1. Date of download: 6/22/2016 From: Systematic Review: Anti–Epidermal Growth Factor Receptor Treatment Effect Modification by KRAS Mutations in Advanced Colorectal Cancer Ann Intern Med. 2011;154(1):37-49. doi:10.7326/0003-4819-154-1-201101040-00006 Summary of evidence search and selection.RCT = randomized, controlled trial. Figure Legend: Copyright © American College of Physicians. All rights reserved.American College of Physicians

2. Date of download: 6/22/2016 From: Systematic Review: Anti–Epidermal Growth Factor Receptor Treatment Effect Modification by KRAS Mutations in Advanced Colorectal Cancer Ann Intern Med. 2011;154(1):37-49. doi:10.7326/0003-4819-154-1-201101040-00006 Overlap patterns in eligible studies.Each publication is represented by an ellipse, and ellipses of publications with at least partial overlap are linked. The graph indicates that a substantial amount of overlap is present: Of a total of 45 studies, only 24 reported on independent patient populations. Figure Legend: Copyright © American College of Physicians. All rights reserved.American College of Physicians

3. Date of download: 6/22/2016 From: Systematic Review: Anti–Epidermal Growth Factor Receptor Treatment Effect Modification by KRAS Mutations in Advanced Colorectal Cancer Ann Intern Med. 2011;154(1):37-49. doi:10.7326/0003-4819-154-1-201101040-00006 Survival and treatment failure analyses from randomized, controlled trials comparing anti-EGFR antibodies with cytotoxic chemotherapy or best supportive care.Forest plots on the left present results for the treatment effect (anti-EGFR antibody group vs. comparator), stratified by KRAS mutation status, for each clinical trial. These estimates are indicative of the treatment effect (anti-EGFR treatment group vs. control) within the subgroups of patients defined by KRAS mutation status. Circles represent the point estimate of the treatment effect among KRAS wild-type patients, and squares represent the point estimate of the treatment effect among KRAS-mutated patients. Forest plots on the right summarize the relative treatment effect within each of the 4 studies (KRAS mutant vs. wild-type). These estimates are comparing the treatment effects (anti-EGFR treatment group vs. control) between the groups defined by KRAS mutation status. For each estimate, horizontal lines indicate the 95% CI. Diamonds indicate the summary relative estimates (hazard ratios or odds ratios, as appropriate) by random-effects calculations; the width of the diamond represents the 95% CI of the summary estimates. EGFR = epidermal growth factor receptor. Top. Results for overall survival. Middle. Results for progression-free survival. Bottom. Results for treatment failure. Figure Legend: Copyright © American College of Physicians. All rights reserved.American College of Physicians

4. Date of download: 6/22/2016 From: Systematic Review: Anti–Epidermal Growth Factor Receptor Treatment Effect Modification by KRAS Mutations in Advanced Colorectal Cancer Ann Intern Med. 2011;154(1):37-49. doi:10.7326/0003-4819-154-1-201101040-00006 Survival and treatment failure analyses from randomized, controlled trials comparing anti-EGFR antibodies in combination with chemotherapy and bevacizumab versus chemotherapy and bevacizumab alone.Forest plots on the left present results for the treatment effect (anti-EGFR antibody group vs. comparator), stratified by KRAS mutation status, for each clinical trial. Circles represent the point estimate of the treatment effect among KRAS wild-type patients, and squares represent the point estimate of the treatment effect among KRAS-mutated patients. Forest plots on the right summarize the relative treatment effect within each of the 4 studies (KRAS mutant vs. wild-type). Reference 46 is represented by 2 strata because survival information was presented separately on the basis of cytotoxic chemotherapy regimens used. For each estimate, horizontal lines indicate the 95% CI. Diamonds indicate the summary relative estimates (hazard ratios or odds ratios, as appropriate) by random-effects calculations; the width of the diamond represents the 95% CI of the summary estimates. EGFR = epidermal growth factor receptor. Top. Results for overall survival. Middle. Results for progression-free survival. Bottom. Results for treatment failure. Figure Legend: Copyright © American College of Physicians. All rights reserved.American College of Physicians

5. Date of download: 6/22/2016 From: Systematic Review: Anti–Epidermal Growth Factor Receptor Treatment Effect Modification by KRAS Mutations in Advanced Colorectal Cancer Ann Intern Med. 2011;154(1):37-49. doi:10.7326/0003-4819-154-1-201101040-00006 Forest plot of HRs for overall survival comparingKRAS-mutated and wild-type patients.Each study is shown by the point estimate of the HR (size of square is proportional to the weight of each study) and 95% CI; the summary HR and its 95% CI by random-effects calculations are depicted by the diamond. Values greater than 1 indicate that patients with the KRAS mutation have reduced survival compared with wild-type patients. HR = hazard ratio. Figure Legend: Copyright © American College of Physicians. All rights reserved.American College of Physicians

6. Date of download: 6/22/2016 From: Systematic Review: Anti–Epidermal Growth Factor Receptor Treatment Effect Modification by KRAS Mutations in Advanced Colorectal Cancer Ann Intern Med. 2011;154(1):37-49. doi:10.7326/0003-4819-154-1-201101040-00006 Bivariate meta-analysis of sensitivity and specificity of KRAS mutations for predicting lack of response to anti-EGFR–based treatment.Study results are plotted in the receiver-operating characteristic curve space. Each study is represented by a circle, whose size is proportional to the study size. EGFR = epidermal growth factor receptor. Figure Legend: Copyright © American College of Physicians. All rights reserved.American College of Physicians