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

Jeremy D Shapiro¹, Subotheni Thavaneswaran², Craig R Underhill³, Kristy P Robledo², Christos S Karapetis⁴, Fiona L Day⁵, Louise M Nott⁶, Michael Jefford⁷, Lorraine A Chantrill⁸, Nick Pavlakis⁹, Niall C Tebbutt¹⁰, Timothy J Price¹¹, Mustafa Khasraw¹², Guy A Van Hazel¹³, Paul M Waring¹⁴, Sabine Tejpar¹⁵, John Simes², Val J Gebski², Jayesh Desai¹⁶, Eva Segelov¹⁷

Affiliations

¹ Cabrini Haematology and Oncology Centre, Cabrini Hospital and Monash University, Malvern, Victoria, Australia. Electronic address: jeremy.shapiro@monash.edu.
² National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Camperdown, New South Wales, Australia.
³ Albury-Wodonga Regional Cancer Centre and University of New South Wales, East Albury, New South Wales, Australia.
⁴ Department of Medical Oncology, Flinders Medical Centre and Flinders Centre for Innovation in Cancer, Flinders University, Bedford Park, South Australia, Australia.
⁵ Department of Medical Oncology, Calvary Mater Newcastle Hospital and University of Newcastle, Waratah, New South Wales, Australia.
⁶ Department of Medical Oncology, Royal Hobart Hospital, Hobart, Tasmania, Australia.
⁷ Department of Medical Oncology, Peter MacCallum Cancer Centre, Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia.
⁸ Department of Medical Oncology, Kinghorn Cancer Centre, St Vincent's Hospital and University of New South Wales, Darlinghurst, New South Wales, Australia.
⁹ Northern Cancer Institute, Royal North Shore Hospital, and University of Sydney, St Leonards, New South Wales, Australia.
¹⁰ Department of Medical Oncology, Austin Health, Heidelberg, Victoria, Australia.
¹¹ Medical Oncology Unit, Queen Elizabeth Hospital and Lyell McEwin Hospital, Elizabeth Vale, South Australia, Australia.
¹² National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Camperdown, New South Wales, Australia; Department of Medical Oncology, Geelong Hospital, Geelong, Victoria, Australia.
¹³ School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia.
¹⁴ Department of Pathology, University of Melbourne, Melbourne, Victoria, Australia.
¹⁵ Oncology Department, University Hospital Leuven, Leuven, Belgium.
¹⁶ Department of Medical Oncology, Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
¹⁷ Department of Oncology, Monash Health and Monash University, Clayton, Victoria, Australia.

PMID: 30463680
DOI: 10.1016/j.clcc.2018.06.002

Clinical Trial

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

Jeremy D Shapiro et al. Clin Colorectal Cancer. 2018 Dec.

. 2018 Dec;17(4):313-319.

doi: 10.1016/j.clcc.2018.06.002. Epub 2018 Jun 8.

Authors

Affiliations

¹ Cabrini Haematology and Oncology Centre, Cabrini Hospital and Monash University, Malvern, Victoria, Australia. Electronic address: jeremy.shapiro@monash.edu.
² National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Camperdown, New South Wales, Australia.
³ Albury-Wodonga Regional Cancer Centre and University of New South Wales, East Albury, New South Wales, Australia.
⁴ Department of Medical Oncology, Flinders Medical Centre and Flinders Centre for Innovation in Cancer, Flinders University, Bedford Park, South Australia, Australia.
⁵ Department of Medical Oncology, Calvary Mater Newcastle Hospital and University of Newcastle, Waratah, New South Wales, Australia.
⁶ Department of Medical Oncology, Royal Hobart Hospital, Hobart, Tasmania, Australia.
⁷ Department of Medical Oncology, Peter MacCallum Cancer Centre, Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia.
⁸ Department of Medical Oncology, Kinghorn Cancer Centre, St Vincent's Hospital and University of New South Wales, Darlinghurst, New South Wales, Australia.
⁹ Northern Cancer Institute, Royal North Shore Hospital, and University of Sydney, St Leonards, New South Wales, Australia.
¹⁰ Department of Medical Oncology, Austin Health, Heidelberg, Victoria, Australia.
¹¹ Medical Oncology Unit, Queen Elizabeth Hospital and Lyell McEwin Hospital, Elizabeth Vale, South Australia, Australia.
¹² National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Camperdown, New South Wales, Australia; Department of Medical Oncology, Geelong Hospital, Geelong, Victoria, Australia.
¹³ School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia.
¹⁴ Department of Pathology, University of Melbourne, Melbourne, Victoria, Australia.
¹⁵ Oncology Department, University Hospital Leuven, Leuven, Belgium.
¹⁶ Department of Medical Oncology, Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
¹⁷ Department of Oncology, Monash Health and Monash University, Clayton, Victoria, Australia.

PMID: 30463680
DOI: 10.1016/j.clcc.2018.06.002

Abstract

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.

Keywords: Cetuximab; Chemotherapy colon cancer; Irinotecan; RAS.

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

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

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