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    2015年ASCO年會(huì )于5月29日—6月2日在美國芝加哥召開(kāi)。5月31日上午的消化系統（非結直腸）腫瘤口頭報告專(zhuān)場(chǎng)上，一項摘要號為4001的試驗，在經(jīng)抗-PD-1單克隆抗體pembrolizumab（MK-3475）治療的，晚期胃癌患者中，評估了PD-L1表達和臨床預后之間的關(guān)系。整理如下：

    腫瘤利用PD-1通路逃避免疫監視。pembrolizumab是一種抗PD-1單克隆抗體，在晚期腫瘤中已經(jīng)顯示出抗腫瘤活性。研究人員通過(guò)Keynote-012試驗，對pembrolizumab治療晚期胃癌的安全性和有效性進(jìn)行評估。

    這項研究采用標準免疫組化方法（IHC）通過(guò)22C3抗體對來(lái)自于亞太（AP）和世界其他地區（ROW）保存的復發(fā)/晚期胃或胃食管交接區腺癌患者的腫瘤標本篩選PD-L1的表達。研究納入了基質(zhì)鮮明或癌細胞巢PD-L1染色≥1%的患者。Pembrolizumab的給藥方案為10mg/kg,每2周重復，持續用藥24個(gè)月或直至出現完全緩解，疾病進(jìn)展或無(wú)法耐受的毒副反應。每8周進(jìn)行影像學(xué)檢查。

    該研究主要療效終點(diǎn)是客觀(guān)反應率（ORR），該研究采用RECIST1.1標準，評定結果經(jīng)***中心復審。次要終點(diǎn)包括療效持續時(shí)間，無(wú)病生存期（PFS）和總生存期（OS）。

    在162例篩選患者中，有65（40%）為PD-L1+.這65例患者中，有39例納入了研究（AP 19例，ROW 20例，中位年齡63歲[范圍，33-78]）。晚期患者既往接受的療程數為0至5不等；其中2個(gè)療程治療以上的患者占67%.中位隨訪(fǎng)時(shí)間為8.8個(gè)月（6.2-12.6），其中13名（33%）患者仍在治療中。

    在試驗過(guò)程中，有四例患者發(fā)生3-5級（最高等級為5級）藥物相關(guān)不良反應，具體為周?chē)杏X(jué)神經(jīng)病變，乏力，食欲下降，缺氧，肺炎（各1例）。藥物相關(guān)性死亡（缺氧）1例。中心復查結果ORR為22%（95%CI,10-39），研究者評定結果ORR為33%（95%CI,19-50）。中位時(shí)間起效時(shí)間為8周（范圍7-16），中位療效持續時(shí)間為24周（范圍8+至33+）。PD-L1的表達水平與ORR相關(guān)（單側P=0.10）。6個(gè)月的PFS率為24%.6個(gè)月的OS率為69%.

    綜上所述，本項研究發(fā)現pembrolizumab在晚期胃癌中表現出可觀(guān)的抗腫瘤活性和可處理的治療相關(guān)毒副反應。這些結果為pembrolizumab治療胃癌研究的進(jìn)一步開(kāi)展提供了支持。臨床試驗信息：NCT01848834.

    閱讀原文摘要

    Relationship between PD-L1 expression and clinical outcomes in patients with advanced gastric cancer treated with the anti-PD-1 monoclonal antibody pembrolizumab （MK-3475） in KEYNOTE-012.（Abstract 4001）Authors:Yung-Jue Bang, Hyun-Choel Chung,et al.

    Session Type:Oral Abstract Session

    Background:Tumors use the PD-1 pathway to evade immune surveillance. Pembrolizumab, an anti–PD-1 monoclonal antibody, has shown antitumor activity in advanced cancers. We assessed the safety and efficacy of pembrolizumab in patients with advanced gastric cancer in KEYNOTE-012 （Clinicaltrials.gov identifier, NCT01848834）。

    Methods:Archival tumor samples from patients from Asia-Pacific （AP） and rest of the world （ROW） with recurrent or metastatic adenocarcinoma of the stomach or gastroesophageal junction were screened for PD-L1 expression using a prototype IHC assay with the 22C3 antibody. Only patients with distinctive stromal or ≥ 1% tumor nest cell PD-L1 staining were eligible. Patients received pembrolizumab 10 mg/kg every 2 weeks for up to 24 months or until complete response, progression, or unacceptable toxicity. Imaging was performed every 8 weeks. Primary efficacy end point is ORR assessed per RECIST v1.1 by independent central review. Secondary end points include duration of response, PFS, and OS.

    Results:Of the 162 patients screened, 65 （40%） were PD-L1+. Of these 65 patients, 39 enrolled （19 from AP, 20 from ROW; median age, 63 years [range, 33-78]）。 The number of prior therapies for advanced disease ranged from 0 to 5; 67% received ≥ 2 prior therapies. Median follow-up duration was 8.8 months （range, 6.2-12.6）； 13 patients （33%） remain on therapy. Four patients experienced 5 total grade 3-5 drug-related adverse events: pe**heral sensory neuropathy, fatigue, decreased appetite, hypoxia, and pneumonitis （n = 1 each）。 There was 1 drug-related death （hypoxia）。 ORR was 22% （95% CI, 10-39） by central review and 33% （95% CI, 19-50） by investigator review. Median time to response was 8 weeks （range, 7-16）， with a median response duration of 24 weeks （range, 8+ to 33+）。 PD-L1 expression level was associated with ORR （1-sided P = 0.10）。 The 6-month PFS rate was 24%. The 6-month OS rate was 69%.

    Conclusions:Pembrolizumab demonstrated manageable toxicity and promising antitumor activity in advanced gastric cancer. These results support the ongoing development of pembrolizumab for gastric cancer. Clinical trial ***rmation: NCT01848834.