title: TP53 mutational status and cetuximab benefit in rectal cancer: 5-year results of the EXPERT-C trial.
abstract: In this updated analysis of the EXPERT-C trial we show that, in magnetic resonance imaging-defined, high-risk, locally advanced rectal cancer, adding cetuximab to a treatment strategy with neoadjuvant CAPOX followed by chemoradiotherapy, surgery, and adjuvant CAPOX is not associated with a statistically significant improvement in progression-free survival (PFS) and overall survival (OS) in both KRAS/BRAF wild-type and unselected patients. In a retrospective biomarker analysis, TP53 was not prognostic but emerged as an independent predictive biomarker for cetuximab benefit. After a median follow-up of 65.0 months, TP53 wild-type patients (n = 69) who received cetuximab had a statistically significant better PFS (89.3% vs 65.0% at 5 years; hazard ratio [HR] = 0.23; 95% confidence interval [CI] = 0.07 to 0.78; two-sided P = .02 by Cox regression) and OS (92.7% vs 67.5% at 5 years; HR = 0.16; 95% CI = 0.04 to 0.70; two-sided P = .02 by Cox regression) than TP53 wild-type patients who were treated in the control arm. An interaction between TP53 status and cetuximab effect was found (P < .05) and remained statistically significant after adjusting for statistically significant prognostic factors and KRAS.
authors: Affiliations of authors: Department of Medicine, The Royal Marsden NHS Foundation Trust, London and Surrey, UK (FS, DG, DC, SHW, SP, AD, AW, GB, DT, JO, IC); Medical Oncology Department, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain (JT); Department of Radiology, Oncology and Radiation Science, Akademiska Sjukhuset Uppsala, Uppsala, Sweden (BG); Department of Hematology and Medical Oncology, INCLIVA Biomedical Research Institute, University of Valencia, Hospital Clinico de Valencia, Valencia, Spain (AC).
authors: Francesco
authors: F
authors: Sclafani
authors: Affiliations of authors: Department of Medicine, The Royal Marsden NHS Foundation Trust, London and Surrey, UK (FS, DG, DC, SHW, SP, AD, AW, GB, DT, JO, IC); Medical Oncology Department, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain (JT); Department of Radiology, Oncology and Radiation Science, Akademiska Sjukhuset Uppsala, Uppsala, Sweden (BG); Department of Hematology and Medical Oncology, INCLIVA Biomedical Research Institute, University of Valencia, Hospital Clinico de Valencia, Valencia, Spain (AC).
authors: David
authors: D
authors: Gonzalez
authors: Affiliations of authors: Department of Medicine, The Royal Marsden NHS Foundation Trust, London and Surrey, UK (FS, DG, DC, SHW, SP, AD, AW, GB, DT, JO, IC); Medical Oncology Department, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain (JT); Department of Radiology, Oncology and Radiation Science, Akademiska Sjukhuset Uppsala, Uppsala, Sweden (BG); Department of Hematology and Medical Oncology, INCLIVA Biomedical Research Institute, University of Valencia, Hospital Clinico de Valencia, Valencia, Spain (AC). david.cunningham@rmh.nhs.uk.
authors: David
authors: D
authors: Cunningham
authors: Affiliations of authors: Department of Medicine, The Royal Marsden NHS Foundation Trust, London and Surrey, UK (FS, DG, DC, SHW, SP, AD, AW, GB, DT, JO, IC); Medical Oncology Department, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain (JT); Department of Radiology, Oncology and Radiation Science, Akademiska Sjukhuset Uppsala, Uppsala, Sweden (BG); Department of Hematology and Medical Oncology, INCLIVA Biomedical Research Institute, University of Valencia, Hospital Clinico de Valencia, Valencia, Spain (AC).
authors: Sanna
authors: S
authors: Hulkki Wilson
authors: Affiliations of authors: Department of Medicine, The Royal Marsden NHS Foundation Trust, London and Surrey, UK (FS, DG, DC, SHW, SP, AD, AW, GB, DT, JO, IC); Medical Oncology Department, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain (JT); Department of Radiology, Oncology and Radiation Science, Akademiska Sjukhuset Uppsala, Uppsala, Sweden (BG); Department of Hematology and Medical Oncology, INCLIVA Biomedical Research Institute, University of Valencia, Hospital Clinico de Valencia, Valencia, Spain (AC).
authors: Clare
authors: C
authors: Peckitt
authors: Affiliations of authors: Department of Medicine, The Royal Marsden NHS Foundation Trust, London and Surrey, UK (FS, DG, DC, SHW, SP, AD, AW, GB, DT, JO, IC); Medical Oncology Department, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain (JT); Department of Radiology, Oncology and Radiation Science, Akademiska Sjukhuset Uppsala, Uppsala, Sweden (BG); Department of Hematology and Medical Oncology, INCLIVA Biomedical Research Institute, University of Valencia, Hospital Clinico de Valencia, Valencia, Spain (AC).
authors: Josep
authors: J
authors: Tabernero
authors: Affiliations of authors: Department of Medicine, The Royal Marsden NHS Foundation Trust, London and Surrey, UK (FS, DG, DC, SHW, SP, AD, AW, GB, DT, JO, IC); Medical Oncology Department, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain (JT); Department of Radiology, Oncology and Radiation Science, Akademiska Sjukhuset Uppsala, Uppsala, Sweden (BG); Department of Hematology and Medical Oncology, INCLIVA Biomedical Research Institute, University of Valencia, Hospital Clinico de Valencia, Valencia, Spain (AC).
authors: Bengt
authors: B
authors: Glimelius
authors: Affiliations of authors: Department of Medicine, The Royal Marsden NHS Foundation Trust, London and Surrey, UK (FS, DG, DC, SHW, SP, AD, AW, GB, DT, JO, IC); Medical Oncology Department, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain (JT); Department of Radiology, Oncology and Radiation Science, Akademiska Sjukhuset Uppsala, Uppsala, Sweden (BG); Department of Hematology and Medical Oncology, INCLIVA Biomedical Research Institute, University of Valencia, Hospital Clinico de Valencia, Valencia, Spain (AC).
authors: Andrés
authors: A
authors: Cervantes
authors: Affiliations of authors: Department of Medicine, The Royal Marsden NHS Foundation Trust, London and Surrey, UK (FS, DG, DC, SHW, SP, AD, AW, GB, DT, JO, IC); Medical Oncology Department, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain (JT); Department of Radiology, Oncology and Radiation Science, Akademiska Sjukhuset Uppsala, Uppsala, Sweden (BG); Department of Hematology and Medical Oncology, INCLIVA Biomedical Research Institute, University of Valencia, Hospital Clinico de Valencia, Valencia, Spain (AC).
authors: Alice
authors: A
authors: Dewdney
authors: Affiliations of authors: Department of Medicine, The Royal Marsden NHS Foundation Trust, London and Surrey, UK (FS, DG, DC, SHW, SP, AD, AW, GB, DT, JO, IC); Medical Oncology Department, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain (JT); Department of Radiology, Oncology and Radiation Science, Akademiska Sjukhuset Uppsala, Uppsala, Sweden (BG); Department of Hematology and Medical Oncology, INCLIVA Biomedical Research Institute, University of Valencia, Hospital Clinico de Valencia, Valencia, Spain (AC).
authors: Andrew
authors: A
authors: Wotherspoon
authors: Affiliations of authors: Department of Medicine, The Royal Marsden NHS Foundation Trust, London and Surrey, UK (FS, DG, DC, SHW, SP, AD, AW, GB, DT, JO, IC); Medical Oncology Department, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain (JT); Department of Radiology, Oncology and Radiation Science, Akademiska Sjukhuset Uppsala, Uppsala, Sweden (BG); Department of Hematology and Medical Oncology, INCLIVA Biomedical Research Institute, University of Valencia, Hospital Clinico de Valencia, Valencia, Spain (AC).
authors: Gina
authors: G
authors: Brown
authors: Affiliations of authors: Department of Medicine, The Royal Marsden NHS Foundation Trust, London and Surrey, UK (FS, DG, DC, SHW, SP, AD, AW, GB, DT, JO, IC); Medical Oncology Department, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain (JT); Department of Radiology, Oncology and Radiation Science, Akademiska Sjukhuset Uppsala, Uppsala, Sweden (BG); Department of Hematology and Medical Oncology, INCLIVA Biomedical Research Institute, University of Valencia, Hospital Clinico de Valencia, Valencia, Spain (AC).
authors: Diana
authors: D
authors: Tait
authors: Affiliations of authors: Department of Medicine, The Royal Marsden NHS Foundation Trust, London and Surrey, UK (FS, DG, DC, SHW, SP, AD, AW, GB, DT, JO, IC); Medical Oncology Department, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain (JT); Department of Radiology, Oncology and Radiation Science, Akademiska Sjukhuset Uppsala, Uppsala, Sweden (BG); Department of Hematology and Medical Oncology, INCLIVA Biomedical Research Institute, University of Valencia, Hospital Clinico de Valencia, Valencia, Spain (AC).
authors: Jacqueline
authors: J
authors: Oates
authors: Affiliations of authors: Department of Medicine, The Royal Marsden NHS Foundation Trust, London and Surrey, UK (FS, DG, DC, SHW, SP, AD, AW, GB, DT, JO, IC); Medical Oncology Department, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain (JT); Department of Radiology, Oncology and Radiation Science, Akademiska Sjukhuset Uppsala, Uppsala, Sweden (BG); Department of Hematology and Medical Oncology, INCLIVA Biomedical Research Institute, University of Valencia, Hospital Clinico de Valencia, Valencia, Spain (AC).
authors: Ian
authors: I
authors: Chau
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068818:Cetuximab; D017024:Chemotherapy, Adjuvant; D017322:Clinical Trials, Phase II as Topic; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020360:Neoadjuvant Therapy / Q000379:methods*; D016017:Odds Ratio; D018714:Radiotherapy, Adjuvant; D016032:Randomized Controlled Trials as Topic; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D012189:Retrospective Studies; D012307:Risk Factors; D018401:Sample Size; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D000068818:Cetuximab