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. 2014 Sep;13(3):164-71.
doi: 10.1016/j.clcc.2014.06.001. Epub 2014 Jun 23.

Progression-free survival remains poor over sequential lines of systemic therapy in patients with BRAF-mutated colorectal cancer

Van Morris  1 , Michael J Overman  2 , Zhi-Qin Jiang  2 , Christopher Garrett  2 , Shweta Agarwal  2 , Cathy Eng  2 , Bryan Kee  2 , David Fogelman  2 , Arvind Dasari  2 , Robert Wolff  2 , Dipen Maru  3 , Scott Kopetz  4
Affiliations

Progression-free survival remains poor over sequential lines of systemic therapy in patients with BRAF-mutated colorectal cancer

Van Morris et al. Clin Colorectal Cancer. 2014 Sep.

Abstract

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.

Keywords: Biomarker; Chemotherapy; Mutation; Prognosis; Recurrence.

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Conflict of interest statement

Conflicts of Interest: Dr. Kopetz is supported by CA172670. The remaining authors report no conflicts of interest.

Figures

Figure 1
Figure 1
Overall Survival According to Stage at Diagnosis
Figure 2
Figure 2
Progression-Free Survival by Line of Therapy
See this image and copyright information in PMC

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