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Title: | Cetuximab Alone or With Irinotecan for Resistant KRAS-, NRAS-, BRAF- and PIK3CA-wild-type Metastatic Colorectal Cancer: The AGITG Randomized Phase II ICECREAM Study. | Authors: | Segelov E. ;Waring P.M.;Tejpar S.;Khasraw M.;Van Hazel G.A.;Simes J.;Gebski V.J.;Desai J.;Shapiro J.D.;Thavaneswaran S.;Underhill C.R.;Robledo K.P.;Karapetis C.S.;Day F.L.;Nott L.M.;Jefford M.;Chantrill L.A.;Pavlakis N.;Tebbutt N.C.;Price T.J. | Monash Health Department(s): | Oncology | Institution: | (Shapiro) Cabrini Haematology and Oncology Centre, Cabrini Hospital and Monash University, Malvern, Victoria, Australia (Thavaneswaran, Robledo, Khasraw, Simes, Gebski) National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Camperdown, New South Wales, Australia (Underhill) Albury-Wodonga Regional Cancer Centre and University of New South Wales, East Albury, New South Wales, Australia (Karapetis) Department of Medical Oncology, Flinders Medical Centre and Flinders Centre for Innovation in Cancer, Flinders University, Bedford Park, South Australia, Australia (Day) Department of Medical Oncology, Calvary Mater Newcastle Hospital and University of Newcastle, Waratah, New South Wales, Australia (Nott) Department of Medical Oncology, Royal Hobart Hospital, Hobart, Tasmania, Australia (Jefford) Department of Medical Oncology, Peter MacCallum Cancer Centre, Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia (Chantrill) Department of Medical Oncology, Kinghorn Cancer Centre, St Vincent's Hospital and University of New South Wales, Darlinghurst, New South Wales, Australia (Pavlakis) Northern Cancer Institute, Royal North Shore Hospital, University of Sydney, St Leonards, New South Wales, Australia (Tebbutt) Department of Medical Oncology, Austin Health, Heidelberg, Victoria, Australia (Price) Medical Oncology Unit, Queen Elizabeth Hospital and Lyell McEwin Hospital, Elizabeth Vale, South Australia, Australia (Khasraw) Department of Medical Oncology, Geelong Hospital, Geelong, Victoria, Australia (Van Hazel) School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia (Waring) Department of Pathology, University of Melbourne, Melbourne, Victoria, Australia (Tejpar) Oncology Department, University Hospital Leuven, Leuven, Belgium (Desai) Department of Medical Oncology, Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia (Segelov) Department of Oncology, Monash Health and Monash University, Clayton, Victoria, Australia | Issue Date: | 28-Nov-2018 | Copyright year: | 2018 | Publisher: | Elsevier Inc. (E-mail: usjcs@elsevier.com) | Place of publication: | United States | Publication information: | Clinical Colorectal Cancer. 17 (4) (pp 313-319), 2018. Date of Publication: December 2018. | Journal: | Clinical Colorectal Cancer | Abstract: | Most unresectable metastatic colon cancer remains incurable, with a median survival of less than 3 years. Molecularly targeted therapies have recently been developed; in particular, monoclonal antibodies against the epidermal growth factor receptor, which are efficacious in 40% to 60% of chemotherapy-resistant patients with wild-type KRAS. This study shows that cetuximab plus irinotecan, compared with cetuximab alone, increases the response rate and delays progression in irinotecan-resistant RAS wild-type colorectal cancer. Background(s): 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. Result(s): 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(s): 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.Copyright © 2018 | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1016/j.clcc.2018.06.002 | ORCID: | Jefford, Michael; ORCID: http://orcid.org/0000-0002-8792-7807 Price, Timothy. J.; ORCID: http://orcid.org/0000-0002-3922-2693 | Link to associated publication: | Click here for full text options | PubMed URL: | 30463680 [http://www.ncbi.nlm.nih.gov/pubmed/?term=30463680] | ISSN: | 1533-0028 | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/37234 | Type: | Article | Subjects: | multicenter study overall survival phase 2 clinical trial progression free survival quality of life randomized controlled trial rectum sigmoid skin disease/si [Side Effect] transverse colon article treatment duration unspecified side effect/si [Side Effect] B Raf kinase/ec [Endogenous Compound] adult *metastatic colorectal cancer/dt [Drug Therapy] monotherapy disease exacerbation drug efficacy drug safety drug tolerability female human loading drug dose male *metastatic colorectal cancer/dm [Disease Management] molecularly targeted therapy aged *cetuximab/ae [Adverse Drug Reaction] *cetuximab/cb [Drug Combination] *cetuximab/cm [Drug Comparison] *cetuximab/dt [Drug Therapy] *cetuximab/to [Drug Toxicity] *cetuximab/iv [Intravenous Drug Administration] epidermal growth factor receptor/ec [Endogenous Compound] *irinotecan/ae [Adverse Drug Reaction] *irinotecan/cb [Drug Combination] *irinotecan/cm [Drug Comparison] *irinotecan/dt [Drug Therapy] K ras protein/ec [Endogenous Compound] *phosphatidylinositol 3 kinase/ec [Endogenous Compound] Ras protein/ec [Endogenous Compound] unclassified drug n ras protein/ec [Endogenous Compound] *cancer combination chemotherapy *cancer resistance clinical article controlled study skin disease / side effect adult aged Article *cancer combination chemotherapy *cancer resistance clinical article controlled study disease exacerbation drug efficacy drug safety drug tolerability female human loading drug dose male *metastatic colorectal cancer / *disease management / *drug therapy molecularly targeted therapy monotherapy multicenter study overall survival phase 2 clinical trial progression free survival quality of life randomized controlled trial rectum sigmoid transverse colon treatment duration unspecified side effect / side effect |
Type of Clinical Study or Trial: | Randomised controlled trial |
Appears in Collections: | Articles |
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