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Phase II study of motesanib in Japanese patients with advanced gastrointestinal stromal tumors with prior exposure to imatinib mesylate.

Sawaki A, Yamada Y, Komatsu Y, Kanda T, Doi T, Koseki M, Baba H, Sun YN, Murakami K, Nishida T - Cancer Chemother. Pharmacol. (2009)

Bottom Line: Motesanib was well tolerated; commonly reported treatment-related adverse events were hypertension, diarrhea, and fatigue.Motesanib was found to be safe and well tolerated.The observed toxicities were consistent with Phase I study findings.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi 464-8681, Japan. asawaki@aichi-cc.jp

ABSTRACT

Purpose: 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.

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Related in: MedlinePlus

Kaplan–Meier estimates of PFS
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Fig2: Kaplan–Meier estimates of PFS

Mentions: The tumor response as assessed by an independent radiographic image reviewer is shown in Table 2. No CR was observed among the 35 patients enrolled in this study. One patient (3%; 95% CI 0.1–14.9%) had a PR and seven patients (20%) demonstrated SD for at least 24 months, two of whom continued to have SD for more than 2 years. Twelve additional patients had SD lasting for 12 weeks or more. Thirteen patients experienced disease progression within 12 weeks. The patient with PR had a gastric GIST with spindle-cell type, exon 11 mutation, liver, and peritoneal metastases, and had initially responded to imatinib with SD as assessed by RECIST (Fig. 1). The median PFS time of motesanib was 16.1 weeks (95% CI 8.4–32.0 weeks; Fig. 2).Table 2


Phase II study of motesanib in Japanese patients with advanced gastrointestinal stromal tumors with prior exposure to imatinib mesylate.

Sawaki A, Yamada Y, Komatsu Y, Kanda T, Doi T, Koseki M, Baba H, Sun YN, Murakami K, Nishida T - Cancer Chemother. Pharmacol. (2009)

Kaplan–Meier estimates of PFS
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2824121&req=5

Fig2: Kaplan–Meier estimates of PFS
Mentions: The tumor response as assessed by an independent radiographic image reviewer is shown in Table 2. No CR was observed among the 35 patients enrolled in this study. One patient (3%; 95% CI 0.1–14.9%) had a PR and seven patients (20%) demonstrated SD for at least 24 months, two of whom continued to have SD for more than 2 years. Twelve additional patients had SD lasting for 12 weeks or more. Thirteen patients experienced disease progression within 12 weeks. The patient with PR had a gastric GIST with spindle-cell type, exon 11 mutation, liver, and peritoneal metastases, and had initially responded to imatinib with SD as assessed by RECIST (Fig. 1). The median PFS time of motesanib was 16.1 weeks (95% CI 8.4–32.0 weeks; Fig. 2).Table 2

Bottom Line: Motesanib was well tolerated; commonly reported treatment-related adverse events were hypertension, diarrhea, and fatigue.Motesanib was found to be safe and well tolerated.The observed toxicities were consistent with Phase I study findings.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi 464-8681, Japan. asawaki@aichi-cc.jp

ABSTRACT

Purpose: 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.

Show MeSH
Related in: MedlinePlus