Details

Autor(en) / Beteiligte

• Benson, Al B.
• Wainberg, Zev A.
• Hecht, J. Randolph
• Vyushkov, Dmitry
• Dong, Hua
• Bendell, Johanna
• Kudrik, Fred

Titel

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

Ist Teil von

• The oncologist (Dayton, Ohio), 2017-03, Vol.22 (3), p.241-e15

Ort / Verlag

England: AlphaMed Press

Erscheinungsjahr

2017

Link zum Volltext

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• Lessons Learned 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 Background The humanized IgG4 monoclonal antibody simtuzumab inhibits the extracellular matrix‐remodeling enzyme lysyl oxidase‐like 2 maintaining pathological stroma in tumors. Methods 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. Results 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. Conclusion The addition of simtuzumab to gemcitabine did not improve clinical outcomes in patients with mPaCa. 经验总结 • 吉西他滨/Simtuzumab组的安全性特征与吉西他滨/安慰剂组相似。 • Simtuzumab与吉西他滨联用未改善转移性胰腺腺癌患者的临床预后。 摘要 背景. 人源化IgG4单克隆抗体Simtuzumab可抑制赖氨酰氧化酶样蛋白‐2这一细胞外基质重塑酶, 该酶负责维系肿瘤的病理性基质。 方法. 转移性胰腺腺癌 (mPaCa) 成年患者随机接受静脉注射用吉西他滨 1,000mg/m2 联合 Simtuzumab 200 或 700mg 或者联合安慰剂治疗。主要终点为无进展生存期 (PFS), 次要终点包括总生存期 (OS)、客观缓解率 (ORR) 和安全性。 结果. 240例患者中有80例随机分配至吉西他滨/Simtuzumab 700 mg组, 79例分配至吉西他滨/Simtuzumab 200 mg组, 81例分配至吉西他滨/安慰剂组。分别对吉西他滨/Simtuzumab 700 mg组、吉西他滨/Simtuzumab 200 mg组和吉西他滨/安慰剂组进行为期3.0个月、1.9个月和3.4个月的中位随访后, 三组的中位PFS依次为3.7个月[校正风险比 (HR), 95%置信区间 (CI), 与安慰剂比较的p值：1.09 (0.74‐1.61); p = 0.73]、3.5个月 [1.13 (0.76‐1.66); p = 0.61] 和 3.7个月。中位OS分别为7.6个月[0.83 (0.57‐1.22); p = 0.28]、5.9 个月 [1.07 (0.73‐1.55); p = 0.69] 和5.7个月。ORR分别为13.9%、14.5%和23.5%。Simtuzumab耐受性良好。 结论. Simtuzumab与吉西他滨联用未改善mPaCa患者的临床预后。