Daisuke Sakai1, Hiroya Taniguchi2, Naotoshi Sugimoto3, Takao Tamura4, Tomohiro Nishina5, Hiroki Hara6, Taito Esaki7, Tadamichi Denda8, Takeshi Sakamoto9, Hiroyuki Okuda10, Taroh Satoh11, Takahiro Tsushima12, Akitaka Makiyama13, Takashi Tsuda14, Ayumu Hosokawa15, Hidekazu Kuramochi16, Shinya Tokunaga17, Toshikazu Moriwaki18, Hisateru Yasui19, Hiroyasu Ishida20, Akihito Tsuji21, Satoshi Otsu22, Hozumi Shimokawa23, Eishi Baba24, Mikio Sato25, Shigemi Matsumoto26, Yukinori Ozaki27, Katsunori Shinozaki28, Hiroshi Tamagawa29, Masahiro Goto30, Shigenori Kadowaki2, Hirofumi Fujii31, Yasuhiro Koh32, Kentaro Yamazaki12, Shuichi Hironaka22, Junji Kishimoto33, Narikazu Boku34, Ichinosuke Hyodo18, Kei Muro2. 1. Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Suita, Japan. Electronic address: dsakai@cfs.med.osaka-u.ac.jp. 2. Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan. 3. Department of Medical Oncology, Osaka International Cancer Institute, Osaka, Japan. 4. Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan. 5. Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan. 6. Department of Gastroenterology, Saitama Cancer Center, Saitama, Japan. 7. Department of Gastrointestinal and Medical Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan. 8. Division of Gastroenterology, Chiba Cancer Center, Chiba, Japan. 9. Department of Gastroetererological Oncology, Hyogo Cancer Center, Akashi, Japan. 10. Department of Medical Oncology, Keiyukai Sapporo Hospital, Sapporo, Japan. 11. Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Suita, Japan. 12. Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan. 13. Department of Hematology/Oncology, Japan Community Healthcare Organization Kyushu Hospital, Fukuoka, Japan. 14. Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan. 15. Department of Gastroenterology and Hematology, Faculty of Medicine, University of Toyama, Toyama, Japan. 16. Department of Chemotherapy, Tokyo Women's Medical University, Yachiyo Medical Center, Yachiyo, Japan. 17. Department of Medical Oncology, Osaka City General Hospital, Osaka, Japan. 18. Division of Gastroenterology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan. 19. Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Japan. 20. Department of Gastroenterology, National Hospital Organization Mito Medical Center, Mito, Japan. 21. Department of Clinical Oncology, Kagawa University Faculty of Medicine, Kagawa, Japan. 22. Department of Medical Oncology and Hematology, Oita University Faculty of Medicine, Oita, Japan. 23. Department of Medical Oncology, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Japan. 24. Department of Oncology and Social Medicine, Graduate School of Medical Sciences, Kyushu University, Japan. 25. Department of Gastroenterology and Hepatology, Ryugasaki Saiseikai Hospital, Ryugasaki, Japan. 26. Department of Medical Oncology, Kyoto University Hospital, Kyoto, Japan. 27. Department of Medical Oncology, Toranomon Hospital, Tokyo, Japan. 28. Division of Clinical Oncology, Hiroshima Prefectural Hospital, Hiroshima, Japan. 29. Department of Surgery, Osaka General Medical Center, Osaka, Japan. 30. Cancer Chemotherapy Center, Osaka Medical College, Osaka, Japan. 31. Department of Clinical Oncology, Jichi Medical University Hospital, Tochigi, Japan. 32. Internal Medicine III, Wakayama Medical University, Wakayama, Japan. 33. Center for Clinical and Translational Research, Kyushu University Hospital, Japan. 34. Division of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
Abstract
BACKGROUND:Cetuximab has been shown to be clinically active when given in combination with irinotecan in patients with irinotecan-refractory metastatic colorectal cancer (mCRC). However, it has remained unclear whether panitumumab is effective when combined with irinotecan. We compared efficacies of both regimens in this randomised phase II study. PATIENTS AND METHODS: Patients with wild-type KRAS exon 2 mCRC previously treated withfluorouracil-, oxaliplatin- and irinotecan-based chemotherapies were randomised (1:1) to either panitumumab plus irinotecan (panitumumab arm) or cetuximab plus irinotecan (cetuximab arm). The primary end-point was progression-free survival (PFS). The planned sample size was 120, expecting a hazard ratio (HR) of 1.0 with non-inferiority margin of 1.3 (one-sided alpha error 0.2 and power 0.7). Major secondary end-points were overall survival (OS), response rate and safety. RESULTS:From December 2011 to September 2014, 121 patients were enrolled, and 61 and 59 patients were randomised to the panitumumab and cetuximab arms, respectively (1 patient excluded). Most patients (97%) had received prior chemotherapies containing bevacizumab. The median PFS was 5.42 months in the panitumumab arm and 4.27 months in the cetuximab arm (HR = 0.64, 95% confidence interval [CI] = 0.44-0.94, P < 0.001 for non-inferiority, P = 0.058 for superiority), and median OS was 14.85 and 11.53 months (HR = 0.66, 95% CI = 0.44-1.00, P = 0.050 for superiority), respectively. The incidence of grade 3 or 4 hypomagnesaemia was higher in the panitumumab arm than that in the cetuximab arm (17% vs. 7%). CONCLUSION:Panitumumab may be non-inferior to cetuximab in combination with irinotecan in survival of patients with irinotecan-refractory mCRC.
RCT Entities:
BACKGROUND:Cetuximab has been shown to be clinically active when given in combination with irinotecan in patients with irinotecan-refractory metastatic colorectal cancer (mCRC). However, it has remained unclear whether panitumumab is effective when combined with irinotecan. We compared efficacies of both regimens in this randomised phase II study. PATIENTS AND METHODS: Patients with wild-type KRAS exon 2 mCRC previously treated with fluorouracil-, oxaliplatin- and irinotecan-based chemotherapies were randomised (1:1) to either panitumumab plus irinotecan (panitumumab arm) or cetuximab plus irinotecan (cetuximab arm). The primary end-point was progression-free survival (PFS). The planned sample size was 120, expecting a hazard ratio (HR) of 1.0 with non-inferiority margin of 1.3 (one-sided alpha error 0.2 and power 0.7). Major secondary end-points were overall survival (OS), response rate and safety. RESULTS: From December 2011 to September 2014, 121 patients were enrolled, and 61 and 59 patients were randomised to the panitumumab and cetuximab arms, respectively (1 patient excluded). Most patients (97%) had received prior chemotherapies containing bevacizumab. The median PFS was 5.42 months in the panitumumab arm and 4.27 months in the cetuximab arm (HR = 0.64, 95% confidence interval [CI] = 0.44-0.94, P < 0.001 for non-inferiority, P = 0.058 for superiority), and median OS was 14.85 and 11.53 months (HR = 0.66, 95% CI = 0.44-1.00, P = 0.050 for superiority), respectively. The incidence of grade 3 or 4 hypomagnesaemia was higher in the panitumumab arm than that in the cetuximab arm (17% vs. 7%). CONCLUSION:Panitumumab may be non-inferior to cetuximab in combination with irinotecan in survival of patients with irinotecan-refractory mCRC.
Authors: Yeo Jin Choi; Chang-Young Choi; Sandy Jeong Rhie; Sooyoung Shin Journal: Int J Environ Res Public Health Date: 2022-07-27 Impact factor: 4.614