AMG386联合索拉菲尼在转移性肾透明细胞癌患者中的应用：一项随机、双盲、安慰剂对照、2期研究

AMG 386 in combination with sorafenib in patients with metastatic clear cell carcinoma of the kidney : A randomized, double-blind, placebo-controlled, phase 2 study

Abstract
BACKGROUND:
This study evaluated the tolerability and antitumor activity of AMG 386, a peptibody (a peptide Fc fusion) that neutralizes the interaction of angiopoietin-1 and angiopoietin-2 with Tie2 (tyrosine kinase with immunoglobulin-like and EGF-like domains 2), plus sorafenib in patients with clear cell metastatic renal cell carcinoma (mRCC) in a randomized controlled study.
METHODS:
Previously untreated patients with mRCC were randomized 1:1:1 to receive sorafenib 400 mg orally twice daily plus intravenous AMG 386 at 10 mg/kg (arm A) or 3 mg/kg (arm B) or placebo (arm C) once weekly (qw). Patients in arm C could receive open-label AMG 386 at 10 mg/kg qw plus sorafenib following disease progression. The primary endpoint was progression-free survival (PFS).
RESULTS:
A total of 152 patients were randomized. Median PFS was 9.0, 8.5, and 9.0 months in arms A, B, and C, respectively (hazard ratio for arms A and B vs arm C, 0.88; 95% confidence interval [CI], 0.60-1.30; P = .523). The objective response rate (95% CI) for arms A, B, and C, respectively, was 38% (25%-53%), 37% (24%-52%), and 25% (14%-40%). Among 30 patients in arm C who had disease progression and subsequently received open-label AMG 386 at 10 mg/kg qw, the objective response rate was 3% (95% CI, 0%-17%). Frequently occurring adverse events (AEs) included diarrhea (arms A/B/C, 70%/67%/56%), palmar-plantar erythrodysesthesia syndrome (52%/47%/54%), alopecia (50%/45%/50%), and hypertension (42%/49%/46%). Fifteen patients had grade 4 AEs (arms A/B/C, n = 3/7/5), of whom 4 had fatal AEs (n = 2/1/1), with 1 (abdominal pain, arm B) considered possibly related to AMG 386.

CONCLUSIONS:
In patients with mRCC, AMG 386 plus sorafenib was tolerable but did not significantly improve PFS compared with placebo plus sorafenib. Cancer 2012. © 2012 American Cancer Society.

原文链接：http://onlinelibrary.wiley.com/doi/10.1002/cncr.27632/abstract;jsessionid=64AA5B5A2CAB6D167A7253F224350AD7.d02t03