胰島素樣生長因子（IGF-1和IGF-2）與胰島素樣生長因子受體（IGF-1R）結(jié)合，能促進細胞增殖和存活,。Ganitumab是IgG1的單克隆抗體，能阻滯IgG1與IGF-1R結(jié)合,。本文的研究人員旨在確定在激素受體陽性的局部晚期乳腺癌患者中,，內(nèi)分泌治療方案中增加ganitumab的療效和安全性。來自英國Royal Derby醫(yī)院的John F R Robertson針對上述問題進行了研究,，他們的研究結(jié)果發(fā)表在Lancet Oncol 2月最新的在線期刊上,。
本研究在門診患者和住院患者中進行。研究納入的受試者為激素受體陽性的局部晚期或轉(zhuǎn)移的絕經(jīng)后乳腺癌患者,，她們曾經(jīng)接受過內(nèi)分泌治療,。上述患者按照2:1的比例隨機分為兩組，一組按照12 mg/kg體重的劑量靜脈給予ganitumab,，另一組靜脈應(yīng)用安慰劑,，兩組患者都同時接受氟維司群肌肉注射或每日一次口服25mg依西美坦，氟維司群劑量為第1天500mg,，第15天和第29天250mg,，每28天為一個療程?；颊?、研究人員、研究監(jiān)察員和研究資助者都不知道患者具體所接受的治療方案,。每8周評價一次患者對治療的反應(yīng),。本研究的主要終點是患者疾病無進展生存期，對研究結(jié)果采用意向治療分析法進行分析,，研究的次要終點是患者的總體生存率,。本研究在ClinicalTrials.gov進行注冊，注冊號為NCT00626106,。
研究者共對189名患者進行篩查,，其中156人被納入研究，ganitumab組106人,，安慰劑組50人,。在兩組間,，研究者并未發(fā)現(xiàn)疾病無進展中位生存期存在顯著差異，前者為3.9月而后者為5.7月,。然而,，研究者發(fā)現(xiàn)與安慰劑組的患者相比，ganitumab組患者的總體生存期更差,，HR為1.78,，兩組差異具有顯著統(tǒng)的計學(xué)意義。因為高血糖的存在,，兩組的不良反應(yīng)事件相似,。最常見的3級或以上不良反應(yīng)事件為中性粒細胞減少，ganitumab組106名患者中有6名發(fā)生上述事件（6%）,，在安慰劑組的49名患者中有則1人（2%）,。Ganitumab組中的106名患者中有12人（11%）出現(xiàn)高血糖，其中6人為3級或4級高血糖,，而在安慰劑組中沒有患者出現(xiàn)高血糖癥,。Ganitumab組中有27人（25%）出現(xiàn)嚴(yán)重不良反應(yīng)事件，而在安慰劑組中為9人（18%）,。
研究結(jié)果指出,，對曾經(jīng)接受內(nèi)分泌治療的激素受體陽性的局部晚期或轉(zhuǎn)移性乳腺癌患者而言，將ganitumab加入到治療方案中并不會改善臨床預(yù)后,。來自本研究的結(jié)果并不支持在上述患者中就ganitumab進行更深入的研究,。（生物谷Bioon.com）
doi: 10.1073/pnas.1212769110
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Ganitumab with either exemestane or fulvestrant for postmenopausal women with advanced, hormonereceptor-positive breast cancer: a randomised, controlled,double-blind, phase 2 trial
John F R Robertson, Jean-Marc Ferrero, Hugues Bourgeois, Hagen Kennecke, Richard H de Boer, William Jacot, Jesse McGreivy, Samuel Suzuki,Min Zhu, Ian McCaff ery, Elwyn Loh, Jennifer L Gansert, Peter A Kaufman
Background Insulin-like growth factors (IGF-1 and IGF-2) bind to the IGF-1 receptor (IGF-1R), increasing cell proliferation and survival. Ganitumab is a monoclonal IgG1 antibody that blocks IGF-1R. We tested the effi cacy and safety of adding ganitumab to endocrine treatment for patients with hormone-receptor-positive breast cancer.Methods We did this phase 2 trial in outpatient clinics and hospitals. We enrolled postmenopausal women with hormone-receptor-positive, locally advanced or metastatic breast cancer previously treated with endocrine treatment.They were randomly assigned (2:1) with a central randomisation schedule to receive intravenous ganitumab 12 mg per kg bodyweight or placebo in combination with open-label intramuscular fulvestrant (500 mg on day 1, then 250 mg on days 15, 29, and every 28 days) or oral exemestane (25 mg once daily) on a 28-day cycle. Patients,investigators, study monitors, and the sponsor staff were masked to treatment allocation. Response was assessed every 8 weeks. The primary endpoint was median progression-free survival in the intention-to-treat population. We analysed overall survival as one of our secondary endpoints.
