Cetuximab Alone or With Irinotecan for Resistant KRAS-, NRAS-, BRAF- and PIK3CA- wild-type Metastatic Colorectal Cancer: The AGITG Randomized Phase II ICECREAM Study Academic Article uri icon


  • BACKGROUND:The Irinotecan Cetuximab Evaluation and Cetuximab Response Evaluation (ICECREAM) study assessed the efficacy of cetuximab monotherapy compared with cetuximab combined with chemotherapy for quadruple wild-type (KRAS, NRAS, BRAF, or P13KCA exon 20) metastatic colorectal cancer. PATIENTS AND METHODS:Patients were enrolled in an open-label, multicenter, phase II trial and randomly assigned to cetuximab 400 mg/m2, then 250 mg/m2 cetuximab weekly, with or without irinotecan 180 mg/m2 every 2 weeks. The primary endpoint was 6-month progression-free survival; secondary endpoints were response rate, overall survival, toxicity, and quality of life. RESULTS:From 2012 to 2016, 48 patients were recruited. Two were ineligible, and 2 were not evaluable for response. Characteristics were balanced, except gender (male, 62% vs. 72%) and primary sidedness (left, 95% vs. 68%). For cetuximab compared with cetuximab-irinotecan, progression-free survival was 14% versus 41% (hazard ratio, 0.39; 95% confidence interval, 0.20-0.78; P = .008); response rate was 10% (2 partial responses) versus 38% (1 complete, 8 partial); P = .04. Grade 3 to 4 toxicities were less with cetuximab monotherapy (23% vs. 50%); global and specific quality of life scores did not differ. CONCLUSION:In comparison with cetuximab alone, cetuximab plus irinotecan increases the response rate and delays progression in irinotecan-resistant RAS wild-type colorectal cancer. This echoes data from molecularly unselected patients.


  • Shapiro, Jeremy D
  • Thavaneswaran, Subotheni
  • Underhill, Craig R
  • Robledo, Kristy P
  • Karapetis, Christos S
  • Day, Fiona L
  • Nott, Louise M
  • Jefford, Michael
  • Chantrill, Lorraine A
  • Pavlakis, Nick
  • Tebbutt, Niall C
  • Price, Timothy J
  • Khasraw, Mustafa
  • Van Hazel, Guy A
  • Waring, Paul M
  • Tejpar, Sabine
  • Simes, John
  • Gebski, Val J
  • Desai, Jayesh
  • Segelov, Eva

publication date

  • 2018

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