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欧盟批准拜耳Stivarga用于胃肠道间质瘤(GIST)新适应症

来源:生物谷 2014-07-31 14:38

2014年7月31日讯 /生物谷BIOON/ --拜耳(Bayer)7月30日宣布,抗癌药Stivarga(regorafenib)获欧盟委员会(EC)批准,用于既往经2种酪氨酸激酶抑制剂【格列卫(Gleevec,通用名:imatinib,伊马替尼),索坦(Sutent,通用名:sunitinib,舒尼替尼)】治疗后病情恶化或不耐受的不可切除性或转移性胃肠道间质瘤(GIST)患者的治疗。此前,Stivarga已于2013年8月获欧盟批准用于转移性结直肠癌(mCRC)的治疗。

Stivarga GIST新适应症的获批,是基于关键III期GRID研究的数据。数据显示,与安慰剂+最佳支持疗法(BSC)相比,Stivarga+BSC组合疗法使无进展生存期(PFS)取得了统计学意义的显著改善(4.8个月 vs 0.9个月,p<0.0001)。

目前,Stivarga已获美国、欧盟、日本批准,用于转移性结直肠癌(mCRC)的治疗。同时,该药已获美国和日本批准用于治疗胃肠道间质瘤(GIST)。Stivarga是FDA批准的第三个治疗胃肠道间质瘤(GIST)的药物,另2个药物为诺华的格列卫(Gleevec)、辉瑞的索坦(Sutent)。

胃肠道间质瘤(GIST)是癌细胞发生在胃肠道的一种肿瘤,患者多为老年人。GIST,由于其极具侵略性的特点,目前依然是尚未满足的医疗需求,同时治疗的选择也很有限,相关临床研究数据表明,Stivarga有望为那些经标准治疗后复发的患者提供一种重要的治疗方案。

Stivarga是一种口服多激酶抑制剂,在临床前研究中,regorafenib能够抑制数个促血管生成VEGF受体酪氨酸激酶,这些激酶在肿瘤的血管生成中发挥着重要作用。该药还可以抑制癌和肿瘤微环境中的多种激酶,包括VEGFR 1-3, KIT, RET, PDGFR及FGFR。Stivarga由拜耳开发,由拜耳和Onyx制药联合推广。(生物谷Bioon.com)

英文原文:Stivarga® (regorafenib) from Bayer Approved in the European Union for the Treatment of Gastrointestinal Stromal Tumors

Approval in the second indication for Stivarga in the EU within one year / Decision based on positive results from Phase III GRID trial in which regorafenib significantly extended progression-free survival
Berlin, July 30, 2014 – The oncology compound Stivarga® (regorafenib) from Bayer has been approved by the European Commission (EC) for the treatment of adult patients with unresectable or metastatic gastrointestinal stromal tumors (GIST) who progressed on or are intolerant to prior treatment with imatinib and sunitinib. The approval of Stivarga in GIST is based on results from the pivotal Phase III study (GRID) that demonstrated a statistically significant improvement in progression-free survival (PFS) compared to placebo in patients with GIST whose disease had progressed after prior treatments. Stivarga is already approved in the EU for the treatment of patients with metastatic colorectal cancer (mCRC).

“Following the approval of Stivarga for GIST in several countries worldwide, including the U.S. and Japan, we are delighted to offer patients in Europe a new option for treating this rare yet relentless cancer,” said Dr. Joerg Moeller, Member of the Bayer HealthCare Executive Committee and Head of Global Development. “At Bayer, we are dedicated to exploring solutions for different tumor types and drive innovation to meet the unmet needs of both physicans and patients.”

“GIST is a highly aggressive cancer that can go undetected for years and, at the point of diagnosis, most patients have already progressed to advanced stages of disease. Survival rates are low and treatments are limited after imatinib and sunitinib,” said Jean Yves-Blay, GRID investigator, Professor of Medicine in Medical Oncology and Head of the Medical Oncology Department, Centre Leon Berard at Université Claude Bernard in Lyon, France. “The Phase III GRID trial demonstrated that progression-free survival with regorafenib is more than five times than with placebo, a significant improvement for those who have progressive disease.”

“One of the hardest things to hear from your doctor is that there is no treatment left for your disease,” said Markus Wartenberg, Member of the Board of Directors of the Sarcoma Patients EuroNet Association (SPAEN). “In rare cancers such as GIST, hope empowers people to continue fighting the cancer. New treatment options are welcomed so that patients can continue to defy their illness.”

The results of the pivotal Phase III GRID study showed that regorafenib plus best supportive care (BSC) significantly improved progression-free survival (PFS) compared to placebo plus BSC (HR=0.268 [95% CI 0.185-0.388], p<0.0001) in patients with metastatic and/or unresectable GIST who were previously treated with imatinib and sunitinib, reducing the risk of progression or death by 73%. The median PFS was 4.8 months in the regorafenib arm versus 0.9 months in the placebo arm (p<0.0001). The increase in PFS was consistent and independent of patient age, sex, geographic region, prior lines of treatment or ECOG performance status.

In clinical trials, the most frequently reported drug-related adverse events in regorafenib-treated patients versus placebo-treated patients, respectively, were: asthenia/fatigue, hand-foot skin reaction (HFSR) / palmar-plantar erythrodysesthesia (PPE), diarrhea, decreased appetite and food intake, hypertension, mucositis, dysphonia, infection, pain (not otherwise specified), decreased weight, gastrointestinal and abdominal pain, rash, fever and nausea. The most serious adverse drug reactions in patients receiving regorafenib are hepatotoxicity, hemorrhage, and gastrointestinal perforation. Adverse events in regorafenib-treated patients generally occur early (within the first two treatment cycles), therefore it is advised to monitor patients closely.

Full results from the GRID study were presented at the 48th Annual Meeting of the American Society of Clinical Oncology (ASCO) in June 2012 and published in November 2012 in The Lancet.

Regorafenib has been approved under the brand name Stivarga® in several countries, including the U.S. and Japan, for the treatment of GIST. In 60 countries worldwide, including the U.S., Europe and Japan, the product has also been approved for the treatment of patients with metastatic colorectal cancer (mCRC).

About the GRID Study
GRID (GIST – Regorafenib In Progressive Disease) was a randomized, double-blind, placebo-controlled, multi-center Phase III study of regorafenib for the treatment of GIST. It randomized 199 patients whose disease had progressed despite prior treatment with imatinib and sunitinib.

Patients were randomized in a 2:1 ratio to receive either regorafenib plus BSC or placebo plus BSC to evaluate efficacy and safety. Treatment cycles consisted of 160 mg regorafenib (or matching placebo) once daily for three weeks on / one week off plus BSC. The primary endpoint was PFS, and secondary endpoints included OS, time to progression, disease control rate, tumor response rate, and duration of response. The safety and tolerability of the two treatment groups were also compared. Patients initially randomized to placebo were allowed to cross over to open-label regorafenib once the disease progressed.

About Gastrointestinal Stromal Tumors (GIST)
GIST is the most common form of sarcoma arising from the muscle wall of the gastrointestinal tract. GIST represents a life-threatening malignancy if the disease has spread to other parts of the body (metastasized) or is unable to be surgically removed with curative intent. GIST affects an estimated 11-20 patients per million per year worldwide.

The discovery of oncogenic KIT kinase mutations in GISTs and the introduction of kinase inhibitor therapies have led to a rapid evolution in the understanding of these tumors. It is now established that 70–80% of GISTs harbor a KIT gene mutation, that these mutations lead to the continued activation of the kinase and that mutant KIT is a clinically important therapeutic target in GIST.

About Stivarga® (Regorafenib)
Stivarga® (regorafenib) is an oral multi-kinase inhibitor that inhibits various kinases within the mechanisms involved in tumor growth and progression – angiogenesis, oncogenesis and the tumor microenvironment. In preclinical studies, Stivarga inhibits several angiogenic VEGF receptor tyrosine kinases that play a role in tumor neoangiogenesis (the growth of new blood vessels). In addition to VEGFR 1-3 it also inhibits various oncogenic and tumor microenvironment kinases including TIE-2, RAF-1, BRAF, BRAFV600, KIT, RET, PDGFR, and FGFR, which individually and collectively impact upon tumor growth, formation of a stromal microenvironment and disease progression.

Stivarga is a compound developed by Bayer. In 2011, Bayer entered into an agreement with Onyx Pharmaceuticals, Inc., an Amgen subsidiary, under which Onyx receives a royalty on all global net sales of Stivarga in oncology.

About Oncology at Bayer
Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The oncology franchise at Bayer now includes three oncology products and several other compounds in various stages of clinical development. Together, these products reflect the company’s approach to research, which prioritizes targets and pathways with the potential to impact the way that cancer is treated.

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