Phase 2 Trial of Bi-weekly Cetuximab for Recurrent or Metastatic Colorectal Cancer (BIC-K Trial)
Authors: Naoko Chayahara, Naomi Kiyota, Masanori Toyoda, Toru Mukohara, Yoshimi Fujishima, Akihito Tsuji, Hironaga Satake, Sahchiko Kimura, Masahito Kotaka, Hironobu Minami
Journal: Annals of Oncology (2016)

Background: Cetuximab (Cmab) is effective against metastatic colorectal cancer (mCRC) of the RAS wild type. However, administration is weekly, and thus inconvenient for patients (pts). We conducted a Phase II trial to evaluate the efficacy and safety of bi-weekly Cmab (B-C) for pts with KRAS wild type mCRC.Methods: mCRC pts with KRAS wild type who showed resistance/intolerance to fluoropyrimidine, oxaliplatin and irinotecan were administered Cmab (500mg/m2) every 2 weeks. Following disease progression, Cmab (500mg/m2) and irinotecan (150mg/m2) (B-CI) were administered every 2 weeks for exploratory analysis, if feasible. We also checked somatic mutations (MT), including other KRAS, NRAS, BRAF and PIK3CA. Primary endpoint was disease control rate (DCR), and secondary endpoints were overall survival (OS), overall response rate (ORR), progression-free survival (PFS) and adverse events (AE). We set the null hypothesis of 15% of DCR and the alternative of 50% for sample size calculation with a two-sided alfa of 0.05 and power of 0.9. Thus, total sample size was estimated to be 20 pts.Results: From April 2012 to September 2014, 20 pts were enrolled. Patient characteristics were median age 65.5 years old (range 32-88), male/female 14/6, ECOG PS 0/1 in 8/12, colon/rectum in 9/11, and unresectable/recurrent in 10/10. DCR was 40.0% (95%CI: 18.5-61.5), ORR was 15.0% (95%CI: 0-30.6), median OS was 11.6 months, and median PFS was 3.2 months. Major AE were acne-like rash (Grade 3: 15%), paronychia (Grade 3: 10%), dry skin (Grade 3: 5%), hypomagnesemia and pruritus. Thirteen of 17 pts were administrated B-CI after progression. DCR of B-CI was 38.4% and median PFS was 3.4 months. On somatic mutational analysis, we found other KRAS MT in 1, BRAF MT in 2 and PIK3CA MT in 1. NRAS MT was not found.Conclusions: This study suggests that B-C is equivalent to weekly Cmab in efficacy and toxicity. Final results of mutational analysis and other biomarkers await further analysis. Background: Cetuximab (Cmab) is effective against metastatic colorectal cancer (mCRC) of the RAS wild type. However, administration is weekly, and thus inconvenient for patients (pts). We conducted a Phase II trial to evaluate the efficacy and safety of bi-weekly Cmab (B-C) for pts with KRAS wild type mCRC. Methods: mCRC pts with KRAS wild type who showed resistance/intolerance to fluoropyrimidine, oxaliplatin and irinotecan were administered Cmab (500mg/m2) every 2 weeks. Following disease progression, Cmab (500mg/m2) and irinotecan (150mg/m2) (B-CI) were administered every 2 weeks for exploratory analysis, if feasible. We also checked somatic mutations (MT), including other KRAS, NRAS, BRAF and PIK3CA. Primary endpoint was disease control rate (DCR), and secondary endpoints were overall survival (OS), overall response rate (ORR), progression-free survival (PFS) and adverse events (AE). We set the null hypothesis of 15% of DCR and the alternative of 50% for sample size calculation with a two-sided alfa of 0.05 and power of 0.9. Thus, total sample size was estimated to be 20 pts. Results: From April 2012 to September 2014, 20 pts were enrolled. Patient characteristics were median age 65.5 years old (range 32-88), male/female 14/6, ECOG PS 0/1 in 8/12, colon/rectum in 9/11, and unresectable/recurrent in 10/10. DCR was 40.0% (95%CI: 18.5-61.5), ORR was 15.0% (95%CI: 0-30.6), median OS was 11.6 months, and median PFS was 3.2 months. Major AE were acne-like rash (Grade 3: 15%), paronychia (Grade 3: 10%), dry skin (Grade 3: 5%), hypomagnesemia and pruritus. Thirteen of 17 pts were administrated B-CI after progression. DCR of B-CI was 38.4% and median PFS was 3.4 months. On somatic mutational analysis, we found other KRAS MT in 1, BRAF MT in 2 and PIK3CA MT in 1. NRAS MT was not found. Conclusions: This study suggests that B-C is equivalent to weekly Cmab in efficacy and toxicity. Final results of mutational analysis and other biomarkers await further analysis.