评估新疗法的疗效时，不应仅关注pCR率，更需要重视长期生存获益（包括中期生存和长期生存数据）。关键问题在于，有多少患者能通过该疗法实现临床治愈。目前围手术化疗联合免疫治疗的pCR率约20-25%，能否进一步提升至40-50%？疗效评估不应局限于部分缓解（PR）等短期指标，而应以治愈率为核心。

 

Ruffini教授：患者追求的是治愈和长期生存，而非单纯的病理完全缓解。当然二者可能存在关联，但这种关联尚不明确。

 

Dr.Ruffini:I can reply for the first part，and probably Professor Zhou is the expert for the second part.For the first part，again we come back to the previous discussion.Once again，the selection of these patients depends on biomarkers.If we know that this treatment is not effective then OK，we can de-escalate.But so far，to my knowledge，we do not know.So，we need studies and we need data in order to make assumptions to make evidence.If there are any ongoing trials，I think Professor Zhou can explain.

 

Dr.Zhou:That is a great question.So far，we do not have much data to answer the question，but we do know that we need novel compounds or agents to improve efficacy.In China，we have bispecifics to combine with chemo in the perioperative setting.So far，the safety is quite good，but we need better efficacy.We also have a study investigating ADC-based immunotherapy with the TROP2 datopotamab deruxtecan ADC combined with IO in a phase II study.We are waiting for the result of this study.There are several novel compounds also being studied in the neoadjuvant setting.So far，I will say that this combination of therapy is acceptable，but we need the efficacy data，especially a phase III trial to confirm the efficacy and safety profile.Anyway，there are so many novel compounds.We have bispecifics.We have bispecific ADCs.Maybe the combination of these compounds can further improve efficacy.For any therapy，we should balance efficacy and safety–the treatment should be quite effective，but not too toxic.We also need to consider the economic toxicity.That is very important.Nowadays，expensive therapies are not accessible to many patients.We need to consider the balance between the efficacy，safety profile and economic toxicity.That is my thoughts.

 

Dr.Ruffini:And probably，different countries have different policies.For example，in Italy，all of these drugs are reimbursed by the National Health System.The state，of course，has a considerable economic burden.The patients don’t pay for the drug.This is what happens in Italy of course，but every country has different healthcare policies.This is something that has to be taken into account.I really liked the concept that Professor Zhou raises–that of economic toxicity.If there is a toxicity，of course there is a cost.It is a cost for the state to take care of the complications from the toxicity，not only the cost of the compound，but also the cost of treating and curing the adverse effects.I really like this this concept.Of course，we need to have a global discussion on that.This is something that has to be taken into account.

 

Dr.Zhou:I totally agree.When we look at efficacy，we should counter the pCR rate.We also need to consider long-term survival，not only medium-term survival.We should consider how many patients can be cured with a novel therapy.Nowadays，the pCR rate with chemo-IO is about 20-25%.Can we increase the rate to 40-50%?We need to look at efficacy data for，not just partial response，nPR，etc.，but cure rates are also important.

 

Dr.Ruffini:What patients want is to be cured and to live long lives，not to have a complete pathologic response.Of course，maybe they are correlated，but we don’t know.