ASCO 2014年会：10年临床试验证实转移性结直肠癌治疗方案无显著差别

【汤森路透会议报道】ASCO 2014年会：10年临床试验证实转移性结直肠癌治疗方案无显著差别

2014-06-10 汤森路透生命科学与制药

                               
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内容来源：汤森路透

编译者：生命科学研究快报 陈成材

说明：译文后附英文原文，若翻译有不明之处，请参见英文原文。

美国临床肿瘤学会（ASCO）2014年会：10年临床试验证实转移性结直肠癌治疗方案无显著差别

第50届ASCO全体会议重点报告了旨在比较四种最常见的无KRAS基因突变的转移性结直肠癌（Metastatic colorectal cancer，CRC）患者采用一线方案（first-line regimens）的III期临床试验结果：试验失败。研究人员指出，该试验的失败正体现了药物靶向治疗疾病的实验方法存在障碍，然而这只是冰山一角，需要学习的东西还有很多。

在这项试验中，患者存活期中位数（Median survival）约为29个月，不管使用哪种化疗方案：罗氏（Roche AG）的贝伐单抗（Bevacizumab）和化疗、礼来公司（Eli Lilly）的西妥昔单抗（Cetuximab）和化疗。而使用奥沙利铂（FOLFOX）或伊立替康（FOLFIRI）疗效也无多大差别。因此，无法确定哪种方案更好。

该临床试验选择了1 137例未接受治疗的转移性结直肠癌患者，并随机分配，或采用贝伐单抗联合化疗方案，或采用西妥昔单抗联合化疗方案，化疗方案则依据医师的建议，26.6%的患者选择奥沙利铂，剩余73.4%则选择伊立替康，患者跟踪治疗中位数为24个月。结果发现患者的总体生存期（OS）或无进展生存期（PFS）并无明显差异。使用贝伐单抗的患者组的OS和PFS分别为29和10.8个月。而使用妥昔单抗的患者组则分别为29.9和10.4个月。实验方案均无副作用发生。因两组患者OS都为29个月，因而其将会成为CRC临床试验新的参照标准。虽然有10%的患者生存期超过了5年，但该结果适用于某些实际情况而非学术上的理想情况。

这项临床试验持续10年，并采集了44 000个活体样本。研究人员认为在确定合适的试验对象时，或需要进一步进行分子水平的分析。同时，增加样本量也有助于发现治疗方案的区别，提高实验准确度。

英文原文

ASCO 2014: Pick your poison in CRC; pending bigger trials, they all look the same

CHICAGO – Like the late-stage adjuvant breast cancer study that failedbut brought big benefits, a phase III study comparing the four commonest,first-line regimens inmetastatic colorectal cancer （CRC） withoutKRAS mutations may have seemed a letdown at first.

But the trial, one of a handfulhighlighted during the plenary session of the 50th annual American Society ofClinical Oncology, set a new bar for experiments withdrugs targeting the disease, and yielded findings that represent “the tip ofthe iceberg of what we stand to learn,” said Alan Venook, physician at theUniversity of California-San Francisco, who presented the data.

In the study, median survivalwas about 29 months, no matter which approach was used: bevacizumab （Avastin,Roche AG）plus chemotherapy or cetuximab （Erbitux,Eli Lilly and Co.）plus chemo. The regimens FOLFOX （oxaliplatin/5-fluorouracil/leucovorin） orFOLFIRI （irinotecan/5-fluorouracil/leucovorin） bothturned out acceptable, too.

“We had no knowledge which onewould have been better,” said Venook. “This was essentially looking for adifference in the treatment arms.” But the experiment found “no differencebetween these two therapies [bevacizumab and cetuximab] as a starting point forthese patients.”

Enrolling 1,137 patients withuntreated metastatic CRC, the study funded by the National Institutes of Healthrandomly assigned them to get bevacizumab plus chemo or cetuximab plus chemo.Selection of the chemo regimen was based on physician preference, with doctorsfor 26.6 percent of patients opting for FOLFIRI and 73.4 percent for FOLFOX.The median follow-up was 24 months.

Researchers found nosignificant differences in either overall survival （OS） orprogression-free survival （PFS） betweenthe treatment groups. In the bevacizumab plus chemo arm, OS and PFS totaled 29months and 10.8 months, respectively. In the cetuximab plus chemo arm, thenumbers were 29.9 months and 10.4 months respectively.

No new treatment side effectsturned up. The OS of 29 months in both arms sets a “new benchmark” for CRCtrials, with 10 percent of patients in the study living beyond five years,Venook said, and “results apply in a variety of practice settings, not justacademic settings.” Importantly, the study “clarifies the standard of care” and“answers a question that industry might not ask,” since the answers could goagainst the interests of drug makers, he said.

The study lasted 10 years,involving 14 amendments and 11 interim analyses,” We took as long as was necessaryto get the answer,” Venook said. Some 44,000 biospecimens were collected, yetto be fully analyzed. “We hope that this can inform future studies,” he said.

Meanwhile, what’s a clinicianto do, when choosing a regimen in CRC? “Flipping a coin is not optimal,” Venooksaid, in response to an audience member’s question. “Further molecular analysismay be clearer about identifying patients who are the proper candidates.Expanded RAS analyses might inform us. We’re in the process of doing theanalysis and we don’t have those results yet.”

The choice of chemo regimen is“very much market-driven in the U.S. Seventy-five percent of patients willreceive FOLFOX, based on habit as much as anything else. I hope this studymight raise the possibility of FOLFIRI,” Venook said, though toxicity has mostto do with selection. “Cetuximab, frankly, causes a severe skin rash in manypatients, and that would be something that should be considered as well.”

Findings of theexperiment point to the need for larger trials, which could yield moreprecision and show plainer differences between treatment choices. “This is verymuch good to have these options,” Venook said. “As we evolve and get morebiomarkers, for example, I hope we’ll be more clear on what the right thing to dois.”

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