Lessons learned: The safety profile in the patient groups who received FOLFIRI and simtuzumab did not differ from that in the FOLFIRI and placebo group.The addition of simtuzumab to chemotherapy with FOLFIRI does not improve clinical outcomes in patients with metastatic KRAS mutant colorectal carcinoma.
Background: Simtuzumab, a humanized IgG4 monoclonal antibody to lysyl oxidase-like 2 (LOXL2), blocks desmoplastic reaction in colorectal carcinoma (CRC) cells in vitro.
Methods: Patients with metastatic Kirsten rat sarcoma viral oncogene homolog (KRAS) mutant CRC were randomized to receive second-line 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) with either 200 or 700 mg simtuzumab or placebo every 2 weeks in cycles of 28 days. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety were assessed.
Results: In total, 249 patients were randomized and treated with FOLFIRI/simtuzumab 700 mg (n = 84), FOLFIRI/simtuzumab 200 mg (n = 85), and FOLFIRI/placebo (n = 80). After a median follow-up of 5.1, 3.8, and 5.5 months, respectively, median PFS for each of the respective treatment groups was 5.5 months (adjusted HR [95% CI], p value versus placebo; 1.32 [0.92, 1.89]; p = .10), 5.4 months (1.45 [1.01, 2.06]; p = .04), and 5.8 months. Median OS was 11.4 months (1.23 [0.80, 1.91]; p = .25), 10.5 months (1.50 [0.98, 2.30]; p = .06), and 16.3 months, respectively. ORR was 11.9%, 5.9%, and 10%, respectively. Simtuzumab was tolerable in metastatic KRAS mutant CRC patients.
Conclusion: The addition of simtuzumab to FOLFIRI did not improve clinical outcomes in patients with metastatic KRAS mutant CRC. The Oncologist 2017;22:243-e8.
经验总结
• FOLFIRI+Simtuzumab组患者的安全性特征与FOLFIRI+安慰剂组没有差异。
• Simtuzumab联合FOLFIRI化疗未改善转移性KRAS突变结直肠癌患者的临床预后。
摘要
背景. Simtuzumab是赖氨酰氧化酶样蛋白‐2（LOXL2）的一种人源化IgG4单克隆抗体, 在体外可阻止结直肠癌（CRC）细胞发生促结缔组织增生性反应
方法. 携带KRAS（Kirsten大鼠肉瘤病毒癌基因同源物）突变的转移性CRC患者随机接受5‐氟尿嘧啶、甲酰四氢叶酸和伊立替康（FOLFIRI）二线治疗联合Simtuzumab 200或700 mg或者联合安慰剂治疗, 每2周给药一次, 28天为一个周期。评估无进展生存期（PFS）、总生存期（OS）、客观缓解率（ORR）和安全性
结果. 总计249例患者随机接受FOLFIRI/Simtuzumab 700 mg（n=84）、FOLFIRI/Simtuzumab 200 mg（n=85）或FOLFIRI/安慰剂（n=80）治疗。分别进行为期5.1个月、3.8个月和5.5个月的中位随访后, 相应治疗组的中位PFS分别为5.5个月[校正HR（95% CI）, 与安慰剂比较的p值：1.32（0.92, 1.89）, p=0.10]、5.4个月[1.45（1.01, 2.06）, p=0.04]和5.8个月。中位OS分别为11.4个月[1.23（0.80, 1.91）, p=0.25]、10.5个月[1.50（0.98, 2.30）, p=0.06]和16.3个月。ORR分别为11.9%、5.9%和10%。转移性KRAS突变CRC患者可以耐受Simtuzumab
结论. Simtuzumab与FOLFIRI联用未改善转移性KRAS突变CRC患者的临床预后。
Trial registration: ClinicalTrials.gov NCT01479465.
© AlphaMed Press; the data published online to support this summary is the property of the authors.