Randomised phase II study of panitumumab plus irinotecan versus cetuximab plus irinotecan in patients with KRAS wild-type metastatic colorectal cancer refractory to fluoropyrimidine, irinotecan and oxaliplatin (WJOG 6510G)

• Published in: European journal of cancer (1990) 2020-08, Vol.135, p.11-21
• Main Authors: Sakai, Daisuke, Taniguchi, Hiroya, Sugimoto, Naotoshi, Tamura, Takao, Nishina, Tomohiro, Hara, Hiroki, Esaki, Taito, Denda, Tadamichi, Sakamoto, Takeshi, Okuda, Hiroyuki, Satoh, Taroh, Tsushima, Takahiro, Makiyama, Akitaka, Tsuda, Takashi, Hosokawa, Ayumu, Kuramochi, Hidekazu, Tokunaga, Shinya, Moriwaki, Toshikazu, Yasui, Hisateru, Ishida, Hiroyasu, Tsuji, Akihito, Otsu, Satoshi, Shimokawa, Hozumi, Baba, Eishi, Sato, Mikio, Matsumoto, Shigemi, Ozaki, Yukinori, Shinozaki, Katsunori, Tamagawa, Hiroshi, Goto, Masahiro, Kadowaki, Shigenori, Fujii, Hirofumi, Koh, Yasuhiro, Yamazaki, Kentaro, Hironaka, Shuichi, Kishimoto, Junji, Boku, Narikazu, Hyodo, Ichinosuke, Muro, Kei
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - genetics; Adenocarcinoma - mortality; Adenocarcinoma - pathology; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers, Tumor - genetics; Cetuximab; Cetuximab - administration & dosage; Cetuximab - adverse effects; Chemotherapy; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; Drug Resistance, Neoplasm; Epidermal growth factor receptor; Female; Fluorouracil - administration & dosage; Fluorouracil - adverse effects; Humans; Irinotecan; Irinotecan - administration & dosage; Irinotecan - adverse effects; Male; Metastatic colorectal cancer; Middle Aged; Mutation; Oxaliplatin - administration & dosage; Oxaliplatin - adverse effects; Panitumumab; Panitumumab - administration & dosage; Panitumumab - adverse effects; Progression-Free Survival; Proto-Oncogene Proteins p21(ras) - genetics; Time Factors
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2020.04.014

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 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. 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