A Phase II Randomized, Double-Blind, Placebo-Controlled Study of Simtuzumab or Placebo in Combination with Gemcitabine for the First-Line Treatment of Pancreatic Adenocarcinoma.
A Phase II Randomized, Double-Blind, Placebo-Controlled Study of Simtuzumab or Placebo in Combination with Gemcitabine for the First-Line Treatment of Pancreatic Adenocarcinoma.
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DOI：
10.1634/theoncologist.2017-0024
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发表时间：
2017-03
期刊：
影响因子：
--
通讯作者：
Kudrik F
中科院分区：
文献类型：
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作者：
Benson AB 3rd;Wainberg ZA;Hecht JR;Vyushkov D;Dong H;Bendell J;Kudrik F
吉西他滨/辛妥珠单抗组的安全性与吉西他滨/安慰剂组相似。人源化IgG4单克隆抗体simtuzumab抑制细胞外基质重塑酶赖基氧化酶样2维持肿瘤病理间质。成年转移性胰腺腺癌（mPaCa）患者被随机分配接受静脉注射吉西他滨，1000 mg/m2，联合200或700 mg辛妥珠单抗或安慰剂。主要终点是无进展生存期（PFS），次要终点包括总生存期（OS）、客观缓解率（ORR）和安全性。在240例患者中，80例随机分配到吉西他滨/辛妥珠单抗700 mg组，79例吉西他滨/辛妥珠单抗200 mg组，81例吉西他滨/安慰剂组。吉西他滨/辛妥珠单抗700 mg、吉西他滨/辛妥珠单抗200 mg和吉西他滨/安慰剂组的中位随访时间分别为3.0、1.9和3.4个月，中位PFS为3.7个月(校正风险比[HR]， 95%可信区间[CI]， p值与安慰剂组比较：1.09 [0.74-1.61];p =。73)， 3.5个月(1.13 [0.76-1.66],p =。[61])和3.7个月。中位OS为7.6个月（0.83 [0.57-1.22]）；28)， 5.9个月(1.07 [0.73-1.55]；69个月，5.7个月。orr分别为13.9%、14.5%和23.5%。辛妥珠单抗耐受性良好。在吉西他滨的基础上加入辛妥珠单抗并没有改善mPaCa患者的临床结果。
The safety profile in the gemcitabine/simtuzumab group was similar to that in the gemcitabine/placebo group. The addition of simtuzumab to gemcitabine does not improve clinical outcomes in patients with metastatic pancreatic adenocarcinoma The humanized IgG4 monoclonal antibody simtuzumab inhibits the extracellular matrix‐remodeling enzyme lysyl oxidase‐like 2 maintaining pathological stroma in tumors. Adult patients with metastatic pancreatic adenocarcinoma (mPaCa) were randomly assigned to receive intravenous gemcitabine, 1,000 mg/m2, in combination with 200 or 700 mg simtuzumab or placebo. Primary endpoint was progression‐free survival (PFS), secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. Of 240 patients, 80 were randomly assigned to gemcitabine/simtuzumab 700 mg, 79 to gemcitabine/simtuzumab 200 mg, and 81 to gemcitabine/placebo. After a median follow‐up of 3.0, 1.9, and 3.4 months for gemcitabine/simtuzumab 700 mg, gemcitabine/simtuzumab 200 mg, and gemcitabine/placebo, respectively, the median PFS was 3.7 months (adjusted hazard ratio [HR], 95% confidence interval [CI], p value vs placebo: 1.09 [0.74–1.61]; p = .73), 3.5 months (1.13 [0.76–1.66], p = .61]), and 3.7 months, respectively. Median OS was 7.6 months (0.83 [0.57–1.22]; p = .28), 5.9 months (1.07 [0.73–1.55]; p = .69), and 5.7 months, respectively. ORRs were 13.9%, 14.5%, and 23.5%, respectively. Simtuzumab was well tolerated. The addition of simtuzumab to gemcitabine did not improve clinical outcomes in patients with mPaCa.