Inhibition of EGFR, HER2, and HER3 signalling in patients with colorectal cancer wild- type for BRAF, PIK3CA, KRAS, and NRAS (FOCUS4-D): a phase 2–3 randomised.

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Inhibition of EGFR, HER2, and HER3 signalling in patients with colorectal cancer wild- type for BRAF, PIK3CA, KRAS, and NRAS (FOCUS4-D): a phase 2–3 randomised trial  Prof Richard Adams, MD, Ewan Brown, MD, Louise Brown, PhD, Rachel Butler, PhD, Stephen Falk, FRCR, David Fisher, MSc, Prof Richard Kaplan, PhD, Prof Phil Quirke, PhD, Susan Richman, PhD, Leslie Samuel, FRCR, Jenny Seligmann, PhD, Prof Matt Seymour, PhD, Kai Keen Shiu, PhD, Harpreet Wasan, PhD, Prof Richard Wilson, PhD, Prof Tim Maughan, PhD  The Lancet Gastroenterology & Hepatology  Volume 3, Issue 3, Pages 162-171 (March 2018) DOI: 10.1016/S2468-1253(17)30394-1 Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Terms and Conditions

Figure 1 FOCUS4 trial programme schema Registration and randomisation processes and molecular stratification of patients in FOCUS4. Molecular cohorts are arranged in a hierarchy from left to right, such that a patient with both a PIK3CA and KRAS mutation will be classified in the PIK3CA mutation cohort. Red coloured letters indicate the FOCUS4 subtrials, with FOCUS4-D shaded grey. FFPE=formalin-fixed paraffin-embedded. The Lancet Gastroenterology & Hepatology 2018 3, 162-171DOI: (10.1016/S2468-1253(17)30394-1) Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Terms and Conditions

Figure 2 FOCUS4-D trial schema RECIST=Response Evaluation Criteria in Solid Tumors. *Criteria were age older than 17 years, no brain metastases, adequate organ function, WHO performance status 0–2, not pregnant, and CT scan within 4 weeks before randomisation. The Lancet Gastroenterology & Hepatology 2018 3, 162-171DOI: (10.1016/S2468-1253(17)30394-1) Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Terms and Conditions

Figure 3 Trial profile *Reasons for non-randomisation not recorded. The Lancet Gastroenterology & Hepatology 2018 3, 162-171DOI: (10.1016/S2468-1253(17)30394-1) Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Terms and Conditions

Figure 4 Progression-free survival (intention-to-treat analysis) HR=hazard ratio. The Lancet Gastroenterology & Hepatology 2018 3, 162-171DOI: (10.1016/S2468-1253(17)30394-1) Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Terms and Conditions