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01-03-2017 | Review Article

Targeted Therapies in Elderly Patients with Metastatic Colorectal Cancer: A Review of the Evidence

Authors: Gonzalo Tapia Rico, Amanda R. Townsend, Vy Broadbridge, Timothy J. Price

Published in: Drugs & Aging | Issue 3/2017

Abstract

Metastatic colorectal cancer (mCRC) is the third leading cause of cancer deaths worldwide. As the population of the western world ages, the incidence of colorectal tumours among elderly patients is increasing and consequently so is the demand for treatments for elderly patients. Unfortunately, elderly patients (≥65 years) often go untreated and they are also under-represented in clinical trials. Yet there is some evidence suggesting that ‘fit’ elderly patients have similar outcomes and tolerance to chemotherapy treatment to their younger counterparts (although the definition of fitness in the elderly population is still a matter of debate). The evidence supporting the administration of new targeted therapies in patients older than 65 years is scarce and more research is needed. In this paper, we review all the available data concerning the use of targeted therapies for mCRC in patients older than 65 years of age and discuss the differences between this age subgroup and younger patients.

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J. 2016;66(1):7–30.CrossRef

Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer. 2013;49(6):1374–403.CrossRefPubMed

Guyot F, Faivre J, Manfredi S, Meny B, Bonithon-Kopp C, Bouvier AM. Time trends in the treatment and survival of recurrences from colorectal cancer. Ann Oncol. 2005;16(5):756–61.CrossRefPubMed

Siegel RL, Ward EM, Jemal A. Trends in colorectal cancer incidence rates in the United States by tumor location and stage, 1992–2008. Cancer Epidemiol Biomarkers Prev. 2012;21(3):411–6.CrossRefPubMed

Hurria A, Togawa K, Mohile SG, Owusu C, Klepin HD, Gross CP, et al. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol. 2011;29(25):3457–65.CrossRefPubMedPubMedCentral

Aapro MS, Kohne CH, Cohen HJ, Extermann M. Never too old? Age should not be a barrier to enrollment in cancer clinical trials. Oncologist. 2005;10(3):198–204.CrossRefPubMed

Lewis JH, Kilgore ML, Goldman DP, Trimble EL, Kaplan R, Montello MJ, et al. Participation of patients 65 years of age or older in cancer clinical trials. J Clin Oncol. 2003;21(7):1383–9.CrossRefPubMed

Popescu RA, Norman A, Ross PJ, Parikh B, Cunningham D. Adjuvant or palliative chemotherapy for colorectal cancer in patients 70 years or older. J Clin Oncol. 1999;17(8):2412–8.PubMed

Goldberg RM, Tabah-Fisch I, Bleiberg H, de Gramont A, Tournigand C, Andre T, et al. Pooled analysis of safety and efficacy of oxaliplatin plus fluorouracil/leucovorin administered bimonthly in elderly patients with colorectal cancer. J Clin Oncol. 2006;24(25):4085–91.CrossRefPubMed

10.

Schrag D, Cramer LD, Bach PB, Begg CB. Age and adjuvant chemotherapy use after surgery for stage III colon cancer. J Natl Cancer Inst. 2001;93(11):850–7.CrossRefPubMed

11.

Folprecht G, Seymour MT, Saltz L, Douillard JY, Hecker H, Stephens RJ, et al. Irinotecan/fluorouracil combination in first-line therapy of older and younger patients with metastatic colorectal cancer: combined analysis of 2,691 patients in randomized controlled trials. J Clin Oncol. 2008;26(9):1443–51.CrossRefPubMed

12.

O’Connell JB, Maggard MA, Liu JH, Etzioni DA, Ko CY. Are survival rates different for young and older patients with rectal cancer? Dis Colon Rectum. 2004;47(12):2064–9.CrossRefPubMed

13.

Caillet P, Canoui-Poitrine F, Vouriot J, Berle M, Reinald N, Krypciak S, et al. Comprehensive geriatric assessment in the decision-making process in elderly patients with cancer: ELCAPA study. J Clin Oncol. 2011;29(27):3636–42.CrossRefPubMed

14.

Kirstein MM, Lange A, Prenzler A, Manns MP, Kubicka S, Vogel A. Targeted therapies in metastatic colorectal cancer: a systematic review and assessment of currently available data. Oncologist. 2014;19(11):1156–68.CrossRefPubMedPubMedCentral

15.

Cunningham D, Lang I, Marcuello E, Lorusso V, Ocvirk J, Shin DB, AVEX Study Investigators, et al. Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial. Lancet Oncol. 2013;14(11):1077–85.CrossRefPubMed

16.

Aparicio T, Bouche O, Francois E, Maillard E, Kirscher S, Taïeb J, et al. PRODIGE 20: bevacizumab + chemotherapy (BEV-CT) versus chemotherapy alone (CT) in elderly patients (pts) with untreated metastatic colorectal cancer (mCRC)—a randomized phase II trial [abstract no. 3541]. J Clin Oncol. 2015;33 suppl.

17.

Wedding U, Honecker F, Bokemeyer C, Pientka L, Hoffken K. Tolerance to chemotherapy in elderly patients with cancer. Cancer Control. 2007;14(1):44–56.PubMed

18.

Zhao C, Li S, Liu Q. Meta-analysis of molecular targetted agents in the treatment of elderly patients with metastatic colorectal cancer: does the age matter? J Chemother. 2016;28(4):321–7.CrossRefPubMed

19.

Hurwitz HI, Yi J, Ince W, Novotny WF, Rosen O. The clinical benefit of bevacizumab in metastatic colorectal cancer is independent of K-ras mutation status: analysis of a phase III study of bevacizumab with chemotherapy in previously untreated metastatic colorectal cancer. Oncologist. 2009;14(1):22–8.CrossRefPubMed

20.

Kabbinavar FF, Schulz J, McCleod M, Patel T, Hamm JT, Hecht JR, et al. Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: results of a randomized phase II trial. J Clin Oncol. 2005;23(16):3697–705.CrossRefPubMed

21.

Giantonio BJ, Catalano PJ, Meropol NJ, O’Dwyer PJ, Mitchell EP, Alberts SR, et al. 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 Oncol. 2007;25(12):1539–44.CrossRefPubMed

22.

Cassidy J, Clarke S, Diaz-Rubio E, Scheithauer W, Figer A, Wong R, et al. XELOX vs FOLFOX-4 as first-line therapy for metastatic colorectal cancer: NO16966 updated results. Br J Cancer. 2011;105(1):58–64.CrossRefPubMedPubMedCentral

23.

Price TJ, Zannino D, Wilson K, Simes RJ, Cassidy J, Van Hazel GA, et al. Bevacizumab is equally effective and no more toxic in elderly patients with advanced colorectal cancer: a subgroup analysis from the AGITG MAX trial: an international randomised controlled trial of capecitabine, bevacizumab and mitomycin C. Ann Oncol. 2012;23(6):1531–6.CrossRefPubMed

24.

Bennouna J, Sastre J, Arnold D, Osterlund P, Greil R, Van Cutsem E, et al. ML18147 Study Investigators. Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol. 2013;14(1):29–37.CrossRefPubMed

25.

Fyfe GA, Hurwitz H, Fehrenbacher L, Cartwright T, Hainsworth J, Heim W, et al. Bevacizumab plus irinotecan/5-FU/leucovorin for treatment of metastatic colorectal cancer results in survival benefit in all pre-specified patient subgroups [poster]. J Clin Oncol (Meeting Abstracts). 2004;22(14_suppl):3617.

26.

Cassidy J, Saltz LB, Giantonio BJ, Kabbinavar FF, Hurwitz HI, Rohr UP. Effect of bevacizumab in older patients with metastatic colorectal cancer: pooled analysis of four randomized studies. J Cancer Res Clin Oncol. 2010;136(5):737–43.CrossRefPubMed

27.

Hurwitz HI, Tebbutt NC, Kabbinavar F, Giantonio BJ, Guan ZZ, Mitchell L, et al. Efficacy and safety of bevacizumab in metastatic colorectal cancer: pooled analysis from seven randomized controlled trials. Oncologist. 2013;18(9):1004–12.CrossRefPubMedPubMedCentral

28.

Pinto C, Antonuzzo L, Porcu L, Aprile G, Maiello E, Masi G, et al. Efficacy and safety of bevacizumab combined with fluoropyrimidine monotherapy for unfit or older patients with metastatic colorectal cancer: a systematic review and meta-analysis. Clin Colorectal Cancer. 2016;. doi:10.1016/j.clcc.2016.08.006.PubMed

29.

Shankaran V, Mummy D, Koepl L, Blough D, Yim YM, Yu E, et al. Adverse events associated with bevacizumab and chemotherapy in older patients with metastatic colorectal cancer. Clin Colorectal Cancer. 2013;12(3):204-13.e1.CrossRef

30.

Slavicek L, Pavlik T, Tomasek J, Bortlicek Z, Buchler T, Melichar B, et al. Efficacy and safety of bevacizumab in elderly patients with metastatic colorectal cancer: results from the Czech population-based registry. BMC Gastroenterol. 2014;14:53.CrossRefPubMedPubMedCentral

31.

Hatake K, Doaa T, Uetake H, Takahashi Y, Ishihara Y, Shirao K. Bevacizumab safety in Japanese patients with colorectal cancer. Jpn J Clin Oncol. 2016;46(3):234–40.CrossRefPubMed

32.

Tahover E, Hubert A, Temper M, Salah A, Peretz T, Hamburger T, et al. An observational cohort study of bevacizumab and chemotherapy in metastatic colorectal cancer patients: safety and efficacy with analysis by age group. Target Oncol. 2015;10(1):55–63.CrossRefPubMed

33.

Kozloff MF, Berlin J, Flynn PJ, Kabbinavar F, Ashby M, Dong W, et al. Clinical outcomes in elderly patients with metastatic colorectal cancer receiving bevacizumab and chemotherapy: results from the BRiTE observational cohort study. Oncology. 2010;78(5–6):329–39.CrossRefPubMed

34.

Van Cutsem E, Rivera F, Berry S, Kretzschmar A, Michael M, DiBartolomeo M, et al. Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal cancer: the BEAT study. Ann Oncol. 2009;20(11):1842–7.CrossRefPubMed

35.

Hofheinz R, Petersen V, Kindler M, Schulze M, Seraphin J, Hoeffkes HG, et al. Bevacizumab in first-line treatment of elderly patients with metastatic colorectal cancer: German community-based observational cohort study results. BMC Cancer. 2014;14:761.CrossRefPubMedPubMedCentral

36.

Rosati G, Avallone A, Aprile G, Butera A, Reggiardo G, Bilancia D. XELOX and bevacizumab followed by single-agent bevacizumab as maintenance therapy as first-line treatment in elderly patients with advanced colorectal cancer: the boxe study. Cancer Chemother Pharmacol. 2013;71(1):257–64.CrossRefPubMed

37.

Pereira AAL, De Mendonga Rego JF, Hoff PM, Deeke Sasse A, Pimenta Riechelmann R. The effect of chemotherapy delivered until progression versus complete stop on the overall survival of patients with metastatic colorectal cancer: a meta-analysis of randomized trials [abstract no. 3542]. J Clin Oncol 2014;32(5 suppl).

38.

Hershman DL, Wright JD, Lim E, Buono DL, Tsai WY, Neugut AI. Contraindicated use of bevacizumab and toxicity in elderly patients with cancer. J Clin Oncol. 2013;31(28):3592–9.CrossRefPubMedPubMedCentral

39.

Bokemeyer C, Bondarenko I, Makhson A, Hartmann JT, Aparicio J, Zampino M, et al. Cetuximab plus 5-FU/FA/oxaliplatin (FOLFOX-4) versus FOLFOX-4 in the first-line treatment of metastatic colorectal cancer (mCRC): OPUS, a randomized phase II study [abstract]. J Clin Oncol. 2007;25(18 suppl):4035.

40.

Cutsem EV, Nowacki M, Lang I, Cascinu S, Shchepotin I, Maurel J, et al. Randomized phase III study of irinotecan and 5-FU/FA with or without cetuximab in the first-line treatment of patients with metastatic colorectal cancer (mCRC): the CRYSTAL trial [abstract]. J Clin Oncol. 2007;25(18 suppl):4000.

41.

Sobrero AF, Maurel J, Fehrenbacher L, Scheithauer W, Abubakr YA, Lutz MP, et al. EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J Clin Oncol. 2008;26(14):2311–9.CrossRefPubMed

42.

Venook AP, Niedzwiecki D, Innocenti F, Fruth B, Greene C, O’Neil BH, et al. Impact of primary (1º) 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 no. 3504]. J Clin Oncol 2016; 34 suppl.

43.

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: retrospective analyses of the CRYSTAL and FIRE-3 trials. JAMA Oncol. 2016;. doi:10.1001/jamaoncol.2016.3797.

44.

Folprecht G, Kohne C-H, Bokemeyer C, Rougier P, Schlichting M, Heeger S, et al. Cetuximab and 1st-line chemotherapy in elderly and younger patients with metastatic colorectal cancer (MCRC): a pooled analysis of the CRYSTAL and OPUS studies [abstract no 597P]. 35th ESMO Congress; 8–12 Oct 2010; Milan.

45.

Sastre J, Gravalos C, Rivera F, Massuti B, Valladares-Ayerbes M, Marcuello E, et al. First-line cetuximab plus capecitabine in elderly patients with advanced colorectal cancer: clinical outcome and subgroup analysis according to KRAS status from a Spanish TTD Group Study. Oncologist. 2012;17(3):339–45.CrossRefPubMedPubMedCentral

46.

Australasian Gastro-Intestinal Trials Group (AGITG). http://agitg.org.au/agitg-innovation-fund-awarded-for-colorectal-cancer-research/.

47.

Kienle D, Winterhalder R, Koeberle D, Horber D, Kueng M, Saletti P, et al. Cetuximab monotherapy and cetuximab plus capecitabine as first-line treatment in elderly patients with RAS- and BRAF wild-type metastatic colorectal cancer. Results of the multicenter phase II trial SAKK 41/10 [abstract no. 1322]. Eur J Cancer. 2015;51(Suppl. 3):S194–5.CrossRef

48.

Sahm S, Goehler T, Hering-Schubert C, Janssen J, Neumann UP, Schwittay M, et al. Outcome of patients with KRAS exon 2 wildtype (KRAS-wt) metastatic colorectal carcinoma (mCRC) with cetuximab-based first-line treatment in the non-interventional study ERBITAG and impact of comorbidity and age. ASCO Gastrointestinal Cancers Symposium, San Francisco, USA January 2016 [abstract no. 651]. J Clin Oncol 2016;34(suppl).

49.

Fornaro L, Baldi GG, Masi G, Allegrini G, Loupakis F, Vasile E, et al. Cetuximab plus irinotecan after irinotecan failure in elderly metastatic colorectal cancer patients: clinical outcome according to KRAS and BRAF mutational status. Crit Rev Oncol Hematol. 2011;78(3):243–51.CrossRefPubMed

50.

Bouchahda M, Macarulla T, Spano JP, Bachet JB, Lledo G, Andre T, et al. Cetuximab efficacy and safety in a retrospective cohort of elderly patients with heavily pretreated metastatic colorectal cancer. Crit Rev Oncol Hematol. 2008;67(3):255–62.CrossRefPubMed

51.

Jehn CF, Boning L, Kroning H, Possinger K, Luftner D. Cetuximab-based therapy in elderly comorbid patients with metastatic colorectal cancer. Br J Cancer. 2012;106(2):274–8.CrossRefPubMedPubMedCentral

52.

Pfeiffer P, Nielsen D, Bjerregaard J, Qvortrup C, Yilmaz M, Jensen B. Biweekly cetuximab and irinotecan as third-line therapy in patients with advanced colorectal cancer after failure to irinotecan, oxaliplatin and 5-fluorouracil. Ann Oncol. 2008;19(6):1141–5.CrossRefPubMed

53.

Sastre J, Aranda E, Gravalos C, Massuti B, Varella-Garcia M, Rivera F, et al. First-line single-agent cetuximab in elderly patients with metastatic colorectal cancer. A phase II clinical and molecular study of the Spanish group for digestive tumor therapy (TTD). Crit Rev Oncol Hematol. 2011;77(1):78–84.CrossRefPubMed

54.

Uña Cidón E, Tamas H, Pilar A. Cetuximab as monotherapy in elderly patients with metastatic colorectal cancer [poster no. P-0247]. Ann Oncol. 2014;25(suppl 2):ii91.

55.

Asmis TR, Powell E, Karapetis CS, Jonker DJ, Tu D, Jeffery M, et al. Comorbidity, age and overall survival in cetuximab-treated patients with advanced colorectal cancer (ACRC)—results from NCIC CTG CO.17: a phase III trial of cetuximab versus best supportive care. Ann Oncol. 2011;22(1):118–26.CrossRefPubMed

56.

Van Cutsem E, Peeters M, Siena S, Humblet Y, Hendlisz A, Neyns B, et al. 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 Oncol. 2007;25(13):1658–64.CrossRefPubMed

57.

Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, et al. Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer. Ann Oncol. 2014;25(7):1346–55.CrossRefPubMed

58.

Schwartzberg LS, Rivera F, Karthaus M, Fasola G, Canon J-L, Hecht JR, et al. 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 Oncol. 2014;32(21):2240–7.CrossRefPubMed

59.

Peeters M, Price TJ, Cervantes A, Sobrero AF, Ducreux M, Hotko Y, et al. Final results from a randomized phase 3 study of FOLFIRI +/− panitumumab for second-line treatment of metastatic colorectal cancer. Ann Oncol. 2014;25(1):107–16.CrossRefPubMed

60.

Douillard J, Siena S, Peeters M, Koukakis R, Terwey J, Tabernero J. Impact of baseline age on efficacy and safety of first-line panitumumab (pmab) + FOLFOX4 vs FOLFOX4 treatment [abstract no. 547P]. Ann Oncol. 2014;25(suppl_4):iv187.CrossRef

61.

Sastre J, Massuti B, Pulido G, Guillen-Ponce C, Benavides M, Manzano JL, et al. First-line single-agent panitumumab in frail elderly patients with wild-type KRAS metastatic colorectal cancer and poor prognostic factors: a phase II study of the Spanish Cooperative Group for the Treatment of Digestive Tumours. Eur J Cancer. 2015;51(11):1371–80.CrossRefPubMed

62.

Pietrantonio F, Cremolini C, Aprile G, Lonardi S, Orlandi A, Mennitto A, et al. Single-agent panitumumab in frail elderly patients with advanced RAS and BRAF wild-type colorectal cancer: challenging drug label to light up new hope. Oncologist. 2015;20(11):1261–5.CrossRefPubMedPubMedCentral

63.

Van Cutsem E, Tabernero J, Lakomy R, Prenen H, Prausova J, Macarulla T, et al. 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 Oncol. 2012;30(28):3499–506.CrossRefPubMed

64.

Grothey A, Van Cutsem E, Sobrero A, Siena S, Falcone A, Ychou M, et al. CORRECT Study Group. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013;381(9863):303–12.CrossRefPubMed

65.

Demetri GD, Reichardt P, Kang YK, Blay JY, Rutkowski P, Gelderblom H, et al. GRID Study Investigators. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013;381(9863):295–302.CrossRefPubMed

66.

Carrato A, Benavides M, Massuti Sureda B, Federico Longo, Garcia Alfonso P, Falco E, et al. Regorafenib (REG) as a single agent for first-line treatment of frail and/or unfit for polychemotherapy (PChT) patients (pts) with metastatic colorectal cancer (mCRC): a phase II study of the Spanish Cooperative Group for Digestive Tumor Therapy (TTD) [abstract no. 3527]. 2016 ASCO Annual Meeting J Clin Oncol 2016;34 suppl.

67.

Van Cutsem E, Ciardiello F, Ychou M, Seitz JF, Hofheinz R, Arriaga YE, et al. Regorafenib in previously treated metastatic colorectal cancer (mCRC): Analysis of age subgroups in the open-label phase IIIb CONSIGN trial [abstract no. 3524]. J Clin Oncol 2016;34 suppl.

68.

Van Cutsem E, Ciardiello F, Seitz J-F, Hofheinz R, Verma U, Garcia-Carbonero R, et al. Results from the large, open-label phase 3b CONSIGN study of regorafenib in patients with previously treated metastatic colorectal cancer [abstract no. LBA-05]. Ann Oncol. 2015;26(suppl 4):iv118.CrossRef

69.

Tabernero J, Yoshino T, Cohn AL, Obermannova R, Bodoky G, Garcia-Carbonero R, et al. RAISE Study Investigators. 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 Oncol. 2015;16(5):499–508.CrossRefPubMed

70.

Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350(23):2335–42.CrossRefPubMed

71.

De Rosa M, Rega D, Costabile V, Duraturo F, Niglio A, Izzo P, et al. The biological complexity of colorectal cancer: insights into biomarkers for early detection and personalized care. Ther Adv Gastroenterol. 2016;9(6):861–86.CrossRef

72.

Sartore-Bianchi A, Trusolino L, Martino C, Bencardino K, Lonardi S, Bergamo F, et al. 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 Oncol. 2016;17(6):738–46.CrossRefPubMed

73.

Matos I, Elez E, Capdevila J, Tabernero J. Emerging tyrosine kinase inhibitors for the treatment of metastatic colorectal cancer. Expert Opin Emerg Drugs. 2016;21(3):267–82.CrossRefPubMed

74.

Gravalos C, Cassinello J, Fernandez-Ranada I, Holgado E. Role of tyrosine kinase inhibitors in the treatment of advanced colorectal cancer. Clin Colorectal Cancer. 2007;6(10):691–9.CrossRefPubMed

75.

Pal SK, Bergerot PG, Figlin RA. Tivozanib: current status and future directions in the treatment of solid tumors. Expert Opin Investig Drugs. 2012;21(12):1851–9.CrossRefPubMedPubMedCentral

76.

Kircher SM, Nimeiri HS, Benson AB 3rd. Targeting angiogenesis in colorectal cancer: tyrosine kinase inhibitors. Cancer J. 2016;22(3):182–9.CrossRefPubMed

77.

Boehm S, Rothermundt C, Hess D, Joerger M. Antiangiogenic drugs in oncology: a focus on drug safety and the elderly—a mini-review. Gerontology. 2010;56(3):303–9.CrossRefPubMed

78.

Kopetz S, Desai J, Chan E, Hecht JR, O’Dwyer PJ, Maru D, et al. Phase II pilot study of vemurafenib in patients with metastatic BRAF-mutated colorectal cancer. J Clin Oncol. 2015;33(34):4032–8.CrossRefPubMedPubMedCentral

79.

Corcoran RB, Atreya CE, Falchook GS, Kwak EL, Ryan DP, Bendell JC, et al. Combined BRAF and MEK inhibition with dabrafenib and trametinib in BRAF V600-mutant colorectal cancer. J Clin Oncol. 2015;33(34):4023–31.CrossRefPubMedPubMedCentral

80.

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.CrossRefPubMed

81.

Drake CG, Lipson EJ, Brahmer JR. Breathing new life into immunotherapy: review of melanoma, lung and kidney cancer. Nat Rev Clin Oncol. 2014;11(1):24–37.CrossRefPubMed

82.

Bupathi M, Wu C. Biomarkers for immune therapy in colorectal cancer: mismatch-repair deficiency and others. J Gastrointest Oncol. 2016;7(5):713–20.CrossRefPubMedPubMedCentral

83.

Lynch D, Murphy A. The emerging role of immunotherapy in colorectal cancer. Ann Transl Med. 2016;4(16):305.CrossRefPubMedPubMedCentral

84.

Koopman M, Kortman GA, Mekenkamp L, Ligtenberg MJ, Hoogerbrugge N, Antonini NF, et al. Deficient mismatch repair system in patients with sporadic advanced colorectal cancer. Br J Cancer. 2009;100(2):266–73.CrossRefPubMedPubMedCentral

Title: Targeted Therapies in Elderly Patients with Metastatic Colorectal Cancer: A Review of the Evidence
Authors: Gonzalo Tapia Rico
Amanda R. Townsend
Vy Broadbridge
Timothy J. Price
Publication date: 01-03-2017
Publisher: Springer International Publishing
Published in: Drugs & Aging / Issue 3/2017
Print ISSN: 1170-229X
Electronic ISSN: 1179-1969
DOI: https://doi.org/10.1007/s40266-017-0439-9

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