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首页 » 默克 » 默克爱必妥(Erbitux)结直肠癌试验FIRE-3中击败罗氏安维汀(Avastin)

默克爱必妥(Erbitux)结直肠癌试验FIRE-3中击败罗氏安维汀(Avastin)

来源:生物谷 2013-09-29 14:49

2013年9月29日讯 /生物谷BIOON/ --默克(Merck KGaA)9月28日宣布,德国肿瘤医学协会(AIO)公布了III期头对头(head-to-head)临床试验FIRE-3的新数据,该试验在转移性结直肠癌(mCRC)患者中开展,分别将默克爱必妥(Erbitux,通用名:cetuximab,西妥昔单抗)和罗氏安维汀(Avastin,通用名:bevacizumab,贝伐单抗)联合Folfiri化疗用于患者的一线治疗。新数据表明,在野生型RAS患者中,Erbitux+Folfiri治疗组平均总生存期比Avastin+Folfiri治疗组高7.5个月(33.1个月 vs 25.6个月,HR=0.70,p=0.011)。

在携带任意RAS突变(n=178)患者组中开展的一项析因分析(POst hoc analysis)表明,Erbitux+Folfiri治疗组平均总生存期为20.3个月,Avastin+Folfiri治疗组平均总生存期为20.6个月(HR: 1.09; p=0.60)。

这些数据继续巩固了Erbitux作为转移性结直肠癌一线治疗的价值,并指明RAS肿瘤状态有可能帮助鉴别出能够从Erbitux治疗中获得最大临床利益的患者群体。

结合近期其他相关研究的见解,这些数据表明,RAS野生型患者的一线治疗应包括抗EGFR疗法。

今年6月,默克公布的一项结直肠癌(mCRC)临床试验中,爱必妥(Erbitux)也击败了罗氏的安维汀(Avastin)。该项试验中所招募的患者,为肿瘤中仅含正常或野生型KRAS基因的结直肠癌患者,这类患者约占结直肠癌的60%,试验中分别将Erbitux和Avastin结合Folfiri化疗对患者进行了治疗。结果表明,Erbitux组平均存活时间比Avastin组长4个月(28.7个月 vs 25个月)。

目前,Erbitux和Avastin均已获批结合化疗作为转移性KRAS野生型肠癌患者的初始治疗。但6月份公布的临床试验结果,可能会使KRAS野生型患者群体转向Erbitux治疗。

默克正在对Erbitux的关键性试验CRYSTAL和OPUS试验,进行生物标志物分析,来帮助进一步阐明RAS突变在这些患者中的作用。

默克拥有Erbitux在北美以外国家和地区的销售及开发权利,百时美施贵宝(BMS)则拥有Erbitux在北美的销售权。

2012年,默克所取得的Erbitux销售额为8.87亿欧元(约合11.5亿美元),百时美施贵宝Erbitux的销售额为7.02亿美元。罗氏Avastin去年的销售额为57.6亿瑞士法郎(约合60亿美元)。(生物谷bioon.com)

英文原文:Merck KGaA's Drug Tops Roche's Avastin for Colon Cancer

HomenextMedianextNews Detail
Merck 's Erbitux Significantly Extends Survival by 7.5 Months in mCRC RAS Wild-Type Patients When Compared With Bevacizumab: New Analysis of FIRE-3 AIO Study

New data from a pre-planned analysis of the FIRE-3 study show an increase of median overall survival (OS) from 25.6 to 33.1 months (p=0.011) in mCRC patients with RAS wild-type tumors receiving first-line Erbitux plus FOLFIRI compared with patients receiving bevacizumab plus FOLFIRI.
In the group with any RAS mutations, patients who received Erbitux in first-line reached a median OS of 20.3 months vs. 20.6 months in the group that was treated with bevacizumab in first-line (p=0.60).

Darmstadt, Germany/Amsterdam, The Netherlands, September 28, 2013 – Merck today announced that the German cooperative investigator group AIO (Arbeitsgemeinschaft Internistische Onkologie) reported new data from the Phase III head-to-head clinical trial FIRE-3, which show a clinically relevant improvement from Erbitux® (cetuximab) plus FOLFIRI versus bevacizumab plus FOLFIRI as first-line treatment in metastatic colorectal cancer (mCRC) in patients with RAS wild-type tumors.1

The new data, from a preplanned exploratory analysis, were presented at the European Cancer Congress 2013 (ECCO-ESMO-ESTRO). The analysis shows a 7.5 month increase in median overall survival (OS) in mCRC patients with RAS wild-type tumors ((n=342); defined as having no mutations in exons 2, 3 and 4 of KRAS and NRAS), receiving first-line Erbitux plus FOLFIRI compared with patients receiving bevacizumab plus FOLFIRI (OS: 33.1 months vs. 25.6 months, respectively; hazard ratio [HR]: 0.70; p=0.011). In a post hoc analysis of the patient group with any RAS mutations (n=178), patients who received Erbitux plus FOLFIRI first-line reached an OS of 20.3 months vs. 20.6 months in the group that was treated with bevacizumab plus FOLFIRI (HR: 1.09; p=0.60).1
As previously presented at the annual meeting of the American Society of Clinical Oncology (ASCO) 2013 and at the World Congress on Gastrointestinal Cancer 2013, the primary endpoint of the trial, objective response rate based on investigators’ read in patients with KRAS exon 2 wild-type tumors, was not met.2,3 In the patient group with KRAS exon 2 wild-type tumors, an expected and balanced cross-over or continuation beyond progression with regard to subsequent biologic treatments in 2nd line therapy (either EGFR antibody or bevacizumab) was observed. Also, no major imbalances were noted with regard to chemotherapies used in 2nd line treatment. It is important to note that this result is not fully mature (57% event rate in the “intent-to-treat” KRAS exon 2 wild-type population) and will be updated in due course.2

“These new data from the Phase III study FIRE-3 show a 7.5-month increase in median overall survival to 33.1 months when using first-line Erbitux plus FOLFIRI as compared to using bevacizumab plus FOLFIRI in metastatic colorectal cancer. Such a prolongation is a paradigm shift in mCRC treatment since the introduction of monoclonal antibodies,” said Professor Volker Heinemann from the Ludwig-Maximilians University, Munich, and FIRE-3 principal investigator. “Together with insights from other recent relevant studies, these results suggest that first-line treatment of RAS wild-type patients should include an anti-EGFR therapy.”

“These results continue to reinforce the value of Erbitux as a first-line treatment for metastatic colorectal cancer and show that RAS tumor status is likely to help to identify those patients who are most likely to benefit from Erbitux,” said Dr. Annalisa Jenkins, Head of Global Drug Development and Medical at the Merck Serono division. “Additional biomarker analyses are being conducted on data from the pivotal Erbitux studies, CRYSTAL and OPUS to help shed additional light on the role of RAS mutations in these patients.”

About the FIRE-3 study
FIRE-3 is an independent, randomized, controlled, head-to-head Phase III trial led by Ludwig-Maximilians University in Munich, Germany. Merck Serono GmbH has financially supported the study. The FIRE-3 trial is being conducted in Europe, including 752 mCRC patients of whom 592 patients had confirmed KRAS exon 2 wild-type tumors. Of these, 297 patients were randomized to Erbitux plus FOLFIRI and 295 to bevacizumab plus FOLFIRI.2 113 patients had confirmed KRAS exon 2 mutations.

Initial data from the FIRE-3 study “intent-to-treat” population were presented at ASCO 2013. The primary endpoint, objective response rate (ORR) based on investigators’ read, of the FIRE-3 trial was not met (62% for Erbitux vs. 58% for bevacizumab; odds ratio 1.18).2

Analysis of RAS tumor status1
In the population with samples available for further RAS mutation analyses (n=407,KRAS exons 3 or 4, NRAS exons 2, 3, or 4), 84% of patients have RAS wild-type tumors and 16% RAS mutant tumors (other than KRAS exon 2).

Median OS was 33.1 months in mCRC patients with RAS wild-type tumors (n=342) receiving first-line Erbitux plus FOLFIRI compared with 25.6 months in patients receiving bevacizumab plus FOLFIRI (HR: 0.70; 95% confidence interval
[CI]: 0.53–0.92; p=0.011). ORR was substantially improved (65.5% for Erbitux plus FOLFIRI vs. 59.6% for bevacizumab plus FOLFIRI p=0.157). Progression-free survival (PFS) was similar in the two treatment groups (median PFS 10.4 months for Erbitux plus FOLFIRI vs. 10.2 months for bevacizumab plus FOLFIRI; HR: 0.93; 95% CI: 0.74–1.17; p=0.54).

In the group of patients with any RAS mutations (n=178), patients who received Erbitux plus FOLFIRI 1st line reached an OS of 20.3 months vs. 20.6 months in the group that was treated with bevacizumab plus FOLFIRI (HR=1.09; 95% CI: 0.78–1.52; p=0.60). For patients in the Erbitux plus FOLFIRI arm, median PFS was 7.5 months compared with 10.1 months in the bevacizumab plus FOLFIRI arm (HR=1.31; 95% CI: 0.98–1.78; p=0.085), and ORR was 38.0% vs. 51.2% (p=0.097), respectively.

No new safety concerns were reported in the trial in either treatment arm and toxicity profiles were as expected and manageable for both combinations.

About Colorectal Cancer
Colorectal cancer (CRC) is the fourth most common cancer worldwide, with an estimated incidence of more than 1.2 million cases globally.4 An estimated 608,000 deaths from CRC occur worldwide each year, accounting for 8% of all cancer deaths and making it the fourth most common cause of death from cancer.4 Almost 60% of the cases occur in developed regions, and incidence and mortality rates are substantially higher in menthan in women.5 In Europe alone, an estimated 436,000 people develop CRC every year, with approximately 212,000 people dying from the disease annually.

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