P-0240 - A phase II study of panitumumab plus irinotecan for metastatic colorectal cancer patients with wild KRAS exon 2, resistant to fluoropyrimidine, oxal...

Date 28 June 2014
Event World GI 2014
Session Poster Session
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Presenter Taishi Hata
Citation Annals of Oncology (2014) 25 (suppl_2): ii14-ii104. 10.1093/annonc/mdu165
Authors T. Hata1, M. Fukunaga2, T. Kato3, Y. Miyake4, K. Takeda5, T. Yoshinami6, H. Daga5, M. Yoshida7, K. Taira8, Y. Tokunaga9, S. Kuwakado7, H. Hasegawa10
  • 1Osaka Univercity Graduate School of Medicine, Dept of Gastroenterological Surgery, Suita/JP
  • 2Sakai City Hospital, Dept of Surgery, Sakai/JP
  • 3Kansai Rosai Hospital, Dept of Surgery, Amagasaki/JP
  • 4Nishinomiya Municipal Central Hospital, Dept of Surgery, Nishinomiya/JP
  • 5Osaka City General Hospital, Dept of Medical Oncology, Osaka/JP
  • 6Osaka Medical Center for Cancer and Cardiovascular Disease, Medical Oncology, Osaka/JP
  • 7Osaka Medical College Hospital, Dept of Cancer Chemotherapy Center, Takatsuki/JP
  • 8Machida Gastroenterical Hospital, Dept of Medical Oncology, Osaka/JP
  • 9Kyoto Teishin Hospital, Dept of Surgery, Kyoto/JP
  • 10Department of Gastroenterology and Hepatology, Osaka National Hospital, Osaka/JP



Anti-Epidermal growth factor receptor (EGFR) antibody therapy showed to be effective in treatment for metastatic colorectal cancer (mCRC) with wild KRAS exon 2. Recently, KRAS exon 3, exon 4 and NRAS mutations were reported negative predictive for efficacy to anti-EGFR therapy as same as KRAS exon 2 mutation, according to biomarker analysis of several trials. In BOND 1 trial, combination chemotherapy with cetuximab plus irinotecan showed more effective than anti-EGFR antibody alone, resistant to irinotecan. However, combination chemotherapy with panitumumab plus irinotecan has never reported definitely more effective than panitumumab monotherapy in randomized trial. We conducted a phase II trial of panitumumab plus irinotecan for mCRC patients with wild KRAS resistant to fluoropyrimidine, oxaliplatin and irinotecan in Japanese.


Subjects were mCRC patients with wild KRAS exon 2, who showed resistance to fluoropyrimidine, oxaliplatin and irinotecan and had measurable disease, ECOG PS 0-2. Panitumumab (6 mg/kg) plus irinotecan (same dose as prior irinotecan) was administered every two weeks. This treatment was provided until progression. The primary endpoint was response rate (RR). Secondary endpoints were disease control rate (DCR), progression free survival (PFS), overall survival (OS), response duration, and adverse event (AE).


A total of 31 subjects were enrolled between July 2010 and July 2012. Median age was 64 years old (range 42-74). Male 20 / Female 11, colon 20 / rectum 11, ECOG PS 0 / 1 : 15 / 16, prior regimen 1 / 2 / 3 / ≧4 : 1 / 22 / 5 / 3. Nineteen patients had liver metastasis, 11 had lung metastasis, 3 had lymph node metastasis and 2 had peritoneal metastasis. An independent review committee evaluated for efficacy in eligible 31 subjects in accordance with the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The RR of primary endpoint was 29.0% (95% confidence interval (CI), 14.2-48.0%). DCR was 74.2% (95%CI, 55.4-88.1%), median PFS was 5.6 months (95%CI: 3.4-8.1) and median OS was 10.6 months (95%CI: 6.9-15.8). In 31 subjects for safety evaluation, the incidence of any Grade 3 or greater adverse events was 58.1%. Major adverse events of Grade 3 were diarrhea (19.4%), rash acneiform (12.9%), fatigue (9.7%), anorexia (9.7%). A sudden death and an infusion related reaction occurred.


Combination chemotherapy with panitumumab plus irinotecan was demonstrated to be safe and better RR, DCR, PFS and OS than Japanese single arm phase II of panitumumab alone for mCRC, resistant to fluoropyrimidine, oxaliplatin and irinotecan, respectively. This result in Japanese was equal to other reports of panitumumab plus irinotecan.