Phase II study of motesanib in Japanese patients with advanced gastrointestinal stromal tumors with prior exposure to imatinib mesylate.
OBJECTIVE
Motesanib (AMG 706) is a multitargeted anticancer agent with an inhibitory action on the human vascular endothelial growth factor receptor, the platelet-derived growth factor receptor, and the cellular stem-cell factor receptor (KIT). The aim of this single-arm phase II clinical study was to assess the efficacy and safety of single-agent motesanib in Japanese patients with advanced gastrointestinal stromal tumors with prior exposure to imatinib mesylate.


METHODS
All patients had experienced progression or relapse while undergoing with imatinib as 400 mg/day or higher. The patients were administered 125 mg of motesanib once daily. The primary endpoint was overall response. Efficacy was evaluated according to the Response Evaluation Criteria in Solid Tumor, and safety was assessed according to the Common Terminology Criteria for Adverse Events (version 3).


RESULTS
Of 35 enrolled and treated patients, no patient showed a complete response, and one patient showed a partial response (PR). Seven had stable disease (SD) for at least 24 months, two of whom continued to have SD for more than 2 years. The median progression-free survival time was 16.1 weeks. Motesanib was well tolerated; commonly reported treatment-related adverse events were hypertension, diarrhea, and fatigue. Anemia was the only hematological toxicity that was reported.


CONCLUSIONS
One patient showed PR, and seven patients showed SD more than 24 weeks. Motesanib was found to be safe and well tolerated. The observed toxicities were consistent with Phase I study findings.
Sawaki
Akira
A
Department of Gastroenterology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi 464-8681, Japan. asawaki@aichi-cc.jp
Yamada
Yasuhide
Y
Komatsu
Yoshito
Y
Kanda
Tatsuo
T
Doi
Toshihiko
T
Koseki
Masato
M
Baba
Hideo
H
Sun
Yu-Nien
YN
Murakami
Koji
K
Nishida
Toshirou
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D044466:Asian People; D001549:Benzamides; D019008:Drug Resistance, Neoplasm; D004361:Drug Tolerance; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000000981:diagnostic imaging / Q000188:drug therapy*; D006801:Humans; D000068877:Imatinib Mesylate; D007211:Indoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007564:Japan; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D009841:Oligonucleotides; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D011859:Radiography; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001549:Benzamides; D007211:Indoles; D009841:Oligonucleotides; D010879:Piperazines; D011743:Pyrimidines; D009536:Niacinamide; D000068877:Imatinib Mesylate; C519562:imetelstat
AJR Am J Roentgenol. 2004 Dec;183(6):1619-28
15547201
Lancet. 2006 Oct 14;368(9544):1329-38
17046465
J Clin Oncol. 2007 May 1;25(13):1760-4
17470866
Science. 2003 Jan 31;299(5607):708-10
12522257
J Clin Oncol. 2007 May 1;25(13):1753-9
17470865
J Clin Oncol. 2005 Aug 20;23(24):5795-804
16110036
Ann Surg. 2000 Jan;231(1):51-8
10636102
J Clin Oncol. 2007 Jun 10;25(17):2369-76
17557949
N Engl J Med. 2001 Apr 5;344(14):1052-6
11287975
Hum Pathol. 2002 May;33(5):466-77
12094371
N Engl J Med. 2002 Aug 15;347(7):472-80
12181401
Science. 1998 Jan 23;279(5350):577-80
9438854
Lancet. 2004 Sep 25-Oct 1;364(9440):1127-34
15451219