Kensei Yamaguchi1,2, Kazumasa Fujitani3, Fumio Nagashima4, Yasushi Omuro5, Nozomu Machida6, Tomohiro Nishina7, Toshiko Koue8, Mika Tsujimoto8, Kaijiro Maeda8, Taroh Satoh9. 1. Saitama Cancer Center, Saitama, Japan. kensei.yamaguchi@jfcr.or.jp. 2. Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan. kensei.yamaguchi@jfcr.or.jp. 3. Osaka General Medical Center, Osaka, Japan. 4. Kyorin University Hospital, Mitaka, Japan. 5. Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan. 6. Shizuoka Cancer Center, Shizuoka, Japan. 7. National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan. 8. Eli Lilly Japan, Kobe, Japan. 9. Osaka University Hospital, Osaka, Japan.
Abstract
BACKGROUND: Ramucirumab, a monoclonal antibody vascular endothelial growth factor receptor-2 antagonist, given as monotherapy improved survival in a global phase 3 study (REGARD) of patients with gastric cancer. However, REGARD did not include Japanese patients. This study evaluated the efficacy and safety of ramucirumab monotherapy in Japanese patients with advanced gastric cancer. METHODS: This multicenter, open-label, nonrandomized phase 2 study (Clinicaltrials.gov: NCT01983878) was performed at 16 Japanese sites. Patients with advanced gastric or gastroesophageal junction cancer after disease progression following first-line chemotherapy received intravenous ramucirumab 8 mg/kg every 2 weeks. Primary efficacy outcome: 12-week progression-free survival rate (PFS). RESULTS: Thirty-six patients were enrolled. The 12-week PFS rate was 23.8% [90% confidence interval (CI) 12.4-37.2); the primary outcome was not met as the lower limit of the CI was outside the threshold of 16%. Median PFS was 6.6 weeks (90% CI 6.1-7.1). No patients achieved an objective response, and 11 (31%) patients achieved disease control. Median overall survival was 8.6 months (90% CI 5.7-10.7). The most frequent treatment-emergent adverse events (TEAEs) were diarrhea (9/36; 25%) and decreased appetite (8/36; 22%). Three patients reported Grade ≥ 3 ileus; all other Grade ≥ 3 TEAEs were reported by ≤ 2 patients. The most frequent adverse events of special interest (AESIs) were hypertension (10/36; 28%), bleeding/hemorrhage (7/36; 19%), and proteinuria (7/36; 19%). All Grade ≥ 3 AESIs were reported by ≤ 2 patients. CONCLUSIONS: These findings suggest that ramucirumab monotherapy has clinical activity and a manageable safety profile in Japanese patients with gastric cancer after disease progression following first-line chemotherapy.
BACKGROUND:Ramucirumab, a monoclonal antibody vascular endothelial growth factor receptor-2 antagonist, given as monotherapy improved survival in a global phase 3 study (REGARD) of patients with gastric cancer. However, REGARD did not include Japanese patients. This study evaluated the efficacy and safety of ramucirumab monotherapy in Japanese patients with advanced gastric cancer. METHODS: This multicenter, open-label, nonrandomized phase 2 study (Clinicaltrials.gov: NCT01983878) was performed at 16 Japanese sites. Patients with advanced gastric or gastroesophageal junction cancer after disease progression following first-line chemotherapy received intravenous ramucirumab 8 mg/kg every 2 weeks. Primary efficacy outcome: 12-week progression-free survival rate (PFS). RESULTS: Thirty-six patients were enrolled. The 12-week PFS rate was 23.8% [90% confidence interval (CI) 12.4-37.2); the primary outcome was not met as the lower limit of the CI was outside the threshold of 16%. Median PFS was 6.6 weeks (90% CI 6.1-7.1). No patients achieved an objective response, and 11 (31%) patients achieved disease control. Median overall survival was 8.6 months (90% CI 5.7-10.7). The most frequent treatment-emergent adverse events (TEAEs) were diarrhea (9/36; 25%) and decreased appetite (8/36; 22%). Three patients reported Grade ≥ 3 ileus; all other Grade ≥ 3 TEAEs were reported by ≤ 2 patients. The most frequent adverse events of special interest (AESIs) were hypertension (10/36; 28%), bleeding/hemorrhage (7/36; 19%), and proteinuria (7/36; 19%). All Grade ≥ 3 AESIs were reported by ≤ 2 patients. CONCLUSIONS: These findings suggest that ramucirumab monotherapy has clinical activity and a manageable safety profile in Japanese patients with gastric cancer after disease progression following first-line chemotherapy.
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