摘要：由徐瑞华教授作为全球Leading PI开展的一项全球多中心、随机双盲、Ⅲ期临床研究（RATIONALE-305研究）证实，替雷利珠单抗联合化疗相较安慰剂联合化疗可以显著延长晚期胃癌患者的总生存期，为晚期胃癌患者一线治疗提供了新的治疗选择。在2024年欧洲肿瘤
由徐瑞华教授作为全球Leading PI开展的一项全球多中心、随机双盲、Ⅲ期临床研究（RATIONALE-305研究）证实，替雷利珠单抗联合化疗相较安慰剂联合化疗可以显著延长晚期胃癌患者的总生存期，为晚期胃癌患者一线治疗提供了新的治疗选择。在2024年欧洲肿瘤内科学会亚洲年会（ESMO ASIA 2024）上公布了亚洲患者的对患者报告的结局（PRO）的分析结果。《肿瘤瞭望消化时讯》在大会现场邀请日本国立癌症研究中心医院的Ken Kato教授进行了解读。
肿瘤瞭望消化时讯：在本次会议上，您介绍了RATIONALE-305研究的一些结果。能否介绍一下这项研究的概况和主要结果？
Kato 教授：RATIONALE-305研究表明，与化疗加安慰剂组相比，化疗加抗PD-1抗体替雷利珠单抗一线治疗可显著晚期胃癌或胃食管结合部腺癌患者的OS和PFS，其疗效与其他抗PD-1抗体（如纳武利尤单抗和帕博利珠单抗）类似。目前，该研究结果已经发表在相关文献中。在本次EMSO ASIA会议上，我介绍了对亚洲亚组的患者报告结局（PRO）的分析。PRO数据显示，替雷利珠单抗组的疼痛和/或不适有所改善，这些结果进一步支持了化疗加替雷利珠单抗一线治疗可使胃癌患者的临床改善。
Dr Kato: The RATIONALE-305 study shows an improvement in OS and PFS for patients in first-line with advanced gastric or gastro-esophageal junction adenocarcinoma. The improvement was seen in the chemotherapy plus tislelizumab arm compared to the chemotherapy plus placebo arm. This is a significant improvement with tislelizumab as the PD-1 antibody, similar to other anti-PD-1 antibodies, like nivolumab and pembrolizumab. The results have already been published in the literature. Now, at this EMSO Asia Conference, I presented the results of the patient-reported outcomes (PROs) in the Asian subgroup patients. The PRO results showed an improvement in pain and/or discomfort in the tislelizumab arm, and these results support the results of the clinical improvements seen with chemotherapy plus tislelizumab for first-line in gastric cancer patients.
肿瘤瞭望消化时讯：免疫疗法联合化疗与临床实践中单独化疗的毒性特征相比如何？临床我们应该如何管理？
Kato 教授：我们已经熟悉化疗加PD-1疗法对胃癌以及胃食管癌患者的影响。免疫检查点抑制剂的毒性特征与单独化疗完全不同，例如，患者会出现皮肤毒性和内分泌功能障碍，有时甚至会表现为药物性肺炎。但在大多数情况下，这些都可以通过使用类固醇或其他免疫抑制剂来控制。目前我们能够在日常实践中管理免疫检查点抑制剂的毒性。
Dr Kato: We were already familiar with chemotherapy plus PD-1 therapy for gastric cancer patients, as well as gastro-esophageal cancer patients. The toxicity profile for the immune checkpoint inhibitors is quite different from that of chemotherapy alone, for example, the skin toxicity and endocrine dysfunction, and sometimes patients suffer from drug-induced pneumonia. But in most cases, this can be managed with administration of steroids or other immunosuppressive agents. So now, we are able to manage toxicity from the immune checkpoint inhibitors in daily practice.
肿瘤瞭望消化时讯：免疫检查点抑制剂生物标志物的研究现状如何？如何选择将从免疫疗法中受益的患者？
Kato 教授：目前正在进行的大多数临床试验显示，无论PD-L1状态如何，抗PD-1抗体都有临床获益，但在PD-L1阳性患者中的疗效更佳。PD-L1表达低的患者对抗PD-1抗体的获益较小。无论PD-L1低表达人群的证据如何，我们都可以通过CPS（联合阳性评分） 免疫组化分析确定那些适用PD-L1免疫检查点抑制剂的患者。未来，免疫治疗与新药和其他联合疗法相结合将有助于提高疗效，即使对于PD-L1低人群也是如此。这也是我们未来的期望。
Dr Kato: There are trials ongoing. Most of the clinical trials show clinical benefit regardless of PD-L1 status, but the magnitude of anti-PD-1 antibody efficacy is better in the PD-L1-positive patients. The patients with low PD-L1 expression show less benefit with anti-PD-1 antibodies. Regardless of the obvious evidence for the PD-L1-low population, we can identify those patients who would benefit more with PD-L1 immune checkpoint inhibitors with CPS (combined positive score) immunohistochemistry analysis. In the future, immunotherapy combined with newer drugs and in other combination therapies will be helpful for efficacy, even for the PD-L1-low population. We hope so.
来源：肿瘤瞭望消化时讯