Treatment and Survival Outcome of BRAF-Mutated Metastatic Colorectal Cancer A Retrospective Matched Case-Control Study

Hamzeh Kayhanian; Emily Goode; Francesco Sclafani; Joo Ern Ang; Marco Gerlinger; David Gonzalez de Castro; Scott Shepherd; Clare Peckitt; Sheela Rao; David Watkins; Ian Chau; David Cunningham; Naureen Starling

doi:10.1016/j.clcc.2017.10.006

Treatment and Survival Outcome of BRAF-Mutated Metastatic Colorectal Cancer A Retrospective Matched Case-Control Study

Hamzeh Kayhanian, Emily Goode, Francesco Sclafani, Joo Ern Ang, Marco Gerlinger, David Gonzalez de Castro, Scott Shepherd, Clare Peckitt, Sheela Rao, David Watkins, Ian Chau, David Cunningham, Naureen Starling

School of Medicine, Dentistry and Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

50 Citations (Scopus)

Abstract

BACKGROUND

Somatic v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutation, present in approximately 10% of metastatic colorectal cancer (mCRC) cases, is associated with poor prognosis. Patient outcome outside of clinical trials has only been reported in small series. We report real-world data on treatment and survival for BRAF-mutated (MT) patients at a single tertiary center, compared with a matched BRAF wild type (WT) control group.

PATIENTS AND METHODS

All colorectal cancer patients tested for BRAF mutation, from October 2010 to November 2014 were identified. BRAF-MT mCRC cases were compared with an age and sex-matched BRAF-WT control group. Clinicopathological data were collected and survival calculated using the Kaplan-Meier method and comparisons made using Cox regression.

RESULTS

Forty-three of 503 patients (8.5%) tested had BRAF-MT mCRC and were compared with 88 BRAF-WT controls. Median overall survival (mOS) was 18.2 months for BRAF-MT and 41.1 months for BRAF-WT mCRC patients (hazard ratio, 2.74; 95% confidence interval, 1.60-4.70; P < .001). Progression-free survival for BRAF-MT and WT patients, respectively, was: 8.1 months versus 9.2 months (P = .571) first-line, 5.5 months versus 8.3 months (P = .074) second-line, and 1.8 months versus 5.6 months (P = .074) third-line. Treatment using sequential fluoropyrimidine-based doublet chemotherapy was similar between both groups. Anti-epidermal growth factor receptor (EGFR) therapy was mainly given third-line with progressive disease in 90% (n = 9 of 10) of BRAF-MT patients at first restaging.

CONCLUSION

In this case-control study, the poor mOS of BRAF-MT mCRC was associated with reduced treatment benefit beyond first-line. Sequential doublet chemotherapy remains a reasonable option in appropriately selected patients. BRAF-MT patients did not benefit from anti-EGFR therapy in this study. Recruitment to clinical trials is recommended to improve outcomes in BRAF-MT mCRC.

Original language	English
Journal	Clinical colorectal cancer
Volume	17
Issue number	1
Early online date	16 Oct 2017
DOIs	https://doi.org/10.1016/j.clcc.2017.10.006
Publication status	Published - Mar 2018

Keywords

Journal Article

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Kayhanian, H., Goode, E., Sclafani, F., Ang, J. E., Gerlinger, M., Gonzalez de Castro, D., Shepherd, S., Peckitt, C., Rao, S., Watkins, D., Chau, I., Cunningham, D., & Starling, N. (2018). Treatment and Survival Outcome of BRAF-Mutated Metastatic Colorectal Cancer A Retrospective Matched Case-Control Study. Clinical colorectal cancer, 17(1). https://doi.org/10.1016/j.clcc.2017.10.006

@article{c5db1426822b459c9c312f2282a61243,

title = "Treatment and Survival Outcome of BRAF-Mutated Metastatic Colorectal Cancer A Retrospective Matched Case-Control Study",

abstract = "BACKGROUNDSomatic v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutation, present in approximately 10% of metastatic colorectal cancer (mCRC) cases, is associated with poor prognosis. Patient outcome outside of clinical trials has only been reported in small series. We report real-world data on treatment and survival for BRAF-mutated (MT) patients at a single tertiary center, compared with a matched BRAF wild type (WT) control group.PATIENTS AND METHODSAll colorectal cancer patients tested for BRAF mutation, from October 2010 to November 2014 were identified. BRAF-MT mCRC cases were compared with an age and sex-matched BRAF-WT control group. Clinicopathological data were collected and survival calculated using the Kaplan-Meier method and comparisons made using Cox regression.RESULTSForty-three of 503 patients (8.5%) tested had BRAF-MT mCRC and were compared with 88 BRAF-WT controls. Median overall survival (mOS) was 18.2 months for BRAF-MT and 41.1 months for BRAF-WT mCRC patients (hazard ratio, 2.74; 95% confidence interval, 1.60-4.70; P < .001). Progression-free survival for BRAF-MT and WT patients, respectively, was: 8.1 months versus 9.2 months (P = .571) first-line, 5.5 months versus 8.3 months (P = .074) second-line, and 1.8 months versus 5.6 months (P = .074) third-line. Treatment using sequential fluoropyrimidine-based doublet chemotherapy was similar between both groups. Anti-epidermal growth factor receptor (EGFR) therapy was mainly given third-line with progressive disease in 90% (n = 9 of 10) of BRAF-MT patients at first restaging.CONCLUSIONIn this case-control study, the poor mOS of BRAF-MT mCRC was associated with reduced treatment benefit beyond first-line. Sequential doublet chemotherapy remains a reasonable option in appropriately selected patients. BRAF-MT patients did not benefit from anti-EGFR therapy in this study. Recruitment to clinical trials is recommended to improve outcomes in BRAF-MT mCRC.",

keywords = "Journal Article",

author = "Hamzeh Kayhanian and Emily Goode and Francesco Sclafani and Ang, {Joo Ern} and Marco Gerlinger and {Gonzalez de Castro}, David and Scott Shepherd and Clare Peckitt and Sheela Rao and David Watkins and Ian Chau and David Cunningham and Naureen Starling",

note = "Copyright {\textcopyright} 2017. Published by Elsevier Inc.",

year = "2018",

month = mar,

doi = "10.1016/j.clcc.2017.10.006",

language = "English",

volume = "17",

journal = "Clinical colorectal cancer",

issn = "1533-0028",

publisher = "Elsevier B.V.",

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Kayhanian, H, Goode, E, Sclafani, F, Ang, JE, Gerlinger, M, Gonzalez de Castro, D, Shepherd, S, Peckitt, C, Rao, S, Watkins, D, Chau, I, Cunningham, D & Starling, N 2018, 'Treatment and Survival Outcome of BRAF-Mutated Metastatic Colorectal Cancer A Retrospective Matched Case-Control Study', Clinical colorectal cancer, vol. 17, no. 1. https://doi.org/10.1016/j.clcc.2017.10.006

TY - JOUR

T1 - Treatment and Survival Outcome of BRAF-Mutated Metastatic Colorectal Cancer A Retrospective Matched Case-Control Study

AU - Kayhanian, Hamzeh

AU - Goode, Emily

AU - Sclafani, Francesco

AU - Ang, Joo Ern

AU - Gerlinger, Marco

AU - Gonzalez de Castro, David

AU - Shepherd, Scott

AU - Peckitt, Clare

AU - Rao, Sheela

AU - Watkins, David

AU - Chau, Ian

AU - Cunningham, David

AU - Starling, Naureen

PY - 2018/3

Y1 - 2018/3

N2 - BACKGROUNDSomatic v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutation, present in approximately 10% of metastatic colorectal cancer (mCRC) cases, is associated with poor prognosis. Patient outcome outside of clinical trials has only been reported in small series. We report real-world data on treatment and survival for BRAF-mutated (MT) patients at a single tertiary center, compared with a matched BRAF wild type (WT) control group.PATIENTS AND METHODSAll colorectal cancer patients tested for BRAF mutation, from October 2010 to November 2014 were identified. BRAF-MT mCRC cases were compared with an age and sex-matched BRAF-WT control group. Clinicopathological data were collected and survival calculated using the Kaplan-Meier method and comparisons made using Cox regression.RESULTSForty-three of 503 patients (8.5%) tested had BRAF-MT mCRC and were compared with 88 BRAF-WT controls. Median overall survival (mOS) was 18.2 months for BRAF-MT and 41.1 months for BRAF-WT mCRC patients (hazard ratio, 2.74; 95% confidence interval, 1.60-4.70; P < .001). Progression-free survival for BRAF-MT and WT patients, respectively, was: 8.1 months versus 9.2 months (P = .571) first-line, 5.5 months versus 8.3 months (P = .074) second-line, and 1.8 months versus 5.6 months (P = .074) third-line. Treatment using sequential fluoropyrimidine-based doublet chemotherapy was similar between both groups. Anti-epidermal growth factor receptor (EGFR) therapy was mainly given third-line with progressive disease in 90% (n = 9 of 10) of BRAF-MT patients at first restaging.CONCLUSIONIn this case-control study, the poor mOS of BRAF-MT mCRC was associated with reduced treatment benefit beyond first-line. Sequential doublet chemotherapy remains a reasonable option in appropriately selected patients. BRAF-MT patients did not benefit from anti-EGFR therapy in this study. Recruitment to clinical trials is recommended to improve outcomes in BRAF-MT mCRC.

AB - BACKGROUNDSomatic v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutation, present in approximately 10% of metastatic colorectal cancer (mCRC) cases, is associated with poor prognosis. Patient outcome outside of clinical trials has only been reported in small series. We report real-world data on treatment and survival for BRAF-mutated (MT) patients at a single tertiary center, compared with a matched BRAF wild type (WT) control group.PATIENTS AND METHODSAll colorectal cancer patients tested for BRAF mutation, from October 2010 to November 2014 were identified. BRAF-MT mCRC cases were compared with an age and sex-matched BRAF-WT control group. Clinicopathological data were collected and survival calculated using the Kaplan-Meier method and comparisons made using Cox regression.RESULTSForty-three of 503 patients (8.5%) tested had BRAF-MT mCRC and were compared with 88 BRAF-WT controls. Median overall survival (mOS) was 18.2 months for BRAF-MT and 41.1 months for BRAF-WT mCRC patients (hazard ratio, 2.74; 95% confidence interval, 1.60-4.70; P < .001). Progression-free survival for BRAF-MT and WT patients, respectively, was: 8.1 months versus 9.2 months (P = .571) first-line, 5.5 months versus 8.3 months (P = .074) second-line, and 1.8 months versus 5.6 months (P = .074) third-line. Treatment using sequential fluoropyrimidine-based doublet chemotherapy was similar between both groups. Anti-epidermal growth factor receptor (EGFR) therapy was mainly given third-line with progressive disease in 90% (n = 9 of 10) of BRAF-MT patients at first restaging.CONCLUSIONIn this case-control study, the poor mOS of BRAF-MT mCRC was associated with reduced treatment benefit beyond first-line. Sequential doublet chemotherapy remains a reasonable option in appropriately selected patients. BRAF-MT patients did not benefit from anti-EGFR therapy in this study. Recruitment to clinical trials is recommended to improve outcomes in BRAF-MT mCRC.

KW - Journal Article

U2 - 10.1016/j.clcc.2017.10.006

DO - 10.1016/j.clcc.2017.10.006

M3 - Article

C2 - 29129559

SN - 1533-0028

VL - 17

JO - Clinical colorectal cancer

JF - Clinical colorectal cancer

IS - 1

ER -

Treatment and Survival Outcome of BRAF-Mutated Metastatic Colorectal Cancer A Retrospective Matched Case-Control Study

Abstract

Keywords

UN SDGs

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