The changing face of treatment for metastatic colorectal cancer

References

• Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–86.
   PubMed Web of Science ®Google Scholar
• Meyerhardt JA, Mayer RJ. Systemic therapy for colorectal cancer. N Engl J Med. 2005;352:476–487.
   PubMed Web of Science ®Google Scholar
• Longley DB, Harkin DP, Johnston PG. 5-Fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer. 2003;3:330.
   PubMed Web of Science ®Google Scholar
• Sobrero AF, Aschele C, Bertino JR. Fluorouracil in colorectal cancer-a tale of two drugs: implications for biochemical modulation. J Clin Oncol. 1997;15:368–381.
   PubMed Web of Science ®Google Scholar
• Mocellin S, Baretta Z, Roqué I, et al. Second-line systemic therapy for metastatic colorectal cancer. Cochrane Database Syst Rev. 2017 Jan;27(1):CD006875.
   Google Scholar
• Schmoll HJ, Van Cutsem E, Stein A, et al. ESMO consensus guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making. Ann Oncol. 2012;23:2479–2516.
   PubMed Web of Science ®Google Scholar
• Van Cutsem E, Cervantes A, Adam R, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016;27:1386–1422.
   PubMed Web of Science ®Google Scholar
• Saltz LB, Cox JV, Blanke C, et al. Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. N Engl J Med. 2000;343:905–914.
   PubMed Web of Science ®Google Scholar
• Douillard JY, Cunningham D, Roth AD, et al. Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet. 2000;355:1041–1047.
   PubMed Web of Science ®Google Scholar
• Köhne CH, Van Cutsem E, Wils J, et al. Phase III study of weekly high-dose infusional fluorouracil plus folinic acid with or without irinotecan in patients with metastatic colorectal cancer: European organisation for research and treatment of cancer gastrointestinal group study 40986. J Clin Oncol. 2005;23:4856–4865.
   PubMed Web of Science ®Google Scholar
• de Gramont A, Figer A, Seymour M, et al. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol. 2000;18:2938–2947.
   PubMed Web of Science ®Google Scholar
• Giacchetti S, Perpoint B, Zidani R, et al. Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer. J Clin Oncol. 2000;18:136–147.
   PubMed Web of Science ®Google Scholar
• Goldberg RM, Sargent DJ, Morton RF, et al. A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol. 2004;22:23–30.
   PubMed Web of Science ®Google Scholar
• Glimelius B, Sorbye H, Balteskard L, et al. A randomized phase III multicenter trial comparing irinotecan in combination with the Nordic bolus 5-FU and folinic acid schedule or the bolus/infused de Gramont schedule (Lv5FU2) in patients with metastatic colorectal cancer. Ann Oncol. 2008;19:909–914.
   PubMed Web of Science ®Google Scholar
• Cassidy J, Clarke S, Diaz-Rubio E, et al. 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 Oncol. 2008;26:2006–2012.
   PubMed Web of Science ®Google Scholar
• Kelly ME, Spolverato G, Le GN, et al. Synchronous colorectal liver metastasis: a network meta-analysis review comparing classical, combined, and liver-first surgical strategies. J Surgical Oncol. 2015;111:341–351.
   PubMed Web of Science ®Google Scholar
• Hu C-Y, Bailey CE, You N, et al. Time trend analysis of primary tumor resection for stage IV colorectal cancer less surgery, improved survival. JAMA Surg. 2015;150:245–251.
   PubMed Web of Science ®Google Scholar
• van Rooijen KL, Shi Q, Goey KKH, et al. Prognostic value of primary tumour resection in synchronous metastatic colorectal cancer: individual patient data analysis of first-line randomised trials from the ARCAD database. Eur J Cancer. 2018;91:99–106.
   PubMed Web of Science ®Google Scholar
• Glynne-Jones R, Wyrwicz L, Tiret E, et al. Rectal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28(suppl_4):iv22–iv40.
   PubMed Web of Science ®Google Scholar
• Erlandsson J, Holm T, Pettersson D, et al. Optimal fractionation of preoperative radiotherapy and timing to surgery for rectal cancer (Stockholm III): a multicentre, randomised, non-blinded, phase 3, non-inferiority trial. Lancet Oncol. 2017;18:336–346.
   PubMed Web of Science ®Google Scholar
• Nilsson PJ, van Etten B, Hospers GAP, et al. Short-course radiotherapy followed by neo-adjuvant chemotherapy in locally advanced rectal cancer – the RAPIDO trial. BMC Cancer. 2013;13:279.
   PubMed Web of Science ®Google Scholar
• Holliday EB, Hunt A, You YN, et al. Short course radiation as a component of definitive multidisciplinary treatment for select patients with metastatic rectal adenocarcinoma. J Gastrointest Oncol. 2017;8:990–997.
   PubMed Web of Science ®Google Scholar
• Folprecht G, Grothey A, Alberts S, et al. Neoadjuvant treatment of unresectable colorectal liver metastases: correlation between tumour response and resection rates. Ann Oncol. 2005;16:1311–1319.
   PubMed Web of Science ®Google Scholar
• Okuno M, Hatano E, Nishino H, et al. Does response rate of chemotherapy with molecular target agents correlate with the conversion rate and survival in patients with unresectable colorectal liver metastases?: A systematic review. Ejso. 2017;43:1003–1012.
   PubMed Web of Science ®Google Scholar
• Van Cutsem E, Lenz HJ, Kohne CH, et al. Fluorouracil, leucovorin, and irinotecan plus cetuximab treatment and RAS mutations in colorectal cancer. J Clin Oncol. 2015;33:692–700.
   PubMed Web of Science ®Google Scholar
• Bokemeyer C, Kohne CH, Ciardiello F, et al. FOLFOX4 plus cetuximab treatment and RAS mutations in colorectal cancer. Eur J Cancer. 2015;51:1243–1252.
   PubMed Web of Science ®Google Scholar
• Douillard JY, Oliner KS, Siena S, et al. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med. 2013;369:1023–1034.
   PubMed Web of Science ®Google Scholar
• Saltz LB, Clarke S, Diaz-Rubio E, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol. 2008;26:2013–2019.
   PubMed Web of Science ®Google Scholar
• Stintzing S, Modest DP, Rossius L, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab for metastatic colorectal cancer (FIRE-3): a post-hoc analysis of tumour dynamics in the fi nal RAS wild-type subgroup of this randomised open-label phase 3 trial. Lancet Oncol. 2016;17:1426–1434.
   PubMed Web of Science ®Google Scholar
• Heinemann V, von Weikersthal LF, Decker T, et al. 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 Oncol. 2014;15:1065–1075.
   PubMed Web of Science ®Google Scholar
• Schwartzberg LS, Rivera F, Karthaus M, 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;32:2240–2247.
   PubMed Web of Science ®Google Scholar
• Venook AP, Niedzwiecki D, Lenz H-J, et al. Effect of first-line chemotherapy combined with cetuximab or bevacizumab on overall survival in patients with KRAS wild-type advanced or metastatic colorectal cancer a randomized clinical trial. JAMA. 2017;317:2392–2401.
   PubMed Web of Science ®Google Scholar
• Arnold D, Lueza B, Douillard J-Y, et al. Prognostic and predictive value of primary tumour side in patients with RAS wild-type metastatic colorectal cancer treated with chemotherapy and EGFR directed antibodies in six randomized trials. Ann Oncol. 2017;28:1713–1729.
   PubMed Web of Science ®Google Scholar
• Holch JW, Ricard I, Stintzing S, et al. The relevance of primary tumour location in patients with metastatic colorectal cancer: A meta-analysis of first-line clinical trials. Eur J Cancer. 2017;70:87–98.
   PubMed Web of Science ®Google Scholar
• Qin S, Xu J, Wang L, et al. First-line FOLFOX-4 ± cetuximab in patients with RAS wild-type (wt) metastatic colorectal cancer (mCRC): the open-label, randomized phase 3 TAILOR trial. Ann Oncol. 2016;27(Suppl 4):0–025.
   Google Scholar
• Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350:2335–2342.
   PubMed Web of Science ®Google Scholar
• Guan ZZ, Xu JM, Luo RC, et al. Efficacy and safety of bevacizumab plus chemotherapy in Chinese patients with metastatic colorectal cancer: a randomized phase III ARTIST trial. Chin J Cancer. 2011;30:682–689.
   PubMedGoogle Scholar
• Stathopoulos GP, Batziou C, Trafalis D, et al. Treatment of colorectal cancer with andwithout bevacizumab: a phase III study. Oncology. 2010;78:376–381.
   PubMed Web of Science ®Google Scholar
• Cunningham D, Lang I, Marcuello E, 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;14:1077–1085.
   PubMed Web of Science ®Google Scholar
• Tebbutt NC, Wilson K, Gebski VJ, et al. Capecitabine, bevacizumab, and mitomycin in first-line treatment of metastatic colorectal cancer: results of the Australasian gastrointestinal trials group randomized phase III MAX study. J Clin Oncol. 2010;28:3191–3198.
   PubMed Web of Science ®Google Scholar
• Passardi A, Nanni O, Tassinari D, et al. Effectiveness of bevacizumab added to standard chemotherapy in metastatic colorectal cancer: final results for first-line treatment from the ITACa randomized clinical trial. Ann Oncol. 2015;26:1201–1207.
   PubMed Web of Science ®Google Scholar
• Venook A, Niedzwiecki D, Innocenti F, et al. Impact of primary 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). J Clin Oncol. 2016;34(Suppl.;abstr 3504).
   Google Scholar
• Falcone A, Ricci S, Brunetti I, 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;25:1670–1676.
   PubMed Web of Science ®Google Scholar
• Cremolini C, Loupakis F, Antoniotti C, et al. Early tumor shrinkage and depth of response predict long-term outcome in metastatic colorectal cancer patients treated with first-line chemotherapy plus bevacizumab: results from phase III TRIBE trial by the Gruppo Oncologico del Nord Ovest. Ann Oncol. 2015;26:1188–1194.
   PubMed Web of Science ®Google Scholar
• Gruenberger T, Bridgewater J, Chau I, et al. Bevacizumab plus mFOLFOX-6 or FOLFOXIRI in patients with initially unresectable liver metastases from colorectal cancer: the OLIVIA multinational randomised phase II trial. Ann Oncol. 2015;26:702–708.
   PubMed Web of Science ®Google Scholar
• Bendell JC, Tan BR, Reeves JA, et al. Overall response rate in STEAM, a randomized, open-label, phase 2 trial of sequential and concurrent FOLFOXIRI-bevacizumab vs FOLFOX-bevacizumab for the first-line treatment of patients with metastatic colorectal cancer. J Clin Oncol. 2016;34(suppl 4S; abstr 492).
   Google Scholar
• Schmoll H-J, Meinert FM, Cygon F, et al. “CHARTA”: FOLFOX/bevacizumab vs FOLFOXIRI/bevacizumab in advanced colorectal cancer – final results, prognostic and potentially predictive factors from the randomized phase II trial of the AIO. ASCO. 2017. J Clin Oncol 35, 2017 (suppl; abstr 3533).
   Google Scholar
• Falcone A, Cremolini C, Loupakis F, et al. FOLFOXIRI plus bevacizumab (bev) followed by maintenance with bev alone or bev plus metronomic chemotherapy (metroCT) in metastatic colorectal cancer (mCRC): the phase II randomized MOMA trial. Ann Oncol. 2016;27(Supplement 6):LBA21.
   Google Scholar
• Geissler M, Martens UM, Knorrenschield R, et al. mFOLFOXIRI + Panitumumab versus FOLFOXIRI as first-line treatment in patients with RAS wild-type metastatic colorectal cancer m(CRC): a randomized phase II trial of the AIO (AIO-KRK-0109). Ann Oncol. 2017;28(Supplement 5):475O.
   Google Scholar
• Garufi C, Torsello A, Tumolo S, et al. Cetuximab plus chronomodulated irinotecan, 5-fluorouracil, leucovorin and oxaliplatin as neoadjuvant chemotherapy in colorectal liver metastases: POCHER trial. Br J Cancer. 2010;103:1542–1547.
   PubMed Web of Science ®Google Scholar
• Assenat E, Desseigne F, Thezenas S, et al. Cetuximab plus FOLFIRINOX (ERBIRINOX) as first-line treatment for unresectable metastatic colorectal cancer: a phase II trial. Oncologist. 2011;16:1557–1564.
   PubMed Web of Science ®Google Scholar
• Folprecht G1, Hamann S, Schütte K, et al. Dose escalating study of cetuximab and 5-FU/folinic acid (FA)/oxaliplatin/irinotecan (FOLFOXIRI) in first line therapy of patients with metastatic colorectal cancer. BMC Cancer. 2014;14:521.
   PubMed Web of Science ®Google Scholar
• Saridaki Z, Androulakis N, Vardakis N, et al. A triplet combination with irinotecan (CPT-11), oxaliplatin (LOHP), continuous infusion 5-fluorouracil and leucovorin (FOLFOXIRI) plus cetuximab as first-line treatment in KRAS wt, metastatic colorectal cancer: a pilot phase II trial. Br J Cancer. 2012;107:1932–1937.
   PubMed Web of Science ®Google Scholar
• Fornaro L1, Lonardi S, Masi G, et al. FOLFOXIRI in combination with panitumumab as first-line treatment in quadruple wild-type (KRAS, NRAS, HRAS, BRAF) metastatic colorectal cancer patients: a phase II trial by the Gruppo Oncologico Nord Ovest (GONO). Ann Oncol. 2013;24:2062–2067.
   PubMed Web of Science ®Google Scholar
• Cremolini C, Antoniotti C, Lonardi S, et al. Activity and safety of cetuximab plus modified FOLFOXIRI followed by maintenance with cetuximab or bevacizumab for RAS and BRAF wild-type metastatic colorectal cancer a randomized phase 2 clinical trial. JAMA Oncol. 2018;4:529–536.
   PubMed Web of Science ®Google Scholar
• Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372:2509–2520.
   PubMed Web of Science ®Google Scholar
• Rizvi NA, Hellmann MD, Snyder A, et al. Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer. Science. 2015;348:124–128.
   PubMed Web of Science ®Google Scholar
• Ay L, Lin E. Programmed death 1 blockade, an Achilles heel for MMR-deficient tumors? J Hematol Oncol. 2015;8:124.
   PubMed Web of Science ®Google Scholar
• Snyder A, Makarov V, Merghoub T, et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med. 2014;371:2189–2199.
   PubMed Web of Science ®Google Scholar
• Alex AK, Siqueira S, Coudry R, et al. Response to chemotherapy and prognosis in metastatic colorectal cancer with DNA deficient mismatch repair. Clin Colorectal Cancer. 2017;16:228–239.
   PubMed Web of Science ®Google Scholar
• Venderbosch S, Nagtegaal ID, Maughan TS, et al. 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 Res. 2014;20:5322–5330.
   PubMed Web of Science ®Google Scholar
• Le DT, Durham JN, Smith KN, et al. Mismatch-repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357:409–413.
   PubMed Web of Science ®Google Scholar
• Overman MJ, McDermott R, Leach JL, et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol. 2017;18:1182–1191.
   PubMed Web of Science ®Google Scholar
• Overman MJ, Lonardi S, Wong KYM, et al. Durable clinical benefit with nivolumab plus ipilimumab in DNA mismatch repair–deficient/microsatellite instability-high metastatic colorectal cancer. J Clin Oncol. 2018;36:773–779.
   PubMed Web of Science ®Google Scholar
• Tie J, Gibbs P, Lipton L, et al. targeted therapeutic development: analysis of a colorectal cancer patient population with the BRAF(V600E) mutation. Int J Cancer. 2011;128:2075–2084.
   PubMed Web of Science ®Google Scholar
• Sorbye H, Dragomir A, Sundström M, et al. High BRAF mutation frequency and marked survival differences in subgroups according to KRAS/BRAF mutation status and tumor tissue availability in a prospective population-based metastatic colorectal cancer cohort. PLoS ONE. 2015;10:e0131046.
   PubMed Web of Science ®Google Scholar
• Loupakis F, Cremolini C, Masi G, et al. Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer. N Engl J Med. 2014;371:1609–1618.
   PubMed Web of Science ®Google Scholar
• Pietrantonio F, Petrelli F, Coinu A, et al. Predictive role of BRAF mutations in patients with advanced colorectal cancer receiving cetuximab and panitumumab: A meta-analysis. Eur J Cancer. 2015;51:587–594.
   PubMed Web of Science ®Google Scholar
• Falchook GS, Long GV, Kurzrock R, et al. Dabrafenib in patients with melanoma, untreated brain metastases, and other solid tumours: A phase 1 dose-escalation trial. Lancet. 2012;379:1893–1901.
   PubMed Web of Science ®Google Scholar
• Kopetz S, Desai J, Chan E, et al. Phase II pilot study of vemurafenib in patients with metastatic BRAF-mutated colorectal cancer. J Clin Oncol. 2015;33:4032–4038.
   PubMed Web of Science ®Google Scholar
• Sorbye H, Pfeiffer P, Cavalli-Bjorkman N, et al. Clinical trial enrolment, patient characteristics, and survival differences in prospective registered metastatic colorectal cancer patients. Cancer. 2009;115:4679–4687.
   PubMed Web of Science ®Google Scholar
• Lemmens VE, de Haan N, Rutten HJ, et al. Improvements in population-based survival of patients presenting with metastatic rectal cancer in the south of the Netherlands, 1992–2008. Clin Exp Metastasis. 2011;28:283–290.
   PubMed Web of Science ®Google Scholar
• Sorbye H, Cvancarova M, Qvortrup C, et al. Age-dependent improvement in median and long-term survival in unselected population-based Nordic registries of patients with synchronous metastatic colorectal cancer. Ann Oncol. 2013;24:2354–2360.
   PubMed Web of Science ®Google Scholar
• Shayne M, Culakova E, Poniewierski MS, et al. Dose intensity and hematologic toxicity in older cancer patients receiving systemic chemotherapy. Cancer. 2007;110:1611–1620.
   PubMed Web of Science ®Google Scholar
• Sorbye H. Palliative chemotherapy in elderly patients with metastatic colorectal cancer: do we know how it should be used? Acta Oncol. 2012;51:819–821.
   PubMed Web of Science ®Google Scholar
• Sorbye H, Köhne CH, Sargent DJ, et al. Patient characteristics and stratification in medical treatment studies for metastatic colorectal cancer: a proposal for standardization of patient characteristic reporting and stratification. Ann Oncol. 2007;10:1666–1672.
   Web of Science ®Google Scholar
• Pfeiffer P, Qvortrup C, Bjerregaard JK. Current status of treatment of metastatic colorectal cancer with special reference to cetuximab and elderly patients. Onco Targets Ther. 2009;2:17–27.
   PubMed Web of Science ®Google Scholar
• Sargent DJ, Goldberg RM, Jacobson SD, et al. A pooled analysis of adjuvant chemotherapy for resected colon cancer in elderly patients. N Engl J Med. 2001;345:1091–1097.
   PubMed Web of Science ®Google Scholar
• Goldberg RM, Tabah-Fisch I, Bleiberg H, 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;24:4085–4091.
   PubMed Web of Science ®Google Scholar
• Folprecht G, Cunningham D, Ross P, et al. Efficacy of 5-fluorouracil-based chemotherapy in elderly patients with metastatic colorectal cancer: a pooled analysis of clinical trials. Ann Oncol. 2004;15:1330–1338.
   PubMed Web of Science ®Google Scholar
• Sanoff HK, Carpenter WR, Stürmer T, et al. Effect of adjuvant chemotherapy on survival of patients with stage III colon cancer diagnosed after age 75 years. J Clin Oncol. 2012;30:2624–2634.
   PubMed Web of Science ®Google Scholar
• Cen P, Liu C, Du XL. Comparison of toxicity profiles of fluorouracil versus oxaliplatin regimens in a large population-based cohort of elderly patients with colorectal cancer. Ann Oncol. 2012;23:1503–1511.
   PubMed Web of Science ®Google Scholar
• McKibbin T, Frei CR, Greene RE, et al. Disparities in the use of chemotherapy and monoclonal antibody therapy for elderly advanced colorectal cancer patients in the community oncology setting. Oncologist. 2008;13:876–885.
   PubMed Web of Science ®Google Scholar
• Cassidy J, Saltz LB, Giantonio BJ, et al. Effect of bevacizumab in older patients with metastatic colorectal cancer: pooled analysis of four randomized studies. J Cancer Res Clin Oncol. 2010;136:737–743.
   PubMed Web of Science ®Google Scholar
• Price TJ, Zannino D, Wilson K, 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;23:1531–1536.
   PubMed Web of Science ®Google Scholar
• Asmis Jehn TR, Powell E, Karapetis CS, 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;22:118–126.
   PubMed Web of Science ®Google Scholar
• Jehn CF, Böning L, Kröning H, et al. Cetuximab-based therapy in elderly comorbid patients with metastatic colorectal cancer. Br J Cancer. 2012;106:274–278.
   PubMed Web of Science ®Google Scholar
• Tournigand C, Andre T, Achille E, et al. FOLFIRI Followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol. 2004;22:229–237.
   PubMed Web of Science ®Google Scholar
• De Roock W, Claes B, Bernasconi D, et al. 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 Oncol. 2010;11:753–762.
   PubMed Web of Science ®Google Scholar
• Emambux S, Tachon G, Junca A, et al. Results and challenges of immune checkpoint inhibitors in colorectal cancer. Expert Opin Biol Ther. 2018;18:561–573.
   PubMed Web of Science ®Google Scholar
• Siena S, Sartore-Bianchi A, Marsoni S, et al. Targeting the human epidermal growth factor receptor 2 (HER2) oncogene in colorectal cancer. Ann Oncol. 2018;29:1108–1119.
   PubMed Web of Science ®Google Scholar