2015年ASCO年會于5月29日—6月2日在美國芝加哥召開。5月31日上午的消化系統（非結直腸）腫瘤口頭報告專場上，一項摘要號為4001的試驗，在經抗-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系。整理如下：

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

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

    該研究主要療效終點是客觀反應率（ORR），該研究采用RECIST1.1標準，評定結果經***中心復審。次要終點包括療效持續(xù)時間，無病生存期（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個療程治療以上的患者占67%.中位隨訪時間為8.8個月（6.2-12.6），其中13名（33%）患者仍在治療中。

    在試驗過程中，有四例患者發(fā)生3-5級（最高等級為5級）藥物相關不良反應，具體為周圍感覺神經病變，乏力，食欲下降，缺氧，肺炎（各1例）。藥物相關性死亡（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）。中位時間起效時間為8周（范圍7-16），中位療效持續(xù)時間為24周（范圍8+至33+）。PD-L1的表達水平與ORR相關（單側P=0.10）。6個月的PFS率為24%.6個月的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的抗腫瘤活性和可處理的治療相關毒副反應。這些結果為pembrolizumab治療胃癌研究的進一步開展提供了支持。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.