在肺癌治療、特別是EGFR突變的晚期非小細(xì)胞肺癌(NSCLC)治療領(lǐng)域,ASCO 2015展示了哪些重要的研究進展?
Lynch教授:本次ASCO會議展示了肺癌領(lǐng)域的諸多研究進展,比如在5月31日上午口頭報告專場,AZD9291一線治療EGFR突變晚期NSCLC顯示出非常好的抗腫瘤活性;Rociletinib治療T790M突變陽性NSCLC患者也顯示出較好效果。這兩種新藥給EGFR突變患者更多治療選擇。相比美國,中國NSCLC患者中EGFR突變更加常見,針對這類患者的治療更重要。
石遠(yuǎn)凱教授:根據(jù)中國的多中心研究結(jié)果,中國晚期肺腺癌患者中EGFR突變陽性者超過50%,而西方國家的比例大約是17%。因此,EGFR-TKI在中國有更多的應(yīng)用空間。
Lynch教授:本屆ASCO會議有一點讓我感到失望,本次會議展示了PD-1/PD-L1抑制劑免疫治療的成果,卻沒有展示EGFR突變患者PD-1/PD-L1抑制劑治療有多少獲益,這方面還需要更多的臨床試驗,特別是在亞洲。
石遠(yuǎn)凱教授:我同意您的觀點,目前證明有效的PD-1/PD-L1抑制劑是由西方國家藥企研發(fā),中國的研究剛剛起步。目前我們正在開展轉(zhuǎn)化研究以確認(rèn)EGFR突變陽性同時PD-1/PD-L1陽性表達患者的比例,目前還沒有確切數(shù)據(jù),但不久的將來我們會宣布試驗結(jié)果。
NSCLC免疫治療是2015 ASCO 會議熱點之一,您如何評價PD-1/PD-L1抑制劑的療效?
Lynch教授:免疫療法治療癌癥的效果令人振奮,其治療EGFR突變患者的療效還不清楚。本次ASCO會議展示了PD-1/PD-L1抑制劑治療黑色素瘤的良好療效。這一類藥物都比較有前景。
石遠(yuǎn)凱教授:請問Lynch教授,您如何看待EGFR-TKI聯(lián)合PD-1/PD-L1抑制劑治療NSCLC患者?
Lynch教授:目前還沒有確切答案,許多EGFR-TKI聯(lián)合PD-1/PD-L1抑制劑治療的試驗正在進行中,我們需要等待研究數(shù)據(jù)。
在EGFR突變陽性肺癌一線治療方面有哪些新的選擇?您如何評價中國自主創(chuàng)新藥物埃克替尼?
Lynch教授:我多年前就對??颂婺嵊兴私?,是因為貝達藥業(yè)在康涅狄格州紐黑文設(shè)有公司,就在耶魯。我曾與許多??颂婺岬难邪l(fā)者和企業(yè)領(lǐng)導(dǎo)接觸過。??颂婺岬难芯繑?shù)據(jù)令我印象深刻,不僅僅是療效,其毒性數(shù)據(jù)也比較好,腹瀉、皮疹等副作用的發(fā)生率較低。我認(rèn)為??颂婺嵋彩荅GFR突變陽性NSCLC患者一線治療的良好選擇。
石遠(yuǎn)凱教授:埃克替尼為中國自主研發(fā)、亞洲首個EGFR-TKI原創(chuàng)新藥。埃克替尼III期ICOGEN研究[隨機、雙盲雙模擬、平行對照、多中心評價??颂婺岷图翘婺嶂委熂韧邮苓^一個或兩個化療的局部晚期或轉(zhuǎn)移的非小細(xì)胞肺癌患者的療效和安全性III期臨床試驗]被接受為2011年世界肺癌大會(WCLC)的口頭報告,在2013年腫瘤領(lǐng)域影響因子最高的《柳葉刀.腫瘤》分冊上發(fā)表。ICOGEN III期研究顯示??颂婺崤c吉非替尼二、三線治療晚期NSCLC患者的療效相當(dāng),但??颂婺犸@示出更好的安全性,總體不良事件發(fā)生率減少,患者耐受性更佳。上市后IV研究(ISAFE研究)與ICOGEN 研究的結(jié)果一致,顯示出良好的療效。
目前正在開展??颂婺嵋痪€治療與化療對比的CONVINCE研究,研究進展順利,不久之后會發(fā)布研究結(jié)果。2014年,??颂婺岖@得了中國的國家食品藥品監(jiān)督管理局(SFDA)批準(zhǔn)的一線治療EGFR突變晚期NSCLC患者的適應(yīng)證。CONVINCE研究試驗設(shè)計具有獨特性,在化療對照組(培美曲塞+順鉑)又加上了維持治療,所以結(jié)果更值得期待。
未來應(yīng)如何改進肺癌治療策略?
Lynch教授:在過去10年中,肺癌領(lǐng)域取得諸多研究成果。目前已有 5 種治療EGFR突變肺癌患者的藥物,正在對免疫治療EGFR突變肺癌的潛力進行研究。問題是,對患者進行分子檢測后,我們是否有可用的藥物針對分子機制進行治療?目前需要更多臨床研究的是RAS突變肺癌患者的治療。美國有30%腺癌患者有RAS突變,但是我們治療RAS突變肺癌的藥物極其有限。
石遠(yuǎn)凱教授:在中國的RAS突變肺癌患者比西方國家少。但是下一步的確需要針對這類患者開展更多研究工作。
近年來,中國原創(chuàng)性藥物的發(fā)展突飛猛進,您如何看待中國研發(fā)創(chuàng)新藥物的能力?
Lynch教授:我強烈認(rèn)為,中國在藥物研發(fā)方面做了許多工作,并投入大量資金。中國在基因組研究和理解癌癥基因機制方面做了很多工作,使中國患者獲益,并有利于新藥研發(fā)。
石遠(yuǎn)凱教授:中國本土藥企不僅致力于仿制藥研發(fā),也致力于創(chuàng)新藥物研發(fā)。目前越來越多的中國醫(yī)生參與腫瘤藥物的創(chuàng)新研發(fā)和轉(zhuǎn)化研究的工作。
Lynch教授:中國在白血病藥物創(chuàng)新研發(fā)方面成果顯著,也有其他領(lǐng)域的重要創(chuàng)新藥物成果。在這方面我們應(yīng)開展合作。最近有何創(chuàng)新藥物研發(fā)進展?
石遠(yuǎn)凱教授:在中國,一些創(chuàng)新藥物由本土企業(yè)獨立研發(fā),一些創(chuàng)新藥物為中外制藥企業(yè)合作研發(fā)。有些癌癥在國外較少見,而中國有龐大的患者群體。例如中國有非常多的肝細(xì)胞瘤、鼻咽癌和食管癌患者,一半以上的食管癌發(fā)生在中國。針對這類腫瘤的藥物研發(fā)中國醫(yī)生做了大量工作。
比如,在2015年ASCO會議上,來自中國的臨床研究“埃克替尼二線治療EGFR過表達或擴增的晚期食管癌的II期單臂試點試驗”在壁報專場展示。試驗入組患者為活檢確診有 EGFR 過表達[免疫組織化學(xué)(IHC)3 +]或擴增[熒光原位雜交(FISH)陽性]晚期食管癌鱗癌患者,患者已經(jīng)接受鉑類為基礎(chǔ)的一線化療。試驗結(jié)果良好,初步研究結(jié)果提示,??颂婺岫€治療 EGFR過表達或擴增的晚期食管癌展現(xiàn)出良好的抗腫瘤活性和安全性。
Lynch教授:試驗結(jié)果良好,真是太好了!
專家介紹
Thomas James Lynch, MD,國際著名肺癌專家,靶向抗癌藥的國際權(quán)威,肺癌領(lǐng)域新的治療方法研究的佼佼者,康涅狄格洲紐黑文耶魯腫瘤中心的主任、康涅狄格洲紐黑文Smilow腫瘤醫(yī)院的主任。他對肺癌治療的貢獻已獲得世界認(rèn)可,作為EGFR突變的首位發(fā)現(xiàn)者之一,2013年被授予癌癥護理巨人獎(Giants of Cancer CareTM award)。Thomas lynch教授在2004年報告了EGFR基因突變可預(yù)示EGFR酪氨酸激酶抑制劑治療,掲開了肺癌個體化治療的序幕。
石遠(yuǎn)凱教授,腫瘤學(xué)博士、腫瘤內(nèi)科主任醫(yī)師、博士研究生導(dǎo)師,中國醫(yī)學(xué)科學(xué)院腫瘤醫(yī)院副院長,國家抗腫瘤藥物臨床研究機構(gòu)副主任,抗腫瘤分子靶向藥物臨床研究北京市重點實驗室主任,中國醫(yī)師協(xié)會腫瘤醫(yī)師分會會長,中國藥學(xué)會抗腫瘤藥物專業(yè)委員會主任委員,中國抗癌協(xié)會常務(wù)理事、學(xué)術(shù)部部長,中國抗癌協(xié)會腫瘤臨床化療專業(yè)委員會主任委員,中國抗癌協(xié)會淋巴瘤專業(yè)委員會副主任委員,中國抗癌協(xié)會癌癥康復(fù)會副主任委員,中國老年學(xué)學(xué)會老年腫瘤學(xué)專業(yè)委員會副主任委員,中國藥學(xué)會藥物臨床評價研究專業(yè)委員會副主任委員,中國抗癌協(xié)會臨床腫瘤學(xué)協(xié)作專業(yè)委員會(CSCO)執(zhí)行委員,亞洲臨床腫瘤學(xué)會副主席,國家食品藥品監(jiān)督管理局藥品審評專家,“重大新藥創(chuàng)制”科技重大專項GCP組和化藥組責(zé)任專家。
中英對照原文
Oncology Frontier: Dr Lynch, as a pioneer in the EGFR-mutated cancer field, what progress have we have seen at this 2015 ASCO Annual Meeting?
《腫瘤瞭望》:在肺癌治療、特別是EGFR突變的晚期非小細(xì)胞肺癌(NSCLC)治療領(lǐng)域,ASCO 2015展示了哪些重要的研究進展?
Dr Lynch: We have had a lot of good examples of progress at this year’s ASCO meeting. We have learned that AZD9291 looks like having excellent activity as first-line treatment in patients with EGFR-mutated lung cancer. We have learned that the Clovis compounds also have activity in T790M-mediated resistant tumors and maybe some patients without resistance. These two new drugs, in addition to afatinib, icotinib, erlotinib and gefitinib will give doctors more choice. In China, I would imagine the disease is a bigger issue for you than in the United States given how much more common EGFR-related mutations are in China.
Lynch教授:本次ASCO會議展示了肺癌領(lǐng)域的諸多研究進展,比如在5月31日上午口頭報告專場,AZD9291一線治療EGFR突變晚期NSCLC顯示出非常好的抗腫瘤活性;Rociletinib治療T790M突變陽性NSCLC患者也顯示出較好效果。除了阿法替尼、埃克替尼、厄洛替尼和吉非替尼,這兩種新藥給EGFR突變患者更多治療選擇。相比美國,中國NSCLC患者中EGFR突變更加常見,針對這類患者的治療更重要。
Dr Shi: Because of the genetic background, the disease differs between the Caucasian and Oriental populations. For EGFR mutations, patients in the Caucasian population make up about 17%, but from our Chinese multi-center study, we found 50% of our adenocarcinoma patients had the EGFR-active mutation. So I believe the EGFR TKIs will be used more frequently in Chinese adenocarcinoma patients because of the higher incidence of the EGFR-active mutation.
石遠(yuǎn)凱教授:這與不同人種的基因背景差異有關(guān)。根據(jù)中國的多中心研究結(jié)果,中國晚期肺腺癌患者中EGFR突變陽性者超過50%,而西方國家的比例大約是17%。因此,EGFR-TKI在中國有更多的應(yīng)用空間。
Dr Lynch: I agree. One thing I was disappointed about here at ASCO was that we had the presentation on the PD-1/PD-L1 study and it didn’t look like the EGFR mutation group seemed to benefit as much. We aren’t completely certain of that yet as the numbers are small and more study is needed particularly in Asia.
Lynch教授:我同意您的觀點,本屆ASCO會議有一點讓我感到失望,本次會議展示了PD-1/PD-L1抑制劑免疫治療的成果,卻沒有展示EGFR突變患者PD-1/PD-L1抑制劑治療有多少獲益,這方面還需要更多的臨床試驗,特別是在亞洲。需要確認(rèn)EGFR突變陽性同時PD-1/PD-L1表達的患者占多大比例,及其采用PD-1/PD-L1抑制劑治療的獲益。
Dr Shi: The PD-1/PD-L1 therapies are developed by Western pharmaceutical companies and we are only beginning clinical study and development in China. In the future, we will have more experience and data.We are currently doing translational research to determine what percentage of EGFR-mutated patients has PD-1 expression. I don’t have precise data so far but you can expect us to announce our findings later.
石遠(yuǎn)凱教授:目前證明有效的PD-1/PD-L1抑制劑是由西方國家藥企研發(fā),中國的研究剛剛起步。目前我們正在開展轉(zhuǎn)化研究以確認(rèn)EGFR突變陽性同時PD-1/PD-L1陽性表達患者的比例,目前還沒有確切數(shù)據(jù),但不久的將來我們會宣布研究結(jié)果。
Oncology Frontier: What has been your experience with the clinical use of the PD-1 and PD-L1 therapies?
《腫瘤瞭望》:NSCLC免疫治療是2015 ASCO 會議熱點之一,您如何評價目前的PD-1/PD-L1抑制劑研究進展?
Dr Lynch: I think the PD-1 and PD-L1 drugs are very exciting in cancer. In the EGFR setting, I don’t think we know enough yet. Data presented today showed good results with melanoma, but the whole class of drugs is very promising.
Lynch教授:免疫療法治療癌癥的效果令人振奮,其治療EGFR突變患者的療效還不清楚。本次ASCO會議展示了PD-1/PD-L1抑制劑治療黑色素瘤的良好療效。這一類藥物都比較有前景。
Dr Shi: I would like to ask Dr Lynch what is your opinion on combining EGFR TKIs and PD-1/PD-L1s?
石遠(yuǎn)凱教授:請問Lynch教授,您如何看待EGFR-TKI聯(lián)合PD-1/PD-L1抑制劑治療NSCLC患者?
Dr Lynch: It’s a great question but we just don’t know yet. There are many ongoing trials now looking at combinations so we will have to wait for that data.
Lynch教授:目前還沒有確切答案,許多EGFR-TKI聯(lián)合PD-1/PD-L1抑制劑治療的試驗正在進行中,我們需要等待研究數(shù)據(jù)。
Oncology Frontier: Icotinib is China’s innovative drug for advanced EGFR mutation-positive NSCLC. The ICOGEN study, What is your comment on the efficacy of icotinib and its significance in treating EGFR mutation-positive advanced NSCLC?
《腫瘤瞭望》:您如何評價中國自主創(chuàng)新藥物??颂婺??
Dr Lynch: I have known about icotinib for many years. Because Beta Pharmaceuticals has US office in New Haven, Yale, I have chance to meet the investigators and leaders in New Haven, Connecticut. I was always impressed by the toxicity profile of icotinib. The data I have seen has always looked very encouraging. The only downside was it has to be taken three times a day but that may be more tolerable with a reduced side effect profile.
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Lynch教授:我多年前就對??颂婺嵊兴私?,是因為貝達藥業(yè)在康涅狄格州紐黑文設(shè)有公司,就在耶魯。我曾與許多??颂婺岬难邪l(fā)者和企業(yè)領(lǐng)導(dǎo)接觸過。??颂婺岬难芯繑?shù)據(jù)令我印象深刻,不僅僅是療效,其毒性數(shù)據(jù)也比較好,腹瀉、皮疹等副作用的發(fā)生率較低。唯一的不足是需要1日用藥三次,但是既然副作用降低,這點可以忍受。
Dr Shi: From the ICOGEN trial here in China, my experience is also is that icotinib has low toxicity compared to other EGFR TKIs. Even though the dosing is three times daily, it is easily tolerated by patients. We also designed the clinical trial as a first-line treatment compared to pemetrexed and cisplatin.After four cycles of induction chemotherapy, we use pemetrexed as maintenance therapy and the results will be announced soon. I am really looking forward to the results for icotinib in the first-line setting. Last year, we received Chinese FDA approval for the use of icotinib as a first-line therapy in EGFR-mutated tumors.
石遠(yuǎn)凱教授:根據(jù)ICOGEN III期研究,??颂婺岬目傮w不良事件發(fā)生率減少,即使1日用藥3次,患者也容易耐受。目前正在開展??颂婺嵋痪€治療與化療(培美曲塞+順鉑)對比的CONVINCE研究,化療對照組后續(xù)培美曲塞維持治療,該研究進展順利,不久之后會發(fā)布研究結(jié)果。我們在上市后IV研究(ISAFE研究)中獲得了一線治療的經(jīng)驗。2014年,??颂婺岖@得了中國的國家食品藥品監(jiān)督管理局批準(zhǔn)的一線治療EGFR突變晚期NSCLC患者的適應(yīng)證。
Oncology Frontier: As we have discussed, there have been several novel therapies coming available for use. What has to be done, particularly in terms of clinical trials, to further improve our treatment strategies?
《腫瘤瞭望》:未來應(yīng)如何改進肺癌治療策略?
Dr Lynch: We are very lucky in the field of lung cancer as there has been so much development over the last ten years. We now have five drugs that are effective in EGFR-mutated lung cancer. We also look at the potential of incorporating immunotherapy. The challenge for us as doctors is that when doing molecular profiling, do we have enough options to meet a patient’s molecular profile? One place I think we need more help with better clinical trials is with RAS -mutated lung cancer. In the United States, RAS makes up about 30% of our adenocarcinomas and we have very few options for treating RAS-mutated adenocarcinomas.
Lynch教授:在過去10年中,肺癌領(lǐng)域取得諸多研究成果。目前已有5種有效治療EGFR突變肺癌患者的藥物,我們也對免疫治療的潛力進行研究。問題是,對患者進行分子檢測后,我們是否有可用的藥物針對分子機制進行治療?目前需要更多臨床研究的是RAS突變肺癌患者的治療。美國有30%腺癌患者有RAS突變,但是我們治療RAS突變肺癌的藥物極其有限。
Dr Shi: In China, the incidence is less than in your population, but it is certainly the next problem to be solved for that percentage of patients.
石遠(yuǎn)凱教授:中國的RAS突變肺癌患者比西方國家少。但是下一步的確需要針對這類患者開展更多研究工作。
Oncology Frontier: In the recent times, China’s pharmaceutical industry has undergone an historic transformation from imitation to innovation. If you look forward, will China evolve into a major force in drug innovation?
《腫瘤瞭望》:近年來,中國原創(chuàng)性藥物的發(fā)展突飛猛進,原來的仿制藥大國開始了原創(chuàng)藥物研發(fā)歷程,您如何看待中國研發(fā)創(chuàng)新藥物的能力?
Dr Lynch: My opinion is very strong. We have seen tremendous commitment to science and investment in science from China. The commitment I see to genomics and understanding the genetics of cancer, for example, will be of huge benefit to China and the whole of Asia by allowing us to do profiling and bring new drugs to market.
Lynch教授:我強烈認(rèn)為,中國在藥物研發(fā)方面做了許多工作,并投入大量資金。中國在基因組研究和理解癌癥基因機制方面做了很多工作,使中國患者獲益,并有利于新藥研發(fā)。
Dr Shi: I agree. In recent years, Chinese domestic pharmaceutical companies have made huge efforts to develop drugs; not just generic drugs but also innovative agents. There are more and more drugs going to clinical trials and consequently more Chinese doctors contributing to clinical research for anti-cancer therapies and also translational medicine.
石遠(yuǎn)凱教授:中國本土藥企不僅致力于仿制藥研發(fā),也致力于創(chuàng)新藥物研發(fā)。目前越來越多的中國醫(yī)生參與腫瘤藥物的創(chuàng)新研發(fā)和轉(zhuǎn)化研究的工作。
Dr Lynch: The Chinese have lead the way in retinoic acid and arsenic in leukemia, for instance, and there are other examples of great innovation from China and that is something we should eagerly embrace and collaborate with.
Lynch教授:中國在白血病藥物創(chuàng)新研發(fā)方面成果顯著,也有其他領(lǐng)域的重要創(chuàng)新藥物研發(fā),我們應(yīng)積極開展合作。最近有何創(chuàng)新藥物研發(fā)進展?
Dr Shi: Some drugs are developed by Chinese companies; some ones by cooperating with international companies. Some cancer types are quite specific to the Chinese population such as esophageal cancer, hepatoma and nasopharyngeal carcinoma. The incidence of these cancers is quite different in Western populations. Furthermore, the incidence of cancers like nasopharyngeal cancer has spread to northern China as well as southern China over twenty years or so. So Chinese doctors need to make great efforts to do research on these cancers. For example, we have a poster at this conference describing the use of icotinib as second-line treatment for squamous cell esophageal carcinoma with good results.
石遠(yuǎn)凱教授:在中國,一些創(chuàng)新藥物由本土企業(yè)獨立研發(fā),一些創(chuàng)新藥物為中外制藥企業(yè)合作研發(fā)。中國的癌癥人群有其特殊性,有些癌癥在國外較少見,而中國有龐大的患者群體。例如中國有非常多的肝細(xì)胞瘤、鼻咽癌、食管癌患者。針對這類腫瘤的藥物研發(fā)中國醫(yī)生需要做大量工作。比如,在2015年ASCO會議上,來自中國的臨床研究“??颂婺岫€治療EGFR過表達或擴增的晚期食管癌的II期單臂試點試驗”在壁報專場展示,試驗結(jié)果良好。
Dr Lynch: It is good!
Lynch教授:試驗結(jié)果良好,真是太好了!