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 ABSTRACT: 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. The Oncologist 2017;22:241-e7.
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。
Trial registration: ClinicalTrials.gov NCT01472198.
© AlphaMed Press; the data published online to support this summary is the property of the authors.