编者按:本次CSCO-JSMO/KSMO 联合专场聚焦“亚洲高发肿瘤临床研究”这一热点话题,邀请中日韩三国顶级专家,探讨胃肠道肿瘤临床研究领域的最新进展。韩国首尔国立大学医学院的Yung-Jue Bang教授介绍了胃癌的免疫治疗进展,日本东部国家癌症中心医院的Atsushi Ohtsu教授针对上消化道癌的新药物/转化研究做了精彩的报告。《肿瘤瞭望》特邀两位主席展开深入对话,探讨如何提高胃癌的临床诊疗和研究水平。
(左:Atsushi Ohtsu教授 右:Yung-Jue Bang教授)
Oncology Frontier: As the chairman of this CSCO-JSMO/KSMO joint special session focusing on the "Clinical study of High incidence tumors in Asia", can you talk about some main clinical research developments of your own concern?
Dr. Bang: For gastric cancer, in the past we have used cytotoxic chemotherapy and targeted agents. Now we have immunotherapy. It has been shown that anti-PD-1 antibodies are effective as third-line treatment for patients with advanced gastric cancer.
Dr Ohtsu: The progress of immunotherapy is now very rapid. It is a great area for clinical study. In biomarker research for immunotherapy, the anti-PD-1 antibodies achieve a very good response of long duration, but the percentage of responsive cases is still <20%, so this is an area of research that needs to expand.
Oncology Frontier: In terms of the current status and prospects of immunotherapy in the field of gastric cancer, what are your main views respectively?
Dr Ohtsu: As I suggested, biomarker research is the most important point for the selection of patients for immunotherapy. Additionally, combination therapy with the anti-PD-1 antibodies will increase the efficacy of therapy for gastric cancer patients.
Dr Bang: Combinations of anti-PD-1 antibodies and other agents are actively being explored at this time, including with other immune checkpoint inhibitors, targeted agents, or chemotherapy. There are at least three ongoing Phase III trials at the moment to test the effectiveness of the combination of anti-PD-1 antibody and chemotherapy. The results will be available very soon, and we expect those trial will be positive - resulting in helping more patients with advanced gastric cancer. Also, anti-PD-1 antibodies are being tested in the adjuvant setting and the neoadjuvant setting, so the scope of immunotherapy in gastric cancer will expand in the future.
Oncology Frontier: At present, there is still a lot of controversy about perioperative treatment of gastric cancer. Could you give us a brief account of main progress in this area?
Dr Bang: I should mention the differences in surgical techniques between Asian countries and Western countries. In Asia, we believe our surgical techniques are very good, and we use post-operative chemotherapy to improve the cure rate. However, in the West, surgical techniques are less good and a perioperative approach is effective, so this approach is preferred in the Western countries. As I have mentioned, immunotherapy is also being tested in these settings.
Dr Ohtsu: In Japan, a recent topic of interest is the combination of S-1 (tegafur, gimeracil, and oteracil) with docetaxel, which achieves a significant improvement in post-operative adjuvant settings. That will be standard treatment for stage 2/3 gastric cancer in Japan, and a great advance. Of course, we are also participating in the adjuvant trials with anti-PD-1 antibodies, as Professor Bang mentioned. We hope this leads to an improvement in the cure rate for gastric cancer patients.
Oncology Frontier: We know that the cancer gene screening project for digestive tract tumors has been launched in Japan. What do you think is the significance to the clinical diagnosis and treatment of gastrointestinal tumors?
Dr Ohtsu: We launched the nationwide gene screening project, SCRUM-Japan, three years ago. We have enrolled approximately 10000 patients for lung and GI cancers. Genetic profiling is well underway for the GI cancers, including gastroesophageal cancers. There are driver genes, particularly in gastric cancer, that are being focused on in studies such as EGFR and c-MET, and there are some very rare cases with ROS1 and ALK, as have been seen with lung cancer. So we have data for only a tiny fraction of all the driver genes, but these patients achieve good responses to the relevant targeted agents, but these populations are very small and we need to have more efficacious agents for gastric cancer. There are many driver genes in colorectal cancer and in the joint session here at CSCO, there will be discussions about several clinical trials underway looking at targeted agents for colorectal cancer.
Dr Bang: We started a similar nationwide program in Korea last year.We need more time to accumulate more data.
《肿瘤瞭望》:您二位作为这次CSCO-JSMO/KSMO 联合专场的主席,聚焦“亚洲高发肿瘤临床研究”这一热点话题,您能否分别谈谈各自关注的主要临床研究进展呢?
Yung-Jue Bang教授:对于胃癌的全身治疗,过去我们可以选择细胞毒性化疗和靶向药物,现在又有了免疫治疗。已经有研究表明,抗PD-1抗体作为晚期胃癌患者的三线治疗有效。
Atsushi Ohtsu教授:免疫治疗的进展非常迅速,是一个很好的临床研究领域。在免疫治疗相关的生物标志物研究中,PD-1抗体能够取得持续缓解,然而能够获得肿瘤应答的患者不到20%,因此还需进一步开展研究。
《肿瘤瞭望》:就免疫治疗在胃癌领域的现状和前景而言,您的主要看法是?
Atsushi Ohtsu教授:生物标志物研究是筛选适合免疫治疗患者最重要的一环。另外,与抗PD-1抗体的联合治疗将增加胃癌患者的疗效。
Yung-Jue Bang教授:目前正在积极探索抗PD-1抗体和其他药物的组合,包括其他免疫检查点抑制剂,靶向药物或化疗药物等。目前至少有三项正在进行的III期临床试验正在评估抗PD-1抗体和化疗联合治疗的有效性。结果很快就会公布,我们期待这些试验取得阳性结果,从而使更多晚期胃癌患者获益。此外,抗PD-1抗体正在胃癌的辅助治疗和新辅助治疗领域中进行评估应用,因此胃癌的免疫治疗范围未来还将进一步扩大。
《肿瘤瞭望》:目前关于胃癌的围手术期治疗尚存在很多争议,您能否给我们介绍一下这方面的主要进展?
Yung-Jue Bang教授:亚洲国家和西方国家在手术技术方面存在差异。亚洲的外科医生对自己的手术技术非常自信,主要通过术后化疗来提高治愈率。然而,西方的手术技术要略逊一筹,因此围手术期治疗在西方国家是首选。正如我所提到的,免疫疗法也正在胃癌的围手术期治疗中进行评估。
Atsushi Ohtsu教授:在日本,目前最热门的话题是S-1与多西紫杉醇的组合用于胃癌的术后辅助治疗使患者生存明显改善,将成为日本II/III期胃癌的标准治疗,取得了很大的进展。当然,我们也开展了抗PD-1抗体的辅助治疗试验,希望可以改善胃癌患者的治愈率。
《肿瘤瞭望》:目前日本已经启动了消化道肿瘤的癌症基因筛查项目,您认为这对于消化道肿瘤临床诊疗实践有何重要的意义?
Atsushi Ohtsu教授:三年前,我们启动了全国基因筛查项目SCRUM-Japan,已招募了约10000例肺癌和胃肠癌患者。正在进行胃肠道肿瘤基因谱分析,包括胃癌和食管癌等。有一些驱动基因,尤其是在胃癌中,正在研究EGFR和c-MET等突变,肺癌中也有一些非常罕见的ROS1和ALK突变病例。虽然我们只有所有驱动基因的一小部分数据,这些患者对相关靶向药物的反应良好,然而这些人群非常少,我们需要寻找到更有效的胃癌药物。在结直肠癌中也存在许多驱动基因,在本次CSCO联合会议中,我们也重点讨论了正在进行的几种针对结直肠癌靶向治疗药物的临床试验。
Yung-Jue Bang教授:去年在韩国开展了类似的全国性项目,需要更长的时间来积累更多的数据。