TY - JOUR
T1 - Characteristics of BRAFV600E Mutant, Deficient Mismatch Repair/Proficient Mismatch Repair, Metastatic Colorectal Cancer
T2 - A Multicenter Series of 287 Patients
AU - de la Fouchardière, Christelle
AU - Cohen, Romain
AU - Malka, David
AU - Guimbaud, Rosine
AU - Bourien, Héloïse
AU - Lièvre, Astrid
AU - Cacheux, Wulfran
AU - Artru, Pascal
AU - François, Eric
AU - Gilabert, Marine
AU - Samalin-Scalzi, Emmanuelle
AU - Zaanan, Aziz
AU - Hautefeuille, Vincent
AU - Rousseau, Benoit
AU - Senellart, Hélène
AU - Coriat, Romain
AU - Flippot, Ronan
AU - Desseigne, Françoise
AU - Lardy-Cleaud, Audrey
AU - Tougeron, David
N1 - Publisher Copyright:
© AlphaMed Press 2019
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Background: BRAFV600E mutations occurring in about 10% of metastatic colorectal cancers (mCRCs) are usually associated with a poor outcome. However, their prognostic factors are unknown. Materials and Methods: We built a multicenter clinico-biological database gathering data from patients with BRAFV600E-mutant mCRC treated in one of the 16 French centers from 2006 to 2017. The primary endpoint was to identify prognostic factors using a Cox model. Results: We included 287 patients (median age, 67 years [28–95]; female, 57%). Their median overall survival was 20.8 months (95% confidence interval [CI], 17.97–27.04), and median progression-free survival in the first-line setting was 4.34 months (95% CI, 3.81–5.03). Chemotherapy regimen and biological agents (antiangiogenic or anti-epidermal growth factor receptor) were not associated with overall and progression-free survival. Stage IV disease (synchronous metastases) and absence of curative-intent surgery were statistically associated with poor overall survival. Among the 194 patients with mismatch repair (MMR) status available, overall survival was significantly longer in patients with deficient MMR tumors compared with those with proficient MMR tumors (adjusted hazard ratio = 0.56; p =.009). Conclusion: Despite that BRAFV600E-mutant mCRCs are associated with poor overall and progression-free-survival, patients with deficient MMR tumors and/or resectable disease experienced a longer survival. These results highlight the importance of MMR testing and resectability discussion in patients with BRAFV600E mCRC in day-to-day practice. Implications for Practice: Mismatch repair (MMR) testing and resectability discussion in patients with BRAFV600E metastatic colorectal cancer (mCRC) should be performed in day-to-day practice to steer treatment decision making in patients with BRAFV600E-mutant mCRC.
AB - Background: BRAFV600E mutations occurring in about 10% of metastatic colorectal cancers (mCRCs) are usually associated with a poor outcome. However, their prognostic factors are unknown. Materials and Methods: We built a multicenter clinico-biological database gathering data from patients with BRAFV600E-mutant mCRC treated in one of the 16 French centers from 2006 to 2017. The primary endpoint was to identify prognostic factors using a Cox model. Results: We included 287 patients (median age, 67 years [28–95]; female, 57%). Their median overall survival was 20.8 months (95% confidence interval [CI], 17.97–27.04), and median progression-free survival in the first-line setting was 4.34 months (95% CI, 3.81–5.03). Chemotherapy regimen and biological agents (antiangiogenic or anti-epidermal growth factor receptor) were not associated with overall and progression-free survival. Stage IV disease (synchronous metastases) and absence of curative-intent surgery were statistically associated with poor overall survival. Among the 194 patients with mismatch repair (MMR) status available, overall survival was significantly longer in patients with deficient MMR tumors compared with those with proficient MMR tumors (adjusted hazard ratio = 0.56; p =.009). Conclusion: Despite that BRAFV600E-mutant mCRCs are associated with poor overall and progression-free-survival, patients with deficient MMR tumors and/or resectable disease experienced a longer survival. These results highlight the importance of MMR testing and resectability discussion in patients with BRAFV600E mCRC in day-to-day practice. Implications for Practice: Mismatch repair (MMR) testing and resectability discussion in patients with BRAFV600E metastatic colorectal cancer (mCRC) should be performed in day-to-day practice to steer treatment decision making in patients with BRAFV600E-mutant mCRC.
KW - BRAF
KW - Colorectal cancer
KW - Decision making
KW - Mismatch repair testing
KW - Prognostic
UR - http://www.scopus.com/inward/record.url?scp=85066833953&partnerID=8YFLogxK
U2 - 10.1634/theoncologist.2018-0914
DO - 10.1634/theoncologist.2018-0914
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C2 - 31152084
AN - SCOPUS:85066833953
SN - 1083-7159
VL - 24
SP - e1331-e1340
JO - Oncologist
JF - Oncologist
IS - 12
ER -