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Predictive and prognostic roles of BRAF mutation in stage III colon cancer : results from intergroup trial CALGB 89803 . PURPOSE Alterations in the RAS-RAF-MAP2K ( MEK ) -MAPK signaling pathway are major drivers in colorectal carcinogenesis . In colorectal cancer , BRAF mutation is associated with microsatellite instability ( MSI ) , and typically predicts inferior prognosis . We examined the effect of BRAF mutation on survival and treatment efficacy in patients with stage III colon cancer . METHODS We assessed status of BRAF c.1799T > A ( p.V600E ) mutation and MSI in 506 stage III colon cancer patients enrolled in a randomized adjuvant chemotherapy trial [ 5-fluorouracil and leucovorin ( FU/LV ) vs. irinotecan ( CPT11 ) , FU and LV ( IFL ) ; CALGB 89803 ] . Cox proportional hazards model was used to assess the prognostic role of BRAF mutation , adjusting for clinical features , adjuvant chemotherapy arm , and MSI status . RESULTS Compared with 431 BRAF wild-type patients , 75 BRAF-mutated patients experienced significantly worse overall survival [ OS ; log-rank P = 0.015 ; multivariate HR = 1.66 ; 95 % CI : 1.05-2.63 ] . By assessing combined status of BRAF and MSI , it seemed that BRAF-mutated MSS ( microsatellite stable ) tumor was an unfavorable subtype , whereas BRAF wild-type MSI-high tumor was a favorable subtype , and BRAF-mutated MSI-high tumor and BRAF wild-type MSS tumor were intermediate subtypes . Among patients with BRAF-mutated tumors , a nonsignificant trend toward improved OS was observed for IFL versus FU/LV arm ( multivariate HR = 0.52 ; 95 % CI : 0.25-1.10 ) . Among patients with BRAF wild-type cancer , IFL conferred no suggestion of benefit beyond FU/LV alone ( multivariate HR = 1.02 ; 95 % CI : 0.72-1.46 ) . CONCLUSIONS BRAF mutation is associated with inferior survival in stage III colon cancer . Additional studies are necessary to assess whether there is any predictive role of BRAF mutation for irinotecan-based therapy .
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Intervention_Other
status of BRAF c.1799T > A ( p.V600E ) mutation and MSI
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Intervention_Pharmacological
irinotecan ( CPT11 ) , FU and LV ( IFL ) ;
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Intervention_Pharmacological
chemotherapy
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Intervention_Pharmacological
IFL
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Intervention_Pharmacological
FU/LV
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Intervention_Pharmacological
IFL
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Intervention_Pharmacological
FU/LV
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Intervention_Pharmacological
irinotecan-based therapy
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Outcome_Mortality
overall survival [ OS
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Outcome_Mortality
OS
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Outcome_Mortality
survival
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Participant_Condition
stage III colon cancer
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Participant_Condition
colorectal carcinogenesis
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Participant_Condition
patients with stage III colon cancer
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Participant_Sample-size
506
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Participant_Condition
stage III colon cancer
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Participant_Sample-size
75
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Participant_Condition
stage III colon cancer