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Investigating the poor outcomes of BRAF-mutant advanced colorectal cancer: Analysis from 2530 patients in randomised clinical trials.

Seligmann, JF; Fisher, D; Smith, CG; Richman, SD; Elliott, F; Brown, S; Adams, R; ... Middleton, G; + view all (2017) Investigating the poor outcomes of BRAF-mutant advanced colorectal cancer: Analysis from 2530 patients in randomised clinical trials. Annals of Oncology , 28 (3) pp. 562-568. 10.1093/annonc/mdw645. Green open access

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Abstract

BACKGROUND: To improve strategies for the treatment of BRAF-mutant advanced colorectal cancer (aCRC) patients we examined individual data from patients treated with chemotherapy alone in three randomised trials to identify points on the treatment pathway where outcomes differ from BRAF wild-types. PATIENTS AND METHODS: 2530 aCRC patients were assessed from three randomised trials. End-points were progression free survival (PFS), response rate (RR), disease control rate (DCR), post-progression survival (P-PS) and overall survival (OS). Treatments included first-line oxaliplatin/fluorouracil (OxFU), and second-line irinotecan. Clinicians were unaware of BRAF-status RESULTS: 231 patients (9.1%) had BRAF-mutant tumours. BRAF-mutation conferred significantly worse survival independent of associated clinicopathological factors known to be prognostic. Compared with wild-type, BRAF-mutant patients treated with first-line OxFU had similar DCR (59.2% vs 72%; adjusted OR=0.76,p=0.24) and PFS (5.7 vs 6.3 months; adjusted HR=1.14, p=0.26). Following progression on first-line chemotherapy, BRAF-mutant patients had a markedly shorter P-PS (4.2 vs 9.2 months, adjusted HR=1.69,p<0.001).Fewer BRAF-mutant patients received second-line treatment (33% vs 51%, p<0.001), but BRAF-mutation was not associated with inferior second-line outcomes (RR adjusted OR=0.56, p=0.45; PFS adjusted HR=1.01, p=0.93).Significant clinical heterogeneity within the BRAF-mutant population was observed: a proportion (24.3%) had good first-line PFS and P-PS (both >6 months; OS=24.0 months), however 36.5% progressed rapidly through first-line chemotherapy and thereafter, with OS=4.7 months. CONCLUSIONS: BRAF-mutant aCRC confers a markedly worse prognosis independent of associated clinicopathological features. Chemotherapy provides meaningful improvements in outcome throughout treatment lines. Post-progression survival is markedly worse and vigilance is required to ensure appropriate delivery of treatment after first-line progression.

Type: Article
Title: Investigating the poor outcomes of BRAF-mutant advanced colorectal cancer: Analysis from 2530 patients in randomised clinical trials.
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/annonc/mdw645
Publisher version: https://doi.org/10.1093/annonc/mdw645
Language: English
Additional information: This is a pre-copyedited, author-produced PDF of an article accepted for publication in Annals Of Oncology following peer review. The version of record J.F. Seligmann, D. Fisher, C.G. Smith, S.D. Richman, F. Elliott, S. Brown, R. Adams, T. Maughan, P. Quirke, J. Cheadle, M. Seymour, G. Middleton; Investigating the poor outcomes of BRAF-mutant advanced colorectal cancer: analysis from 2530 patients in randomised clinical trials. Ann Oncol 2016 mdw645., is available online at: http://dx.doi.org/10.1093/annonc/mdw645.
Keywords: BRAF-mutant, Colorectal cancer, chemotherapy, prognosis
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
URI: https://discovery.ucl.ac.uk/id/eprint/1534900
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