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ASCO 重磅LBA研究惹争议,肿瘤治疗“越多越好”还是“少即是多”?
作者:肿瘤瞭望 时间:2018/7/18 16:16:40    加入收藏
 关键字:LBA研究 
编者按:每年ASCO年会上的重磅LBA研究都会在肿瘤领域引起一阵热议,今年的几项LBA研究引起了一场关于肿瘤治疗的有趣辩论,到底是“越多越好”还是“越少越好”?下面,我们特邀纽约 Sloan-Kettering 癌症中心 (MSKCC) 胃肠道肿瘤学教授Andrew Epstein 博士分享他的主要观点。
 
“越多越好”——术前新辅助放化疗可以延长胰腺癌患者的OS
 
荷兰的Geertjan Van Tienhoven在ASCO 2018报告了胰腺癌PREOPANC-1试验的结果(LBA4002),主要是研究未转移或者可切除胰腺癌患者,特别是(交界性)可切除患者,术前新辅助治疗是否会带来额外的获益。
 
研究共纳入了246例患者,随机分配至先行手术(A组)或术前新辅助放化疗后手术(B组),两组均序贯辅助化疗,其中A组和B组分别有127例和119例。结果显示,B组患者的OS显著优于A组,A组和B组的mOS分别为13.5 vs 17.1个月,HR 0.71;P=0.047。两组的R0切除率也存在显著统计学差异,分别为31% vs 65%,P<0.001。这项研究初步结果表明,术前给予放化疗能带来额外的获益,当然我们还需要从这个试验中获取更多信息以指导这种难治性疾病的临床治疗。
 
对于这项研究,我们不仅需要关注显示具有统计学意义的最终试验结果,还需要了解试验中不同亚组的结果,特别是可切除和交界性可切除胰腺癌患者。对于可切除胰腺癌,正如Conroy等人观察到的那样,FOLFIRINOX方案与之前单独使用吉西他滨标准治疗相比,具有更好的总生存获益。但对于交界性可切除患者,还需要更多来自该试验的具有统计学意义的数据来验证没有联合放疗的单独化疗的作用。对于胰腺癌这样的全身性疾病,单独化疗可能具有与放疗相同的优点,且毒副反应更轻。
 
“少即是多”——高温腹腔化疗并不能给晚期结直肠癌患者带来获益
 
然而并不是所有的肿瘤治疗,都是越多越好。也有学者提出“少即是多”,更少过度治疗,反而有更好的生活质量,也不会增加复发风险。
 
法国Montpellier癌症中心 Francois Quenet教授在ASCO年会上汇报了一项评估在减瘤手术后联合腹腔热灌注化疗治疗腹膜种植转移癌(PC)患者疗效的临床研究(LBA3505),是“少即是多”又一典型案例。
 
过去10年,对选择性的可以进行肉眼完全切除的结直肠癌起源的腹膜种植转移癌(PC)患者,采用减瘤手术联合腹腔热灌注化疗显示出有前景的治疗效果。在PRODIGE 7研究中,肿瘤扩散到腹膜的结直肠癌患者被随机分配接受单独手术或HIPEC(腹腔热灌注化疗)联合手术。这项研究结果表明,很多结直肠癌腹膜转移患者联合HIPEC不会带来额外的获益,事实上,它还增加了副反应,在60天时可观察到接受腹腔热灌注化疗的患者术后并发症发生率更高。这一研究研究结果提示很多结直肠癌患者可以免于不必要的,且经常合并严重副作用的化疗。这些临床试验数据有助于临床医生为患者及其家属提供最佳治疗策略。
 
今年的ASCO上,还有很多研究体现了“少就是多”的治疗理念,例如 TAILORx研究表明,很多中复发风险的早期乳腺癌患者给予细胞毒化疗会带来不利影响。此外,在TKI治疗时代,转移性肾细胞癌的实践标准已经发生了很大的改变,之前这类患者的标准治疗是给予根治性肾切除,而现在大多数转移性肾癌患者可以避免肾切除带来的死亡风险。
 
还有很多有趣的研究正在探索当中,究竟是“越多越好”还是“少就是多”?仁者见仁,智者见智,相信未来这种争议还会继续,无疑会给肿瘤的临床治疗带来一些有益的改变,让我们拭目以待!
 
Oncology Frontier: We have seen the PREOPANC-1 trial in pancreatic cancer from Geertjan Van Tienhoven, The Netherlands here at ASCO 2018. What are your thoughts on this trial?
 
Dr Epstein: This is an important trial looking at a subset of patients with pancreas cancer that has not metastasized. It looked at patients with either resectable pancreas tumors or borderline resectable tumors. Particularly with the borderline resectable patients, we need more studies like this to see if preoperative therapies are going to be of additional benefit. While we are awaiting final results from the final events this study was powered for, it is suggested that there might be benefit for the randomization towards chemoradiotherapy in addition to surgery. We need more information from this trial, but it is an important next step in this difficult-to-treat disease.

Oncology Frontier: Is it likely that the results of this study will become first-line evidence?
 
Dr Epstein: It is possible, but I do think we need more research before we call this first-line evidence. We not only need the final results of the trial showing statistical significance to show any merit at all, but we also need to see what the contributors are from the different populations in the trial, specifically the resectable patients and the borderline resectable patients. With the resectable patients, as we also saw with Conroy et al, if the tumor can be surgically removed, then FOLFIRINOX gives much more overall survival benefit compared to the previous standard of gemcitabine alone. So it still remains to be seen what can be done with resectable patients. But for borderline resectable patients, we would need more data that is statistically significant from this trial, as well as the role of chemotherapy alone without radiation. With a systemic disease like pancreas cancer, chemotherapy alone may have just as much, if not more, merit and less burden than radiation therapy adds.
 
Oncology Frontier: As an example of “less is more” in cancer therapy, Francois Quenet presented his findings on the benefit of heated chemotherapy in patients undergoing surgery for peritoneal carcinomatosis. What is your opinion of his findings?
 
Dr Epstein: I agree that it is an excellent example of “less is more”. It is a very important trial in the randomized setting evaluating the merits of something that has been done in the United States and elsewhere without any high level evidence outlining what is helpful and what is not. Patients with colorectal cancer who had a spread of their cancer to the peritoneum (which makes up a small subset of colorectal cancer) were randomized to receive surgery alone or surgery with the addition of HIPEC (heated intraperitoneal chemotherapy). The use of heated chemotherapy is based on non-randomized small series data that seems to indicate there might be benefit. This trial answered that question with a resounding no. It does not add additional benefit. In fact, it adds harm. We saw at 60 days there was a higher post-operative complication rate in the patients who received the additional chemotherapy. We no longer need to do heated intraperitoneal chemotherapy, or any intraperitoneal chemotherapy for colorectal cancer patients in the context of this clinical trial, because without this clinical trial data, we are not putting our best treatment strategies forward for patients and their families.
 
Oncology Frontier: What other areas of research are you interested in at this meeting?
 
Dr Epstein: There have been many findings at this year’s ASCO. Another couple in the theme of “less is more” were presented at the Plenary Session yesterday. The TAILORx study showed that we can spare thousands of women the detriments of cytotoxic chemotherapy in those patients with intermediate risk recurrence score resected early stage breast cancer. Additionally, in the age of modern therapy with TKIs, in renal cell cancer we have now changed the standard of practice for metastatic renal cell cancer. Previously, the standard was to surgically remove the kidney cancer in the metastatic setting, but now we can spare patients the morbidity and risks associated with nephrectomy. So there are a lot of interesting things being done. More needs to be done. But the “less is more” findings are sobering and helpful.

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