BRAFV600E Mutations Arising from a Left-Side Primary in Metastatic Colorectal Cancer: Are They a Distinct Subset?
Journal
Targeted oncology
ISSN: 1776-260X
Titre abrégé: Target Oncol
Pays: France
ID NLM: 101270595
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
accepted:
22
01
2021
pubmed:
19
2
2021
medline:
3
11
2021
entrez:
18
2
2021
Statut:
ppublish
Résumé
B-Raf proto-oncogene (BRAF)-V600E mutations (BRAFmt) in colorectal cancer (CRC) predominantly occur in right-side (RS) primaries. In metastatic CRC (mCRC), there is substantial overlap between the reported features of BRAFmt and of an RS primary. To explore the significance of BRAFmt in a left-side (LS) primary, we analysed data from a multi-site mCRC registry. Tumours distal to the splenic flexure were considered LS. Of 3380 patients enrolled from June 2009 to June 2020, 214 (13%) of 1657 with known status were BRAFmt: 127 (24%) of 524 RS and 87 (8%) of 1133 LS. LS versus RS BRAFmt were younger (mean 59.5 vs. 65.1 years; p = 0.01), whereas sex (48 vs. 59% female; p = 0.13), mismatch repair-deficiency (dMMR) (16 vs. 21%; p = 0.47), and overall survival (OS) (median 15.1 vs. 17.7 months; p = 0.98) were similar. LS BRAFmt versus LS BRAF wildtype (wt) were of similar age (59.5 vs. 61.3 years; p = 0.28) with more females (48 vs. 37%; p = 0.04), more dMMR (16 vs. 1%; p < 0.0001), and inferior OS (median 15.1 vs. 36.6 months; p < 0.0001). Initial treatment with chemotherapy plus an epidermal growth factor receptor inhibitor produced median progression-free survival (PFS) of 4.3 versus 12.3 months (p = 0.20) for LS BRAFmt (n = 9) versus LS BRAFwt (n = 104). Initial chemotherapy and bevacizumab produced a median PFS of 7.6 versus 11.6 months (p = 0.02) for LS BRAFmt (n = 36) versus LS BRAFwt (n = 438), respectively. LS BRAFmt cancers share many features with RS BRAFmt cancers, including poor survival outcomes. Mature data on the activity of BRAF-targeted therapies in the first-line setting are eagerly awaited.
Sections du résumé
BACKGROUND
B-Raf proto-oncogene (BRAF)-V600E mutations (BRAFmt) in colorectal cancer (CRC) predominantly occur in right-side (RS) primaries. In metastatic CRC (mCRC), there is substantial overlap between the reported features of BRAFmt and of an RS primary.
OBJECTIVES
To explore the significance of BRAFmt in a left-side (LS) primary, we analysed data from a multi-site mCRC registry. Tumours distal to the splenic flexure were considered LS.
RESULTS
Of 3380 patients enrolled from June 2009 to June 2020, 214 (13%) of 1657 with known status were BRAFmt: 127 (24%) of 524 RS and 87 (8%) of 1133 LS. LS versus RS BRAFmt were younger (mean 59.5 vs. 65.1 years; p = 0.01), whereas sex (48 vs. 59% female; p = 0.13), mismatch repair-deficiency (dMMR) (16 vs. 21%; p = 0.47), and overall survival (OS) (median 15.1 vs. 17.7 months; p = 0.98) were similar. LS BRAFmt versus LS BRAF wildtype (wt) were of similar age (59.5 vs. 61.3 years; p = 0.28) with more females (48 vs. 37%; p = 0.04), more dMMR (16 vs. 1%; p < 0.0001), and inferior OS (median 15.1 vs. 36.6 months; p < 0.0001). Initial treatment with chemotherapy plus an epidermal growth factor receptor inhibitor produced median progression-free survival (PFS) of 4.3 versus 12.3 months (p = 0.20) for LS BRAFmt (n = 9) versus LS BRAFwt (n = 104). Initial chemotherapy and bevacizumab produced a median PFS of 7.6 versus 11.6 months (p = 0.02) for LS BRAFmt (n = 36) versus LS BRAFwt (n = 438), respectively.
CONCLUSION
LS BRAFmt cancers share many features with RS BRAFmt cancers, including poor survival outcomes. Mature data on the activity of BRAF-targeted therapies in the first-line setting are eagerly awaited.
Identifiants
pubmed: 33599905
doi: 10.1007/s11523-021-00793-7
pii: 10.1007/s11523-021-00793-7
doi:
Substances chimiques
MAS1 protein, human
0
Proto-Oncogene Mas
0
BRAF protein, human
EC 2.7.11.1
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
227-236Références
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424. https://doi.org/10.3322/caac.21492 .
doi: 10.3322/caac.21492
Howlader N, Noone AM, Krapcho M, Miller D, Brest A, Yu M, et al. SEER cancer statistics review, 1975–2017, National Cancer Institute. Bethesda, MD. https://seer.cancer.gov/csr/1975_2017/ based on November 2019 SEER data submission, posted to the SEER web site, April 2020.
Tejpar S, Stintzing S, Ciardiello F, Tabernero J, Van Cutsem E, Beier F, et al. Prognostic and predictive relevance of primary tumor location in patients with RAS wild-type metastatic colorectal cancer. JAMA Oncol. 2017;3(2):194. https://doi.org/10.1001/jamaoncol.2016.3797 .
doi: 10.1001/jamaoncol.2016.3797
pubmed: 27722750
pmcid: 7505121
Tie J, Gibbs P, Lipton L, Christie M, Jorissen R, Burgess A, et al. Optimizing targeted therapeutic development: analysis of a colorectal cancer patient population with the BRAFV600E mutation. Int J Cancer. 2011;128(9):2075–84.
doi: 10.1002/ijc.25555
Kalady M, DeJulius K, Sanchez J, Jarrar A, Liu X, Manilic E, et al. BRAF mutations in colorectal cancer are associated with distinct clinical characteristics and worse prognosis. Dis Colon Rectum. 2012;55(2):128–33. https://doi.org/10.1097/dcr.0b013e31823c08b3 .
doi: 10.1097/dcr.0b013e31823c08b3
pubmed: 22228154
Scartozzi M, Giampieri R, Aprile G, Iacono D, Santini D, dell’Aquila E, et al. The distinctive molecular, pathological and clinical characteristics of BRAF-mutant colorectal tumors. Expert Rev Mol Diagn. 2015;15(8):979–87. https://doi.org/10.1586/14737159.2015.1047346 .
doi: 10.1586/14737159.2015.1047346
pubmed: 25975986
Bokemeyer C, Van Cutsem E, Rougier P, Ciardiello F, Heeger S, Schlichting M, et al. Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer: pooled analysis of the CRYSTAL and OPUS randomised clinical trials. Eur J Cancer. 2012;48(10):1466–75.
doi: 10.1016/j.ejca.2012.02.057
Mendis S, Beck S, Lee B, Lee M, Wong R, Kosmider S, et al. Right versus left sided metastatic colorectal cancer: teasing out clinicopathologic drivers of disparity in survival. Asia Pac J Clin Oncol. 2019;15(3):136–43. https://doi.org/10.1111/ajco.13135 .
doi: 10.1111/ajco.13135
pubmed: 30761750
Bylsma LC, Gillezeau C, Garawin TA, Kelsha MA, Fryzek JP, Sangare L, et al. Prevalence of RAS and BRAF mutations in metastatic colorectal cancer patients by tumor sidedness: a systematic review and meta-analysis. Cancer Med. 2020;9(3):1044–57. https://doi.org/10.1002/cam4.2747 .
doi: 10.1002/cam4.2747
pubmed: 31856410
Suidan R, Leitao M, Zivanovic O, Gardner G, Long Roche K, Sonoda Y, et al. Predictive value of the Age-Adjusted Charlson Comorbidity Index on perioperative complications and survival in patients undergoing primary debulking surgery for advanced epithelial ovarian cancer. Gynecol Oncol. 2015;138(2):246–51. https://doi.org/10.1016/j.ygyno.2015.05.034 .
doi: 10.1016/j.ygyno.2015.05.034
pubmed: 26037900
pmcid: 4972341
Baran B, Mert Ozupek N, Yerli Tetik N, Acar E, Bekcioglu O, Baskin Y. Difference between left-sided and right-sided colorectal cancer: a focused review of literature. Gastroenterol Res. 2018;11(4):264–73. https://doi.org/10.14740/gr1062w .
doi: 10.14740/gr1062w
Rowland A, Dias M, Wiese M, Kichenadasse G, McKinnon R, Karapetis C, Sorich M. Meta-analysis of BRAF mutation as a predictive biomarker of benefit from anti-EGFR monoclonal antibody therapy for RAS wild-type metastatic colorectal cancer. Br J Cancer. 2015;112(12):1888–94. https://doi.org/10.1038/bjc.2015.173 .
doi: 10.1038/bjc.2015.173
pubmed: 4580381
pmcid: 4580381
Pietrantonio F, Petrelli F, Coinu A, Di Bartolomeo M, Borgonovo K, Maggi C, et al. Predictive role of BRAF mutations in patients with advanced colorectal cancer receiving cetuximab and panitumumab: a meta-analysis. Eur J Cancer. 2015;51(5):587–94. https://doi.org/10.1016/j.ejca.2015.01.054 .
doi: 10.1016/j.ejca.2015.01.054
Di Nicolantonio F, Martini M, Molinari F, Sartore-Bianchi A, Arena S, Saletti P, et al. Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol. 2008;26:5705–12.
doi: 10.1200/JCO.2008.18.0786
Mao C, Liao R, Qiu L, Wang X, Ding H, Chen Q, et al. BRAF V600E mutation and resistance to anti-EGFR monoclonal antibodies in patients with metastatic colorectal cancer: a meta-analysis. Mol Biol Rep. 2011;38:2219–23. https://doi.org/10.1007/s11033-010-0351-4 .
doi: 10.1007/s11033-010-0351-4
pubmed: 20857202
Falcone A, Ricci S, Brunetti I, Pfanner E, Allegrini G, Barbara C, et al. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol. 2007;25(13):1670–6.
doi: 10.1200/JCO.2006.09.0928
Loupakis F, Cremolini C, Masi G, Lonardi S, Zagonel V, Salvatore L, et al. Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer. N Engl J Med. 2014;371(17):1609–18.
doi: 10.1056/NEJMoa1403108
Cremolini C, Loupakis F, Antoniotti C, Lupi C, Sensi E, Lonardi S, et al. FOLFOXIRI plus bevacizumab (bev) versus FOLFIRI plus bev as first-line treatment of metastatic colorectal cancer (mCRC): Updated survival results of the phase III TRIBE trial by the GONO group. Lancet Oncol. 2015;16(13):1306–15. https://doi.org/10.1016/S1470-2045(15)00122-9 .
doi: 10.1016/S1470-2045(15)00122-9
pubmed: 26338525
Kopetz S, Grothey A, Yaeger R, Van Cutsem E, Desai J, Yoshino T, et al. Encorafenib, binimetinib, and cetuximab in BRAF V600E-mutated colorectal cancer. N Engl J Med. 2019;381(17):1632–43. https://doi.org/10.1056/NEJMoa1908075 .
doi: 10.1056/NEJMoa1908075
pubmed: 31566309
Kopetz S, Mcdonough SL, Lenz HJ, Magliocco AM, Atreya CE, Diaz LA, et al. Randomized trial of irinotecan and cetuximab with or without vemurafenib in BRAF-mutant metastatic colorectal cancer (SWOG S1406). J Clin Oncol. 2017;35(15_Suppl):3505.
doi: 10.1200/JCO.2017.35.15_suppl.3505
Grothey A, Tabernero J, Taieb J, Yaeger R, Yoshino T, Maiello E, et al. LBA-5 ANCHOR CRC: a single-arm, phase 2 study of encorafenib, binimetinib plus cetuximab in previously untreated BRAF V600E-mutant metastatic colorectal cancer. Ann Oncol. 2020;31:S242–3.
doi: 10.1016/j.annonc.2020.04.080
Ducreux M, Chamseddine A, Laurent-Puig P, Smolenschi C, Hollebecque A, Dartigues P, et al. Molecular targeted therapy of BRAF-mutant colorectal cancer. Ther Adv Med Oncol. 2019;11:1758835919856494.
doi: 10.1177/1758835919856494
Andre T, Shiu K-K, Kim TW, Jensen BV, Jensen LH, Punt C, et al. (2020) Pembrolizumab vs. chemotherapy for microsatellite instability-high/mismatch repair deficient metastatic colorectal cancer: The phase 3 KEYNOTE-177 study. J Clin Oncol 38(18_suppl):LBA4. https://doi.org/10.1200/JCO.2020.38.18_suppl.LBA4
Seppälä TT, Böhm JP, Friman M, Lahtinen L, Väyrynen VM, Liipo TK, et al. Combination of microsatellite instability and BRAF mutation status for subtyping colorectal cancer. Br J Cancer. 2015;112(12):1966–75. https://doi.org/10.1038/bjc.2015.160 .
doi: 10.1038/bjc.2015.160
pubmed: 25973534
pmcid: 4580394
Atreya CE, Greene C, McWhirter RM, Ikram NS, Allen IE, Van Loon K, et al. Differential radiographic appearance of BRAF V600E-mutant metastatic colorectal cancer in patients matched by primary tumor location. J Natl Compr Cancer Netw. 2016;14(12):1536–43. https://doi.org/10.6004/jnccn.2016.0165 .
doi: 10.6004/jnccn.2016.0165