Hecht J Randolph, Benson Al B, Vyushkov Dmitry, Yang Yingsi, Bendell Johanna, Verma Udit
David Geffen School of Medicine at the University of California, Los Angeles, California, USA
Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA.
Oncologist. 2017 Mar;22(3):243-e23. doi: 10.1634/theoncologist.2016-0479. Epub 2017 Feb 28.
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 mutant colorectal carcinoma.
Simtuzumab, a humanized IgG4 monoclonal antibody to lysyl oxidase-like 2 (LOXL2), blocks desmoplastic reaction in colorectal carcinoma (CRC) cells in vitro.
Patients with metastatic Kirsten rat sarcoma viral oncogene homolog () 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.
In total, 249 patients were randomized and treated with FOLFIRI/simtuzumab 700 mg ( = 84), FOLFIRI/simtuzumab 200 mg ( = 85), and FOLFIRI/placebo ( = 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], value versus placebo; 1.32 [0.92, 1.89]; = .10), 5.4 months (1.45 [1.01, 2.06]; = .04), and 5.8 months. Median OS was 11.4 months (1.23 [0.80, 1.91]; = .25), 10.5 months (1.50 [0.98, 2.30]; = .06), and 16.3 months, respectively. ORR was 11.9%, 5.9%, and 10%, respectively. Simtuzumab was tolerable in metastatic mutant CRC patients.
The addition of simtuzumab to FOLFIRI did not improve clinical outcomes in patients with metastatic mutant CRC. 2017;22:243-e8.
接受FOLFIRI和西马妥珠单抗治疗的患者组的安全性与接受FOLFIRI和安慰剂治疗的患者组并无差异。在FOLFIRI化疗方案中添加西马妥珠单抗并不能改善转移性KRAS突变型结直肠癌患者的临床结局。
西马妥珠单抗是一种针对赖氨酰氧化酶样2（LOXL2）的人源化IgG4单克隆抗体，可在体外阻断结直肠癌细胞中的促结缔组织增生反应。
将转移性 Kirsten 大鼠肉瘤病毒癌基因同源物（KRAS）突变型结直肠癌患者随机分为两组，分别接受二线5-氟尿嘧啶、亚叶酸钙和伊立替康（FOLFIRI）联合治疗，每2周一次，每次联合200mg或700mg西马妥珠单抗或安慰剂，每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。
总共249例患者被随机分组并接受FOLFIRI/700mg西马妥珠单抗（n = 84）、FOLFIRI/200mg西马妥珠单抗（n = 85）和FOLFIRI/安慰剂（n = 80）治疗。分别经过5.1、3.8和5.5个月的中位随访后，各治疗组的中位PFS分别为5.5个月（调整后HR [95% CI]，与安慰剂相比的值；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%。西马妥珠单抗在转移性KRAS突变型结直肠癌患者中耐受性良好。
在FOLFIRI方案中添加西马妥珠单抗并不能改善转移性KRAS突变型结直肠癌患者的临床结局。2017；22：243-e8。
