深刻解讀：鼻咽癌免疫治療的現在及未來展望
編譯：腫瘤資訊來源：腫瘤資訊
專家介紹：
許駿教授
國立台灣大學醫學院附屬總醫院
許駿教授對惡性腫瘤的免疫治療有很深的造詣，作為通訊作者發表了第一項鼻咽癌Pembrolizumab免疫治療的Ib期臨床試驗(Keynote-028)。本次大會許駿教授就鼻咽癌免疫治療的現在及未來展望進行了深刻的解讀。
1. 早期鼻咽癌治療效果極佳，但是晚期患者的生存仍不理想，尤其是複發轉移患者。然而這些患者經常面臨著一線化療失敗后無葯可選的局面，因此急需尋找有效的治療方式。免疫作為近年來新興的一種治療方式，在肺癌、黑色素瘤等癌種中取得了巨大的成功，而在鼻咽癌中的證據仍是空白；
2. 鼻咽癌免疫治療有著充分的理論依據：① 90%以上鼻咽癌與EB病毒感染有關，而EB病毒相關蛋白具有免疫原性；② EB病毒慢性感染與腫瘤微環境中的炎症相關；③鼻咽癌腫瘤細胞高表達PD-L1。
3. Keynote-028研究結果顯示：入組27例一線治療失敗的複發或轉移患者，客觀反應率(ORR)達到25.9%，中位PFS 6.5個月，中位OS達到16.5個月，療效令人滿意，為臨床治療帶來新的手段。
4. 免疫治療同樣面臨著許多問題：①如何鑒別高風險和最大獲益人群？②如何鑒定預測免疫治療療效的生物標誌物？依賴於腫瘤細胞PD-L1的表達還是免疫細胞的？③ 不同免疫治療藥物聯合使用的前景如何？；④免疫治療的毒副反應同樣不能忽視。
英文原文
Immune checkpoint inhibitor therapy for nasopharyngeal carcinoma: current status and future perspective
Chiun Hsu, MD, PhD
Graduate Institute of Oncology, National Taiwan University (NTU) College of Medicine
Department of Oncology, NTU Hospital
NTU Cancer Center
Professor Hsu』s research interest mainly focus on cancer immunotherapy and he has made many great achievements. He as the corresponding author pioneered the first clinical trial of immune checkpoints inhibitors which is known as the Keynote-028 study in nasopharyngeal carcinoma, and this study was published on Journal of Clinical Oncology last year. Professor Hsu will talk about the current status and prospect of immune checkpoint inhibitors in nasopharyngeal carcinoma at this conference.
1. Treatment outcomes of early-stage nasopharyngeal carcinoma are usually excellent; however, control of advanced disease, especially recurrent and metastatic disease, still remains unsatisfactory. Actually, there is no standard and effective treatment after first-line chemotherapy for recurrent and metastatic disease. Therefore, it』s urgent to identify novel and effective therapeutic strategies. In recent years, immune checkpoint inhibitors have been proven an effective, safe and promising treatment for patients failing standard chemotherapy in many malignancies, like non-small cell lung cancer and melanoma. However, clinical evidence regarding immunotherapy in nasopharyngeal carcinoma is very rare.
2. There are sufficient early rationale for applying immune checkpoint inhibitors in nasopharyngeal carcinoma such as : (i) the immunogenicity of Epstein-Barr virus (EBV) viral proteins; (ii) the inflamed tumor microenvironment is associated with chronic EBV infection; (iii) the high proportions of tumor cells with programmed death ligand 1 (PD-L1).
3. In total, 27 patients with recurrent or metastatic nasopharyngeal carcinoma who failed first-line treatment were included in the Keynote-028 study, and the results revealed the ORR is 25.9%, median progressive-failure survival (PFS) is 6.5 months and the median overall survival (OS) is 16.5 months. There promising outcomes indicate that immune checkpoint inhibitor may serve as a new treatment strategy for recurrent/metastatic nasopharyngeal carcinoma.
4. However, there are also many concerns about immune checkpoint inhibitors. First, how to identify the high-risk and most beneficial population? Second, how to identify the predictive biomarkers for immune checkpoint inhibitors? Should we depend on the PD-L1 expression on tumor cells or immune cells? Third, how about the prospect of combination of immune checkpoint inhibitors? Moreover, immune checkpoint inhibitors-related toxicities are also great challenges and should not be ignored.
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