TY - JOUR
T1 - Investigating the poor outcomes of BRAF-mutant advanced colorectal cancer
T2 - Analysis from 2530 patients in randomised clinical trials
AU - Seligmann, J F
AU - Fisher, D
AU - Smith, C G
AU - Richman, S D
AU - Elliott, F
AU - Brown, S
AU - Adams, R
AU - Maughan, T
AU - Quirke, P
AU - Cheadle, J
AU - Seymour, M
AU - Middleton, G
N1 - © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
PY - 2017/3
Y1 - 2017/3
N2 - 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.
AB - 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.
KW - colorectal cancer
KW - BRAF-mutant
KW - chemotherapy
KW - prognosis
U2 - 10.1093/annonc/mdw645
DO - 10.1093/annonc/mdw645
M3 - Article
C2 - 27993800
SN - 0923-7534
VL - 28
SP - 562
EP - 568
JO - Annals of Oncology
JF - Annals of Oncology
IS - 3
ER -