All currencies in US Dollar
This portion of the NCCN Guidelines for Colon Cancer focuses on the use of systemic therapy in metastatic disease. Considerations for treatment selection among 32 different monotherapies and combination regimens in up to 7 lines of therapy have included treatment history, extent of disease, goals of treatment, the efficacy and toxicity profiles of the regimens, KRAS/NRAS mutational status, and patient comorbidities and preferences. Location of the primary tumor, the BRAF mutation status, and tumor microsatellite stability should also be considered in treatment decisions.
SiegelRLMillerKDJemalA. Cancer statistics, 2016. CA Cancer J Clin2016;66:7–30.
ChengLEngCNiemanLZ. Trends in colorectal cancer incidence by anatomic site and disease stage in the United States from 1976 to 2005. Am J Clin Oncol2011;34:573–580.
HenleySJSinghSDKingJ. Invasive cancer incidence and survival—United States, 2011. MMWR Morb Mortal Wkly Rep2015;64:237–242.
SiegelRWardEBrawleyOJemalA. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin2011;61:212–236.
BaileyCEHuCYYouYN. Increasing disparities in the age-related incidences of colon and rectal cancers in the United States, 1975-2010. JAMA Surg2014:1–6.
AminMBGreeneFLEdgeS eds. AJCC Cancer Staging Manual8th ed.New York: Springer; 2016.
AmadoRGWolfMPeetersM. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol2008;26:1626–1634.
AndreTLouvetCMaindrault-GoebelF. CPT-11 (irinotecan) addition to bimonthly, high-dose leucovorin and bolus and continuous-infusion 5-fluorouracil (FOLFIRI) for pretreated metastatic colorectal cancer. GERCOR. Eur J Cancer1999;35:1343–1347.
BartlettDLBerlinJLauwersGY. Chemotherapy and regional therapy of hepatic colorectal metastases: expert consensus statement. Ann Surg Oncol2006;13:1284–1292.
BurokerTRO'ConnellMJWieandHS. Randomized comparison of two schedules of fluorouracil and leucovorin in the treatment of advanced colorectal cancer. J Clin Oncol1994;12:14–20.
CassidyJClarkeSDiaz-RubioE. Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol2008;26:2006–2012.
CheesemanSLJoelSPChesterJD. A ‘modified de Gramont’ regimen of fluorouracil, alone and with oxaliplatin, for advanced colorectal cancer. Br J Cancer2002;87:393–399.
ColucciGGebbiaVPaolettiG. Phase III randomized trial of FOLFIRI versus FOLFOX4 in the treatment of advanced colorectal cancer: a multicenter study of the Gruppo Oncologico Dell'Italia Meridionale. J Clin Oncol2005;23:4866–4875.
CunninghamDHumbletYSienaS. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med2004;351:337–345.
CunninghamDPyrhonenSJamesRD. Randomised trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancer. Lancet1998;352:1413–1418.
de GramontABossetJFMilanC. Randomized trial comparing monthly low-dose leucovorin and fluorouracil bolus with bimonthly high-dose leucovorin and fluorouracil bolus plus continuous infusion for advanced colorectal cancer: a French intergroup study. J Clin Oncol1997;15:808–815.
de GramontAFigerASeymourM. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol2000;18:2938–2947.
DelaunoitTGoldbergRMSargentDJ. Mortality associated with daily bolus 5-fluorouracil/leucovorin administered in combination with either irinotecan or oxaliplatin: results from Intergroup trial N9741. Cancer2004;101:2170–2176.
DouillardJYCunninghamDRothAD. Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet2000;355:1041–1047.
DouillardJYSienaSCassidyJ. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol2010;28:4697–4705.
FalconeARicciSBrunettiI. 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 Oncol2007;25:1670–1676.
FuchsCSMooreMRHarkerG. Phase III comparison of two irinotecan dosing regimens in second-line therapy of metastatic colorectal cancer. J Clin Oncol2003;21:807–814.
GiantonioBJCatalanoPJMeropolNJ. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol2007;25:1539–1544.
GoldbergRM. Therapy for metastatic colorectal cancer. Oncologist2006;11:981–987.
GoldbergRMRothenbergMLVan CutsemE. The continuum of care: a paradigm for the management of metastatic colorectal cancer. Oncologist2007;12:38–50.
GoldbergRMSargentDJMortonRF. A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol2004;22:23–30.
GrotheyAVan CutsemESobreroA. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet2013;381:303–312.
HallerDGRothenbergMLWongAO. Oxaliplatin plus irinotecan compared with irinotecan alone as second-line treatment after single-agent fluoropyrimidine therapy for metastatic colorectal carcinoma. J Clin Oncol2008;26:4544–4550.
HurwitzHIFehrenbacherLHainsworthJD. Bevacizumab in combination with fluorouracil and leucovorin: an active regimen for first-line metastatic colorectal cancer. J Clin Oncol2005;23:3502–3508.
JagerEHeikeMBernhardH. Weekly high-dose leucovorin versus low-dose leucovorin combined with fluorouracil in advanced colorectal cancer: results of a randomized multicenter trial. Study Group for Palliative Treatment of Metastatic Colorectal Cancer Study Protocol 1. J Clin Oncol1996;14:2274–2279.
KabbinavarFFHambletonJMassRD. Combined analysis of efficacy: the addition of bevacizumab to fluorouracil/leucovorin improves survival for patients with metastatic colorectal cancer. J Clin Oncol2005;23:3706–3712.
KellyHGoldbergRM. Systemic therapy for metastatic colorectal cancer: current options, current evidence. J Clin Oncol2005;23:4553–4560.
KohneCHHofheinzRMineurL. First-line panitumumab plus irinotecan/5-fluorouracil/leucovorin treatment in patients with metastatic colorectal cancer. J Cancer Res Clin Oncol2012;138:65–72.
Maindrault-GoebelFLouvetCAndreT. Oxaliplatin added to the simplified bimonthly leucovorin and 5-fluorouracil regimen as second-line therapy for metastatic colorectal cancer (FOLFOX6). GERCOR. Eur J Cancer1999;35:1338–1342.
MayerRJVan CutsemEFalconeA. Randomized trial of TAS-102 for refractory metastatic colorectal cancer. N Engl J Med2015;372:1909–1919.
PeetersMPriceTJCervantesA. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol2010;28:4706–4713.
PetrelliNHerreraLRustumY. A prospective randomized trial of 5-fluorouracil versus 5-fluorouracil and high-dose leucovorin versus 5-fluorouracil and methotrexate in previously untreated patients with advanced colorectal carcinoma. J Clin Oncol1987;5:1559–1565.
ReidyDLChungKYTimoneyJP. Bevacizumab 5 mg/kg can be infused safely over 10 minutes. J Clin Oncol2007;25:2691–2695.
SaltzLBClarkeSDiaz-RubioE. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol2008;26:2013–2019.
SouglakosJAndroulakisNSyrigosK. FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin and irinotecan) vs FOLFIRI (folinic acid, 5-fluorouracil and irinotecan) as first-line treatment in metastatic colorectal cancer (MCC): a multicentre randomised phase III trial from the Hellenic Oncology Research Group (HORG). Br J Cancer2006;94:798–805.
TolJKoopmanMCatsA. Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N Engl J Med2009;360:563–572.
Van CutsemE. Challenges in the use of epidermal growth factor receptor inhibitors in colorectal cancer. Oncologist2006;11:1010–1017.
Van CutsemEHoffPMHarperP. Oral capecitabine vs intravenous 5-fluorouracil and leucovorin: integrated efficacy data and novel analyses from two large, randomised, phase III trials. Br J Cancer2004;90:1190–1197.
Van CutsemEKohneCHHitreE. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med2009;360:1408–1417.
Van CutsemEPeetersMSienaS. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol2007;25:1658–1664.
Van CutsemETwelvesCCassidyJ. Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. J Clin Oncol2001;19:4097–4106.
Van CutsemETaberneroJLakomyR. Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. J Clin Oncol2012;30:3499–3506.
WolmarkNRocketteHFisherB. The benefit of leucovorin-modulated fluorouracil as postoperative adjuvant therapy for primary colon cancer: results from National Surgical Adjuvant Breast and Bowel Project protocol C-03. J Clin Oncol1993;11:1879–1887.
LentzFTranAReyE. Pharmacogenomics of fluorouracil, irinotecan, and oxaliplatin in hepatic metastases of colorectal cancer: clinical implications. Am J Pharmacogenomics2005;5:21–33.
O'DwyerPJ. The present and future of angiogenesis-directed treatments of colorectal cancer. Oncologist2006;11:992–998.
RaymondEFaivreSWoynarowskiJMChaneySG. Oxaliplatin: mechanism of action and antineoplastic activity. Semin Oncol1998;25:4–12.
RothenbergMLBlankeCD. Topoisomerase I inhibitors in the treatment of colorectal cancer. Semin Oncol1999;26:632–639.
TournigandCAndreTAchilleE. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol2004;22:229–237.
CassidyJTaberneroJTwelvesC. XELOX (capecitabine plus oxaliplatin): active first-line therapy for patients with metastatic colorectal cancer. J Clin Oncol2004;22:2084–2091.
PorschenRArkenauHTKubickaS. Phase III study of capecitabine plus oxaliplatin compared with fluorouracil and leucovorin plus oxaliplatin in metastatic colorectal cancer: a final report of the AIO Colorectal Study Group. J Clin Oncol2007;25:4217–4223.
KirsteinMMLangeAPrenzlerA. Targeted therapies in metastatic colorectal cancer: a systematic review and assessment of currently available data. Oncologist2014;19:1156–1168.
DucreuxMMalkaDMendiboureJ. Sequential versus combination chemotherapy for the treatment of advanced colorectal cancer (FFCD 2000-05): an open-label, randomised, phase 3 trial. Lancet Oncol2011;12:1032–1044.
KoopmanMAntoniniNFDoumaJ. Sequential versus combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in advanced colorectal cancer (CAIRO): a phase III randomised controlled trial. Lancet2007;370:135–142.
SeymourMTMaughanTSLedermannJA. Different strategies of sequential and combination chemotherapy for patients with poor prognosis advanced colorectal cancer (MRC FOCUS): a randomised controlled trial. Lancet2007;370:143–152.
GrotheyASargentDGoldbergRMSchmollHJ. Survival of patients with advanced colorectal cancer improves with the availability of fluorouracil-leucovorin, irinotecan, and oxaliplatin in the course of treatment. J Clin Oncol2004;22:1209–1214.
SargentDJKohneCHSanoffHK. Pooled safety and efficacy analysis examining the effect of performance status on outcomes in nine first-line treatment trials using individual data from patients with metastatic colorectal cancer. J Clin Oncol2009;27:1948–1955.
SimkensLHvan TinterenHMayA. Maintenance treatment with capecitabine and bevacizumab in metastatic colorectal cancer (CAIRO3): a phase 3 randomised controlled trial of the Dutch Colorectal Cancer Group. Lancet2015;385:1843–1852.
Hegewisch-BeckerSGraevenULerchenmullerCA. Maintenance strategies after first-line oxaliplatin plus fluoropyrimidine plus bevacizumab for patients with metastatic colorectal cancer (AIO 0207): a randomised, non-inferiority, open-label, phase 3 trial. Lancet Oncol2015;16:1355–1369.
KoeberleDBetticherDCvon MoosR. Bevacizumab continuation versus no continuation after first-line chemotherapy plus bevacizumab in patients with metastatic colorectal cancer: a randomized phase III non-inferiority trial (SAKK 41/06). Ann Oncol2015;26:709–714.
TournigandCChibaudelBSamsonB. Bevacizumab with or without erlotinib as maintenance therapy in patients with metastatic colorectal cancer (GERCOR DREAM; OPTIMOX3): a randomised, open-label, phase 3 trial. Lancet Oncol2015;16:1493–1505.
HagmanHFrodinJEBerglundA. A randomized study of KRAS-guided maintenance therapy with bevacizumab, erlotinib or metronomic capecitabine after first-line induction treatment of metastatic colorectal cancer: the Nordic ACT2 trial. Ann Oncol2016;27:140–147.
XuWGongYKuangM. Survival benefit and safety of bevacizumab in combination with erlotinib as maintenance therapy in patients with metastatic colorectal cancer: a meta-analysis. Clin Drug Investig2017;37:155–165.
LuoHYLiYHWangW. Single-agent capecitabine as maintenance therapy after induction of XELOX (or FOLFOX) in first-line treatment of metastatic colorectal cancer: randomized clinical trial of efficacy and safety. Ann Oncol2016;27:1074–1081.
AVASTIN [package insert]. South San Francisco, CA: Genentech, Inc.; 2015.
HurwitzHFehrenbacherLNovotnyW. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med2004;350:2335–2342.
KabbinavarFHurwitzHIFehrenbacherL. Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol2003;21:60–65.
KabbinavarFFSchulzJMcCleodM. Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: results of a randomized phase II trial. J Clin Oncol2005;23:3697–3705.
PetrelliFBorgonovoKCabidduM. FOLFIRI-bevacizumab as first-line chemotherapy in 3500 patients with advanced colorectal cancer: a pooled analysis of 29 published trials. Clin Colorectal Cancer2013;12:145–151.
HurwitzHIBekaii-SaabTSBendellJC. Safety and effectiveness of bevacizumab treatment for metastatic colorectal cancer: final results from the Avastin((R)) Registry - Investigation of Effectiveness and Safety (ARIES) observational cohort study. Clin Oncol (R Coll Radiol)2014;26:323–332.
Fourrier-ReglatASmithDRouyerM. Survival outcomes of bevacizumab in first-line metastatic colorectal cancer in a real-life setting: results of the ETNA cohort. Target Oncol2014;9:311–319.
BotrelTEClarkLGPaladiniLClarkOA. Efficacy and safety of bevacizumab plus chemotherapy compared to chemotherapy alone in previously untreated advanced or metastatic colorectal cancer: a systematic review and meta-analysis. BMC Cancer2016;16:677.
CaoYTanAGaoF. A meta-analysis of randomized controlled trials comparing chemotherapy plus bevacizumab with chemotherapy alone in metastatic colorectal cancer. Int J Colorectal Dis2009;24:677–685.
HuWXuWLiaoXHeH. Bevacizumab in combination with first-line chemotherapy in patients with metastatic colorectal cancer: a meta-analysis. Minerva Chir2015;70:451–458.
HurwitzHITebbuttNCKabbinavarF. Efficacy and safety of bevacizumab in metastatic colorectal cancer: pooled analysis from seven randomized controlled trials. Oncologist2013;18:1004–1012.
LoupakisFBriaEVaccaroV. Magnitude of benefit of the addition of bevacizumab to first-line chemotherapy for metastatic colorectal cancer: meta-analysis of randomized clinical trials. J Exp Clin Cancer Res2010;29:58.
LvCWuSZhengD. The efficacy of additional bevacizumab to cytotoxic chemotherapy regimens for the treatment of colorectal cancer: an updated meta-analysis for randomized trials. Cancer Biother Radiopharm2013;28:501–509.
QuCYZhengYZhouM. Value of bevacizumab in treatment of colorectal cancer: a meta-analysis. World J Gastroenterol2015;21:5072–5080.
WelchSSpithoffKRumbleRBMarounJ. Bevacizumab combined with chemotherapy for patients with advanced colorectal cancer: a systematic review. Ann Oncol2010;21:1152–1162.
ZhangGZhouXLinC. Efficacy of chemotherapy plus bevacizumab as first-line therapy in patients with metastatic colorectal cancer: a meta-analysis and up-date. Int J Clin Exp Med2015;8:1434–1445.
MacedoLTda Costa LimaABSasseAD. Addition of bevacizumab to first-line chemotherapy in advanced colorectal cancer: a systematic review and meta-analysis, with emphasis on chemotherapy subgroups. BMC Cancer2012;12:89.
MeyerhardtJALiLSanoffHK. Effectiveness of bevacizumab with first-line combination chemotherapy for Medicare patients with stage IV colorectal cancer. J Clin Oncol2012;30:608–615.
HartmannHMullerJMarschnerN. Is there a difference in demography and clinical characteristics in patients treated with and without bevacizumab?J Clin Oncol2012;30:3317–3318; author reply 3318.
HurwitzHILymanGH. Registries and randomized trials in assessing the effects of bevacizumab in colorectal cancer: is there a common theme?J Clin Oncol2012;30:580–581.
AllegraCJYothersGO'ConnellMJ. Phase III trial assessing bevacizumab in stages II and III carcinoma of the colon: results of NSABP protocol C-08. J Clin Oncol2011;29:11–16.
de GramontAVan CutsemESchmollHJ. Bevacizumab plus oxaliplatin-based chemotherapy as adjuvant treatment for colon cancer (AVANT): a phase 3 randomised controlled trial. Lancet Oncol2012;13:1225–1233.
RanpuraVHapaniSWuS. Treatment-related mortality with bevacizumab in cancer patients: a meta-analysis. JAMA2011;305:487–494.
HurwitzHISaltzLBVan CutsemE. Venous thromboembolic events with chemotherapy plus bevacizumab: a pooled analysis of patients in randomized phase II and III studies. J Clin Oncol2011;29:1757–1764.
DaiFShuLBianY. Safety of bevacizumab in treating metastatic colorectal cancer: a systematic review and meta-analysis of all randomized clinical trials. Clin Drug Investig2013;33:779–788.
HochsterHSHartLLRamanathanRK. Safety and efficacy of oxaliplatin and fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer: results of the TREE Study. J Clin Oncol2008;26:3523–3529.
ScappaticciFAFehrenbacherLCartwrightT. Surgical wound healing complications in metastatic colorectal cancer patients treated with bevacizumab. J Surg Oncol2005;91:173–180.
CannistraSAMatulonisUAPensonRT. Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. J Clin Oncol2007;25:5180–5186.
GruenbergerBTamandlDSchuellerJ. Bevacizumab, capecitabine, and oxaliplatin as neoadjuvant therapy for patients with potentially curable metastatic colorectal cancer. J Clin Oncol2008;26:1830–1835.
ReddySKMorseMAHurwitzHI. Addition of bevacizumab to irinotecan- and oxaliplatin-based preoperative chemotherapy regimens does not increase morbidity after resection of colorectal liver metastases. J Am Coll Surg2008;206:96–9106.
MilesDHarbeckNEscudierB. Disease course patterns after discontinuation of bevacizumab: pooled analysis of randomized phase III trials. J Clin Oncol2011;29:83–88.
MilesDW. Reply to P. Potemski. J Clin Oncol2011;29:e386.
PotemskiP. Is the postprogression survival time really not shortened in the bevacizumab-containing arms of phase III clinical trials?J Clin Oncol2011;29:e384–385.
Cetuximab [package insert]. Branchburg, NJ: ImClone Systems Incorporated; 2015.
Vectibix [package insert]. Thousand Oaks, CA: Amgen Inc.; 2015.
PietrantonioFCremoliniCPetrelliF. First-line anti-EGFR monoclonal antibodies in panRAS wild-type metastatic colorectal cancer: a systematic review and meta-analysis. Crit Rev Oncol Hematol2015;96:156–166.
SorichMJWieseMDRowlandA. Extended RAS mutations and anti-EGFR monoclonal antibody survival benefit in metastatic colorectal cancer: a meta-analysis of randomized, controlled trials. Ann Oncol2015;26:13–21.
HelblingDBornerM. Successful challenge with the fully human EGFR antibody panitumumab following an infusion reaction with the chimeric EGFR antibody cetuximab. Ann Oncol2007;18:963–964.
HeunJHolenK. Treatment with panitumumab after a severe infusion reaction to cetuximab in a patient with metastatic colorectal cancer: a case report. Clin Colorectal Cancer2007;6:529–531.
ReschGSchaberl-MoserRKierP. Infusion reactions to the chimeric EGFR inhibitor cetuximab—change to the fully human anti-EGFR monoclonal antibody panitumumab is safe. Ann Oncol2011;22:486–487.
JonkerDJO'CallaghanCJKarapetisCS. Cetuximab for the treatment of colorectal cancer. N Engl J Med2007;357:2040–2048.
LievreABachetJBBoigeV. KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol2008;26:374–379.
PetrelliFBorgonovoKBarniS. The predictive role of skin rash with cetuximab and panitumumab in colorectal cancer patients: a systematic review and meta-analysis of published trials. Target Oncol2013;8:173–181.
StintzingSKapaunCLaubenderRP. Prognostic value of cetuximab-related skin toxicity in metastatic colorectal cancer patients and its correlation with parameters of the epidermal growth factor receptor signal transduction pathway: results from a randomized trial of the GERMAN AIO CRC Study Group. Int J Cancer2013;132:236–245.
Van CutsemETejparSVanbeckevoortD. Intrapatient cetuximab dose escalation in metastatic colorectal cancer according to the grade of early skin reactions: the randomized EVEREST study. J Clin Oncol2012;30:2861–2868.
BurtnessBAnadkatMBastiS. NCCN Task Force Report: management of dermatologic and other toxicities associated with EGFR inhibition in patients with cancer. J Natl Compr Canc Netw2009;7(Suppl 1):S5–21; quiz S22–24.
PetrelliFCabidduMBorgonovoKBarniS. Risk of venous and arterial thromboembolic events associated with anti-EGFR agents: a meta-analysis of randomized clinical trials. Ann Oncol2012;23:1672–1679.
ZhangDYeJXuTXiongB. Treatment related severe and fatal adverse events with cetuximab in colorectal cancer patients: a meta-analysis. J Chemother2013;25:170–175.
HechtJRMitchellEChidiacT. A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer. J Clin Oncol2009;27:672–680.
BruleSYJonkerDJKarapetisCS. Location of colon cancer (right-sided versus left-sided) as a prognostic factor and a predictor of benefit from cetuximab in NCIC CO.17. Eur J Cancer2015;51:1405–1414.
MorettoRCremoliniCRossiniD. Location of primary tumor and benefit from anti-epidermal growth factor receptor monoclonal antibodies in patients with RAS and BRAF wild-type metastatic colorectal cancer. Oncologist2016;21:988–994.
LoupakisFYangDYauL. Primary tumor location as a prognostic factor in metastatic colorectal cancer. J Natl Cancer Inst2015;107:doi: 10.1093/jnci/dju427.
LeeMSAdvaniSMMorrisJ. Association of primary (1°) site and molecular features with progression-free survival (PFS) and overall survival (OS) of metastatic colorectal cancer (mCRC) after anti-epidermal growth factor receptor (αEGFR) therapy [abstract]. J Clin Oncol2016;34(Suppl):Abstract 3506.
ChenKHShaoYYChenHM. Primary tumor site is a useful predictor of cetuximab efficacy in the third-line or salvage treatment of KRAS wild-type (exon 2 non-mutant) metastatic colorectal cancer: a nationwide cohort study. BMC Cancer2016;16:327.
WarschkowRSulzMCMartiL. Better survival in right-sided versus left-sided stage I - III colon cancer patients. BMC Cancer2016;16:554.
SchragDWengSBrooksG. The relationship between primary tumor sidedness and prognosis in colorectal cancer [abstract]. J Clin Oncol2016;34(Suppl):Abstract 3505.
VenookAPNiedzwieckiDInnocentiF. Impact of primary (1°) tumor location on overall survival (OS) and progression-free survival (PFS) in patients (pts) with metastatic colorectal cancer (mCRC): analysis of CALGB/SWOG 80405 (Alliance) [abstract]. J Clin Oncol2016;34(Suppl):Abstract 3504.
VenookAPNiedzwieckiDInnocentiF. Impact of primary (1°) tumor location on Overall Survival (OS) and Progression Free Survival (PFS) in patients (pts) with metastatic colorectal cancer (mCRC): analysis of All RAS wt patients on CALGB / SWOG 80405 (Alliance) [abstract]. Presented at ESMO Congress 2016; October7–112016; Copenhagen, Denmark.
AntonacopoulouAGTsamandasACPetsasT. EGFR, HER-2 and COX-2 levels in colorectal cancer. Histopathology2008;53:698–706.
McKayJAMurrayLJCurranS. Evaluation of the epidermal growth factor receptor (EGFR) in colorectal tumours and lymph node metastases. Eur J Cancer2002;38:2258–2264.
SpanoJPLagorceCAtlanD. Impact of EGFR expression on colorectal cancer patient prognosis and survival. Ann Oncol2005;16:102–108.
YenLCUenYHWuDC. Activating KRAS mutations and overexpression of epidermal growth factor receptor as independent predictors in metastatic colorectal cancer patients treated with cetuximab. Ann Surg2010;251:254–260.
HechtJRMitchellENeubauerMA. Lack of correlation between epidermal growth factor receptor status and response to Panitumumab monotherapy in metastatic colorectal cancer. Clin Cancer Res2010;16:2205–2213.
SaltzLBMeropolNJLoehrerPJ. Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol2004;22:1201–1208.
BaselgaJRosenN. Determinants of RASistance to anti-epidermal growth factor receptor agents. J Clin Oncol2008;26:1582–1584.
BokemeyerCBondarenkoIMakhsonA. Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol2009;27:663–671.
De RoockWPiessevauxHDe SchutterJ. KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab. Ann Oncol2008;19:508–515.
KarapetisCSKhambata-FordSJonkerDJ. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med2008;359:1757–1765.
Khambata-FordSGarrettCRMeropolNJ. Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab. J Clin Oncol2007;25:3230–3237.
TejparSCelikISchlichtingM. Association of KRAS G13D tumor mutations with outcome in patients with metastatic colorectal cancer treated with first-line chemotherapy with or without cetuximab. J Clin Oncol2012;30:3570–3577.
DouillardJYOlinerKSSienaS. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med2013;369:1023–1034.
AllegraCJRumbleRBHamiltonSR. Extended RAS gene mutation testing in metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy: American Society of Clinical Oncology provisional clinical opinion update 2015. J Clin Oncol2016;34:179–185.
ArtaleSSartore-BianchiAVeroneseSM. Mutations of KRAS and BRAF in primary and matched metastatic sites of colorectal cancer. J Clin Oncol2008;26:4217–4219.
Etienne-GrimaldiMCFormentoJLFrancoualM. K-Ras mutations and treatment outcome in colorectal cancer patients receiving exclusive fluoropyrimidine therapy. Clin Cancer Res2008;14:4830–4835.
KnijnNMekenkampLJKlompM. KRAS mutation analysis: a comparison between primary tumours and matched liver metastases in 305 colorectal cancer patients. Br J Cancer2011;104:1020–1026.
WangHLLopateguiJAminMBPattersonSD. KRAS mutation testing in human cancers: the pathologist's role in the era of personalized medicine. Adv Anat Pathol2010;17:23–32.
MonzonFAOginoSHammondMEH. The role of KRAS mutation testing in the management of patients with metastatic colorectal cancer. Arch Pathol Lab Med2009;133:1600–1606.
RothADTejparSDelorenziM. Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC-3, EORTC 40993, SAKK 60-00 trial. J Clin Oncol2010;28:466–474.
DahabrehIJTerasawaTCastaldiPJTrikalinosTA. Systematic review: anti-epidermal growth factor receptor treatment effect modification by KRAS mutations in advanced colorectal cancer. Ann Intern Med2011;154:37–49.
YoonHHTougeronDShiQ. KRAS codon 12 and 13 mutations in relation to disease-free survival in BRAF-wild-type stage III colon cancers from an adjuvant chemotherapy trial (N0147 alliance). Clin Cancer Res2014;20:3033–3043.
De RoockWJonkerDJDi NicolantonioF. Association of KRAS p.G13D mutation with outcome in patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab. JAMA2010;304:1812–1820.
PeetersMDouillardJYVan CutsemE. Mutant KRAS codon 12 and 13 alleles in patients with metastatic colorectal cancer: assessment as prognostic and predictive biomarkers of response to panitumumab. J Clin Oncol2013;31:759–765.
SchirripaMLoupakisFLonardiS. Phase II study of single-agent cetuximab in KRAS G13D mutant metastatic colorectal cancer. Ann Oncol2015;26:2503.
SegelovEThavaneswaranSWaringPM. Response to cetuximab with or without irinotecan in patients with refractory metastatic colorectal cancer harboring the KRAS G13D mutation: Australasian Gastro-Intestinal Trials Group ICECREAM study. J Clin Oncol2016;34:2258–2264.
PriceTJBruhnMALeeCK. Correlation of extended RAS and PIK3CA gene mutation status with outcomes from the phase III AGITG MAX study involving capecitabine alone or in combination with bevacizumab plus or minus mitomycin C in advanced colorectal cancer. Br J Cancer2015;112:963–970.
HeinemannVvon WeikersthalLFDeckerT. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol2014;15:1065–1075.
TolJNagtegaalIDPuntCJ. BRAF mutation in metastatic colorectal cancer. N Engl J Med2009;361:98–99.
Van CutsemEKohneCHLangI. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol2011;29:2011–2019.
MaughanTSAdamsRASmithCG. Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet2011;377:2103–2114.
DaviesHBignellGRCoxC. Mutations of the BRAF gene in human cancer. Nature2002;417:949–954.
IkenoueTHikibaYKanaiF. Functional analysis of mutations within the kinase activation segment of B-Raf in human colorectal tumors. Cancer Res2003;63:8132–8137.
WanPTGarnettMJRoeSM. Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell2004;116:855–867.
BokemeyerCCutsemEVRougierP. 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 Cancer2012;48:1466–1475.
Di NicolantonioFMartiniMMolinariF. Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol2008;26:5705–5712.
Laurent-PuigPCayreAManceauG. Analysis of PTEN, BRAF, and EGFR status in determining benefit from cetuximab therapy in wild-type KRAS metastatic colon cancer. J Clin Oncol2009;27:5924–5930.
LoupakisFRuzzoACremoliniC. KRAS codon 61, 146 and BRAF mutations predict resistance to cetuximab plus irinotecan in KRAS codon 12 and 13 wild-type metastatic colorectal cancer. Br J Cancer2009;101:715–721.
De RoockWClaesBBernasconiD. Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol2010;11:753–762.
SeymourMTBrownSRMiddletonG. Panitumumab and irinotecan versus irinotecan alone for patients with KRAS wild-type, fluorouracil-resistant advanced colorectal cancer (PICCOLO): a prospectively stratified randomised trial. Lancet Oncol2013;14:749–759.
PietrantonioFPetrelliFCoinuA. Predictive role of BRAF mutations in patients with advanced colorectal cancer receiving cetuximab and panitumumab: a meta-analysis. Eur J Cancer2015;51:587–594.
RowlandADiasMMWieseMD. 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 Cancer2015;112:1888–1894.
ChenDHuangJFLiuK. BRAFV600E mutation and its association with clinicopathological features of colorectal cancer: a systematic review and meta-analysis. PLoS One2014;9:e90607.
PriceTJHardinghamJELeeCK. Impact of KRAS and BRAF gene mutation status on outcomes from the phase III AGITG MAX trial of capecitabine alone or in combination with bevacizumab and mitomycin in advanced colorectal cancer. J Clin Oncol2011;29:2675–2682.
Safaee ArdekaniGJafarnejadSMTanL. The prognostic value of BRAF mutation in colorectal cancer and melanoma: a systematic review and meta-analysis. PLoS One2012;7:e47054.
SamowitzWSSweeneyCHerrickJ. Poor survival associated with the BRAF V600E mutation in microsatellite-stable colon cancers. Cancer Res2005;65:6063–6069.
SaridakiZPapadatos-PastosDTzardiM. BRAF mutations, microsatellite instability status and cyclin D1 expression predict metastatic colorectal patients' outcome. Br J Cancer2010;102:1762–1768.
XuQXuATZhuMM. Predictive and prognostic roles of BRAF mutation in patients with metastatic colorectal cancer treated with anti-epidermal growth factor receptor monoclonal antibodies: a meta-analysis. J Dig Dis2013;14:409–416.
ClancyCBurkeJPKaladyMFCoffeyJC. BRAF mutation is associated with distinct clinicopathological characteristics in colorectal cancer: a systematic review and meta-analysis. Colorectal Dis2013;15:e711–718.
SantiniDSpotoCLoupakisF. High concordance of BRAF status between primary colorectal tumours and related metastatic sites: implications for clinical practice. Ann Oncol2010;21:1565.
Sartore-BianchiATrusolinoLMartinoC. Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-of-concept, multicentre, open-label, phase 2 trial. Lancet Oncol2016;17:738–746.
RaghavKPSOvermanMJYuR. HER2 amplification as a negative predictive biomarker for anti-epidermal growth factor receptor antibody therapy in metastatic colorectal cancer [abstract]. J Clin Oncol2016;34(Suppl):Abstract 3517.
ValtortaEMartinoCSartore-BianchiA. Assessment of a HER2 scoring system for colorectal cancer: results from a validation study. Mod Pathol2015;28:1481–1491.
HurwitzHHainsworthJDSwantonC. Targeted therapy for gastrointestinaI (GI) tumors based on molecular profiles: early results from MyPathway, an open-label phase IIa basket study in patients with advanced solid tumors [abstract]. J Clin Oncol2016;34(Suppl):Abstract 653.
WuSWMaCCLiWH. Does overexpression of HER-2 correlate with clinicopathological characteristics and prognosis in colorectal cancer? Evidence from a meta-analysis. Diagn Pathol2015;10:144.
MartinVLandiLMolinariF. HER2 gene copy number status may influence clinical efficacy to anti-EGFR monoclonal antibodies in metastatic colorectal cancer patients. Br J Cancer2013;108:668–675.
LangIKohneCHFolprechtG. Quality of life analysis in patients with KRAS wild-type metastatic colorectal cancer treated first-line with cetuximab plus irinotecan, fluorouracil and leucovorin. Eur J Cancer2013;49:439–448.
Van CutsemELenzHJKohneCH. Fluorouracil, leucovorin, and irinotecan plus cetuximab treatment and RAS mutations in colorectal cancer. J Clin Oncol2015;33:692–700.
MitchellEPPiperdiBLacoutureME. The efficacy and safety of panitumumab administered concomitantly with FOLFIRI or Irinotecan in second-line therapy for metastatic colorectal cancer: the secondary analysis from STEPP (Skin Toxicity Evaluation Protocol With Panitumumab) by KRAS status. Clin Colorectal Cancer2011;10:333–339.
PeetersMPriceTJCervantesA. Final results from a randomized phase 3 study of FOLFIRI {+/–} panitumumab for second-line treatment of metastatic colorectal cancer. Ann Oncol2014;25:107–116.
BokemeyerCBondarenkoIHartmannJT. Efficacy according to biomarker status of cetuximab plus FOLFOX-4 as first-line treatment for metastatic colorectal cancer: the OPUS study. Ann Oncol2011;22:1535–1546.
TaiebJMaughanTBokemeyerC. Cetuximab combined with infusional 5-fluorouracil/folinic acid (5-FU/FA) and oxaliplatin in metastatic colorectal cancer (mCRC): a pooled analysis of COIN and OPUS study data [abstract]. J Clin Oncol2012;30(Suppl):Abstract 3574.
TveitKMGurenTGlimeliusB. Phase III trial of cetuximab with continuous or intermittent fluorouracil, leucovorin, and oxaliplatin (Nordic FLOX) versus FLOX alone in first-line treatment of metastatic colorectal cancer: the NORDIC-VII study. J Clin Oncol2012;30:1755–1762.
VenookAPNiedzwieckiDLenzHJ. CALGB/SWOG 80405: phase III trial of irinotecan/5-FU/leucovorin (FOLFIRI) or oxaliplatin/5-FU/leucovorin (mFOLFOX6) with bevacizumab (BV) or cetuximab (CET) for patients (pts) with KRAS wild-type (wt) untreated metastatic adenocarcinoma of the colon or rectum (MCRC) [abstract]. J Clin Oncol2014;32(Suppl):Abstract LBA3.
PrimroseJFalkSFinch-JonesM. Systemic chemotherapy with or without cetuximab in patients with resectable colorectal liver metastasis: the New EPOC randomised controlled trial. Lancet Oncol2014;15:601–611.
ModestDPStintzingSvon WeikersthalLF. Impact of subsequent therapies on outcome of the FIRE-3/AIO KRK0306 trial: first-line therapy with FOLFIRI plus cetuximab or bevacizumab in patients with KRAS wild-type tumors in metastatic colorectal cancer. J Clin Oncol2015;33:3718–3726.
O'NeilBHVenookAP. Trying to understand differing results of FIRE-3 and 80405: does the first treatment matter more than others?J Clin Oncol2015;33:3686–3688.
SchwartzbergLSRiveraFKarthausM. PEAK: a randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer. J Clin Oncol2014;32:2240–2247.
WolpinBMBassAJ. Managing advanced colorectal cancer: have we reached the PEAK with current therapies?J Clin Oncol2014;32:2200–2202.
Riesco-MartinezMCBerrySRKoYJ. Cost-effectiveness analysis of different sequences of the use of epidermal growth factor receptor inhibitors for wild-type KRAS unresectable metastatic colorectal cancer. J Oncol Pract2016;12:e710–723.
SchragDDueckACNaughtonMJ. Cost of chemotherapy for metastatic colorectal cancer with either bevacizumab or cetuximab: economic analysis of CALGB/SWOG 80405 [abstract]. J Clin Oncol2015;33(Suppl):Abstract 6504.
HoffPMPazdurRLassereY. Phase II study of capecitabine in patients with fluorouracil-resistant metastatic colorectal carcinoma. J Clin Oncol2004;22:2078–2083.
RougierPVan CutsemEBajettaE. Randomised trial of irinotecan versus fluorouracil by continuous infusion after fluorouracil failure in patients with metastatic colorectal cancer. Lancet1998;352:1407–1412.
KimGPSargentDJMahoneyMR. Phase III noninferiority trial comparing irinotecan with oxaliplatin, fluorouracil, and leucovorin in patients with advanced colorectal carcinoma previously treated with fluorouracil: N9841. J Clin Oncol2009;27:2848–2854.
SegelovEChanDShapiroJ. The role of biological therapy in metastatic colorectal cancer after first-line treatment: a meta-analysis of randomised trials. Br J Cancer2014;111:1122–1131.
HofheinzRDRonellenfitschUKubickaS. Treatment with antiangiogenic drugs in multiple lines in patients with metastatic colorectal cancer: meta-analysis of randomized trials. Gastroenterol Res Pract2016;2016:9189483.
PeetersMOlinerKPriceTJ. Analysis of KRAS/NRAS mutations in a phase 3 study of panitumumab with FOLFIRI compared with FOLFIRI alone as second-line treatment for metastatic colorectal cancer. Clin Cancer Res2015;21:5469–5479.
SobreroAFMaurelJFehrenbacherL. EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J Clin Oncol2008;26:2311–2319.
PriceTJPeetersMKimTW. Panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (ASPECCT): a randomised, multicentre, open-label, non-inferiority phase 3 study. Lancet Oncol2014;15:569–579.
BennounaJSastreJArnoldD. Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol2013;14:29–37.
KubickaSGreilRAndreT. Bevacizumab plus chemotherapy continued beyond first progression in patients with metastatic colorectal cancer previously treated with bevacizumab plus chemotherapy: ML18147 study KRAS subgroup findings. Ann Oncol2013;24:2342–2349.
MasiGSalvatoreLBoniL. Continuation or reintroduction of bevacizumab beyond progression to first-line therapy in metastatic colorectal cancer: final results of the randomized BEBYP trial. Ann Oncol2015;26:724–730.
IwamotoSTakahashiTTamagawaH. FOLFIRI plus bevacizumab as second-line therapy in patients with metastatic colorectal cancer after first-line bevacizumab plus oxaliplatin-based therapy: the randomized phase III EAGLE study. Ann Oncol2015;26:1427–1433.
CartwrightTHYimYMYuE. Survival outcomes of bevacizumab beyond progression in metastatic colorectal cancer patients treated in US community oncology. Clin Colorectal Cancer2012;11:238–246.
GrotheyAFlickEDCohnAL. Bevacizumab exposure beyond first disease progression in patients with metastatic colorectal cancer: analyses of the ARIES observational cohort study. Pharmacoepidemiol Drug Saf2014;23:726–734.
GoldsteinDAEl-RayesBF. Considering efficacy and cost, where does ramucirumab fit in the management of metastatic colorectal cancer?Oncologist2015;20:981–982.
ZALTRAP [package insert]. Bridgewater, NJ: Regeneron Pharmaceuticals, Inc./sanofi-aventis U.S. LLC; 2016.
TaberneroJVan CutsemELakomyR. Aflibercept versus placebo in combination with fluorouracil, leucovorin and irinotecan in the treatment of previously treated metastatic colorectal cancer: prespecified subgroup analyses from the VELOUR trial. Eur J Cancer2014;50:320–331.
FolprechtGPericayCSaundersMP. Oxaliplatin and 5-FU/folinic acid (modified FOLFOX6) with or without aflibercept in first-line treatment of patients with metastatic colorectal cancer: the AFFIRM study. Ann Oncol2016;27:1273–1279.
CYRAMZA [package insert]. Indianapolis, IN: Eli Lilly and Company; 2015.
TaberneroJYoshinoTCohnAL. Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomised, double-blind, multicentre, phase 3 study. Lancet Oncol2015;16:499–508.
STIVARGA [package insert]. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2016.
LiJQinSXuR. Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol2015;16:619–629.
BelumVRWuSLacoutureME. Risk of hand-foot skin reaction with the novel multikinase inhibitor regorafenib: a meta-analysis. Invest New Drugs2013;31:1078–1086.
CutsemEVCiardielloFSeitzJF. Results from the large, open-label phase 3b CONSIGN study of regorafenib in patients with previously treated metastatic colorectal cancer [abstract]. Ann Oncol2015;26(Suppl 4):Abstract LBA-05.
AdenisAde la FouchardiereCPauleB. Survival, safety, and prognostic factors for outcome with Regorafenib in patients with metastatic colorectal cancer refractory to standard therapies: results from a multicenter study (REBACCA) nested within a compassionate use program. BMC Cancer2016;16:412.
BendellJCRosenLSMayerRJ. Phase 1 study of oral TAS-102 in patients with refractory metastatic colorectal cancer. Cancer Chemother Pharmacol2015;76:925–932.
YoshinoTMizunumaNYamazakiK. TAS-102 monotherapy for pretreated metastatic colorectal cancer: a double-blind, randomised, placebo-controlled phase 2 trial. Lancet Oncol2012;13:993–1001.
LONSURF [package insert]. Tokyo, Japan: Taiho Pharmaceutical Co., Ltd.; 2015.
YoshinoTUetakeHFujitaN. TAS-102 safety in metastatic colorectal cancer: results from the first postmarketing surveillance study. Clin Colorectal Cancer2016;15:e205–211.
KoopmanMKortmanGAMMekenkampL. Deficient mismatch repair system in patients with sporadic advanced colorectal cancer. Br J Cancer2009;100:266–273.
LochheadPKuchibaAImamuraY. Microsatellite instability and BRAF mutation testing in colorectal cancer prognostication. J Natl Cancer Inst2013;105:1151–1156.
VenderboschSNagtegaalIDMaughanTS. Mismatch repair status and BRAF mutation status in metastatic colorectal cancer patients: a pooled analysis of the CAIRO, CAIRO2, COIN, and FOCUS studies. Clin Cancer Res2014;20:5322–5330.
TopalianSLHodiFSBrahmerJR. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med2012;366:2443–2454.
KEYTRUDA [package insert]. Whitehouse Station, NJ: Merck & Co, Inc.; 2016.
LeDTUramJNWangH. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med2015;372:2509–2520.
OPDIVO [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2015.
OvermanMJKopetzSMcDermottRS. Nivolumab {+/–} ipilimumab in treatment (tx) of patients (pts) with metastatic colorectal cancer (mCRC) with and without high microsatellite instability (MSI-H): CheckMate-142 interim results [abstract]. J Clin Oncol2016;34(Suppl):Abstract 3501.
SulJBlumenthalGMJiangX. FDA approval summary: pembrolizumab for the treatment of patients with metastatic non-small cell lung cancer whose tumors express programmed death-ligand 1. Oncologist2016;21:643–650.
LewisC. Programmed death-1 inhibition in cancer with a focus on non-small cell lung cancer: rationale, nursing implications, and patient management strategies. Clin J Oncol Nurs2016;20:319–326.
HofmannLForschnerALoquaiC. Cutaneous, gastrointestinal, hepatic, endocrine, and renal side-effects of anti-PD-1 therapy. Eur J Cancer2016;60:190–209.
ZimmerLGoldingerSMHofmannL. Neurological, respiratory, musculoskeletal, cardiac and ocular side-effects of anti-PD-1 therapy. Eur J Cancer2016;60:210–225.
NaidooJWangXWooKM. Pneumonitis in patients treated with anti-programmed death-1/programmed death ligand 1 therapy[published online ahead of print September 19 2016]. J Clin Oncolpii: JCO682005.
NishinoMChambersESChongCR. Anti-PD-1 inhibitor-related pneumonitis in non-small cell lung cancer. Cancer Immunol Res2016;4:289–293.
NishinoMShollLMHodiFS. Anti-PD-1-related pneumonitis during cancer immunotherapy. N Engl J Med2015;373:288–290.
HechtJRCohnADakhilS. SPIRITT: a randomized, multicenter, phase II study of panitumumab with FOLFIRI and bevacizumab with FOLFIRI as second-line rreatment in patients with unresectable wild type KRAS metastatic colorectal cancer. Clin Colorectal Cancer2015;14:72–80.
All Time | Past Year | Past 30 Days | |
---|---|---|---|
Abstract Views | 1 | 1 | 0 |
Full Text Views | 2449 | 2449 | 266 |
PDF Downloads | 640 | 640 | 64 |
EPUB Downloads | 0 | 0 | 0 |