Hideaki Bando1, Hideki Shimodaira2, Kazumasa Fujitani3, Atsuo Takashima4, Kensei Yamaguchi5, Norisuke Nakayama6, Takehiro Takahashi7, Eiji Oki8, Mizutomo Azuma9, Tomohiro Nishina10, Shuichi Hironaka11, Yoshito Komatsu12, Kohei Shitara13. 1. Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan. 2. Department of Clinical Oncology, Tohoku University Hospital, Sendai, Japan. 3. Department of Surgery, Osaka General Medical Center, Osaka, Japan. 4. Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan. 5. Department of Gastroenterological Chemotherapy, The Cancer Institute Hospital Japanese Foundation for Cancer Research, Tokyo, Japan. 6. Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, Japan. 7. Institute of Molecular Oncology, Showa University School of Medicine, Tokyo, Japan. 8. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 9. Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan. 10. Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan. 11. Clinical Trial Promotion Department, Chiba Cancer Center, Chiba, Japan. 12. Division of Cancer Chemotherapy, Hokkaido University Hospital, Sapporo, Japan. 13. Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan. Electronic address: kshitara@east.ncc.go.jp.
Abstract
BACKGROUND: Nanoparticle albumin-bound (nab)-paclitaxel was developed to improve paclitaxel solubility and does not need premedication to avoid infusion-related reactions associated with solvent-based (sb)-paclitaxel. We conducted a phase II trial to investigate the efficacy and safety of nab-paclitaxel plus ramucirumab combination therapy for previously treated advanced gastric cancer. PATIENTS AND METHODS: Patients with unresectable advanced gastric cancer refractory to first-line chemotherapy were administered nab-paclitaxel 100 mg/m2 intravenously on days 1, 8 and 15, plus ramucirumab 8 mg/kg intravenously on days 1 and 15 of a 28-day cycle. The primary end-point was Independent Review Committee (IRC)-assessed overall response rate (ORR). Secondary end-points were progression-free survival (PFS), overall survival (OS), disease control rate (DCR), safety and quality of life (QOL). RESULTS: Forty-five patients were enrolled; 43 received the study treatment. The ORR assessed by the IRC was 54.8% (90% confidence interval [CI] 41.0-68.0) and the primary end-point was met. The DCR was 92.9% (95% CI 80.5-98.5). The IRC-assessed median PFS was 7.6 months (95% CI 5.4-8.1). The median OS was not reached at the data cutoff. The main treatment-related grade 3 or 4 adverse events were decreased neutrophil count (76.7%), decreased white blood cell count (27.9%), anaemia (11.6%), decreased appetite (7.0%), febrile neutropenia (4.7%), hypertension (4.7%) and proteinuria (4.7%). No treatment-related deaths occurred. No QOL deterioration was observed during study treatment. CONCLUSION: Nab-paclitaxel plus ramucirumab combination therapy shows promising activity and manageable toxicities and could be a useful second-line treatment option for patients with previously treated advanced gastric cancer.
BACKGROUND: Nanoparticle albumin-bound (nab)-paclitaxel was developed to improve paclitaxel solubility and does not need premedication to avoid infusion-related reactions associated with solvent-based (sb)-paclitaxel. We conducted a phase II trial to investigate the efficacy and safety of nab-paclitaxel plus ramucirumab combination therapy for previously treated advanced gastric cancer. PATIENTS AND METHODS: Patients with unresectable advanced gastric cancer refractory to first-line chemotherapy were administered nab-paclitaxel 100 mg/m2 intravenously on days 1, 8 and 15, plus ramucirumab 8 mg/kg intravenously on days 1 and 15 of a 28-day cycle. The primary end-point was Independent Review Committee (IRC)-assessed overall response rate (ORR). Secondary end-points were progression-free survival (PFS), overall survival (OS), disease control rate (DCR), safety and quality of life (QOL). RESULTS: Forty-five patients were enrolled; 43 received the study treatment. The ORR assessed by the IRC was 54.8% (90% confidence interval [CI] 41.0-68.0) and the primary end-point was met. The DCR was 92.9% (95% CI 80.5-98.5). The IRC-assessed median PFS was 7.6 months (95% CI 5.4-8.1). The median OS was not reached at the data cutoff. The main treatment-related grade 3 or 4 adverse events were decreased neutrophil count (76.7%), decreased white blood cell count (27.9%), anaemia (11.6%), decreased appetite (7.0%), febrile neutropenia (4.7%), hypertension (4.7%) and proteinuria (4.7%). No treatment-related deaths occurred. No QOL deterioration was observed during study treatment. CONCLUSION:Nab-paclitaxel plus ramucirumab combination therapy shows promising activity and manageable toxicities and could be a useful second-line treatment option for patients with previously treated advanced gastric cancer.