TY - JOUR
T1 - Progression-free survival remains poor over sequential lines of systemic therapy in patients with BRAF-mutated colorectal cancer
AU - Morris, Van
AU - Overman, Michael J.
AU - Jiang, Zhi Qin
AU - Garrett, Christopher
AU - Agarwal, Shweta
AU - Eng, Cathy
AU - Kee, Bryan
AU - Fogelman, David
AU - Dasari, Arvind
AU - Wolff, Robert
AU - Maru, Dipen
AU - Kopetz, Scott
N1 - Publisher Copyright:
© 2014 Elsevier Ltd. All rights reserved.
PY - 2014/9/1
Y1 - 2014/9/1
N2 - Background BRAF mutations occur in 5% to 10% of metastatic colorectal cancers and are biomarkers associated with a poor prognosis. However, the outcomes with standard chemotherapy over sequential lines of therapy in a large cohort of patients with BRAF-mutant tumors have not been described.Patients and Methods We searched the M.D. Anderson Cancer Center databases for patients with colorectal cancer and identified BRAF mutations between December 2003 and May 2012. Patients were analyzed for clinical characteristics, PFS, overall survival, and chemotherapeutic agents used. Survival was estimated according to the Kaplan-Meier method.Results Among the 1567 patients tested for BRAF mutations at our institution, 127 (8.1%) had tumors with BRAF mutations. The 71 patients who presented with metastatic disease received a median of 2 lines of chemotherapy. For the first 3 lines of chemotherapy, median PFS was 6.3 months (n = 69 patients; 95% confidence interval [CI], 4.9-7.7 months), 2.5 months (n = 58 patients; 95% CI, 1.8-3.0 months), and 2.6 months (n = 31 patients; 95% CI, 1.0-4.2 months), respectively. Median PFS was not affected by the backbone chemotherapeutic agent in the first-line setting, whether oxaliplatin-based or irinotecan-based (6.4 months vs. 5.4 months, respectively; P =.99).Conclusion PFS is expectedly poor for patients with BRAF-mutated metastatic colorectal cancer. Despite the ascertainment bias present (with testing preferentially performed in patients suitable for clinical trials in refractory disease), these data provide historic controls suitable for future study design and support the idea that novel therapeutic options are essential in this population.
AB - Background BRAF mutations occur in 5% to 10% of metastatic colorectal cancers and are biomarkers associated with a poor prognosis. However, the outcomes with standard chemotherapy over sequential lines of therapy in a large cohort of patients with BRAF-mutant tumors have not been described.Patients and Methods We searched the M.D. Anderson Cancer Center databases for patients with colorectal cancer and identified BRAF mutations between December 2003 and May 2012. Patients were analyzed for clinical characteristics, PFS, overall survival, and chemotherapeutic agents used. Survival was estimated according to the Kaplan-Meier method.Results Among the 1567 patients tested for BRAF mutations at our institution, 127 (8.1%) had tumors with BRAF mutations. The 71 patients who presented with metastatic disease received a median of 2 lines of chemotherapy. For the first 3 lines of chemotherapy, median PFS was 6.3 months (n = 69 patients; 95% confidence interval [CI], 4.9-7.7 months), 2.5 months (n = 58 patients; 95% CI, 1.8-3.0 months), and 2.6 months (n = 31 patients; 95% CI, 1.0-4.2 months), respectively. Median PFS was not affected by the backbone chemotherapeutic agent in the first-line setting, whether oxaliplatin-based or irinotecan-based (6.4 months vs. 5.4 months, respectively; P =.99).Conclusion PFS is expectedly poor for patients with BRAF-mutated metastatic colorectal cancer. Despite the ascertainment bias present (with testing preferentially performed in patients suitable for clinical trials in refractory disease), these data provide historic controls suitable for future study design and support the idea that novel therapeutic options are essential in this population.
KW - Biomarker
KW - Chemotherapy
KW - Mutation
KW - Prognosis
KW - Recurrence
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U2 - 10.1016/j.clcc.2014.06.001
DO - 10.1016/j.clcc.2014.06.001
M3 - Article
C2 - 25069797
AN - SCOPUS:84908219463
SN - 1533-0028
VL - 13
SP - 164
EP - 171
JO - Clinical colorectal cancer
JF - Clinical colorectal cancer
IS - 3
ER -