The importance of molecular markers for diagnosis and selection of targeted treatments in patients with cancer

Journal of Internal Medicine

Volumn 278, Issue 6, 2015, Pages 545-570

  Tobin, N P ^a   Foukakis, T ^a   De Petris, L ^a   Bergh, J ^a  

^a KAROLINSKA INSTITUTE   (Sweden)

Author keywords

Breast; Colon; Gene expression; Immunohistochemistry; Lung; Next generation sequencing

Indexed keywords

MOLECULAR MARKER; TRANSCRIPTOME; TUMOR MARKER;

BREAST CANCER; CANCER DIAGNOSIS; CANCER INCIDENCE; CANCER MORTALITY; CANCER THERAPY; COLORECTAL CANCER; DNA SEQUENCE; GENE EXPRESSION; HUMAN; IMMUNOHISTOCHEMISTRY; LUNG CANCER; MOLECULARLY TARGETED THERAPY; NEXT GENERATION SEQUENCING; PRIORITY JOURNAL; REVIEW; BREAST NEOPLASMS; CANCER STAGING; COLORECTAL NEOPLASMS; FEMALE; GENETICS; LUNG NEOPLASMS; MALE; METASTASIS; PATHOLOGY; PATIENT SELECTION; PHARMACOGENETICS; PROCEDURES;

BIOMARKERS, TUMOR; BREAST NEOPLASMS; COLORECTAL NEOPLASMS; FEMALE; HUMANS; LUNG NEOPLASMS; MALE; MOLECULAR TARGETED THERAPY; NEOPLASM METASTASIS; NEOPLASM STAGING; PATIENT SELECTION; PHARMACOGENETICS; TRANSCRIPTOME;

EID: 84955189295     PISSN: 09546820     EISSN: 13652796     Source Type: Journal    
DOI: 10.1111/joim.12429     Document Type: Review

References (176)

1. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144: 646-74.
2. Holohan C, Van Schaeybroeck S, Longley DB, Johnston PG. Cancer drug resistance: an evolving paradigm. Nat Rev Cancer 2013; 13: 714-26.
3. Beatson GT. On treatment of inoperable cases of carcinoma of the mamma: suggestions for a new method of treatment with illustrative cases. Lancet 1896; 2: 104-7.
4. Weiner LM, Surana R, Wang S. Monoclonal antibodies: versatile platforms for cancer immunotherapy. Nat Rev Immunol 2010; 10: 317-27.
5. Zhang J, Yang PL, Gray NS. Targeting cancer with small molecule kinase inhibitors. Nat Rev Cancer 2009; 9: 28-39.
6. Czajkowsky DM, Hu J, Shao Z, Pleass RJ. Fc-fusion proteins: new developments and future perspectives. EMBO Mol Med 2012; 4: 1015-28.
7. Hoadley KA, Yau C, Wolf DM et al. Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin. Cell 2014; 158: 929-44.
8. Dowsett M, Sestak I, Lopez-Knowles E et al. Comparison of PAM50 risk of recurrence score with oncotype DX and IHC4 for predicting risk of distant recurrence after endocrine therapy. J Clin Oncol 2013; 31: 2783-90.
9. Schena M, Shalon D, Davis RW, Brown PO. Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 1995; 270: 467-70.
10. Perou CM, Sørlie T, Eisen MB et al. Molecular portraits of human breast tumours. Nature 2000; 406: 747-52.
11. Van't Veer LJ, Dai H, van de Vijver MJ et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature 2002; 415: 530-6.
12. Valk PJM, Verhaak RGW, Beijen MA et al. Prognostically useful gene-expression profiles in acute myeloid leukemia. N Engl J Med 2004; 350: 1617-28.
13. Chibon F, Lagarde P, Salas S et al. Validated prediction of clinical outcome in sarcomas and multiple types of cancer on the basis of a gene expression signature related to genome complexity. Nat Med 2010; 16: 781-7.
14. Hoshida Y, Villanueva A, Kobayashi M et al. Gene expression in fixed tissues and outcome in hepatocellular carcinoma. N Engl J Med 2008; 359: 1995-2004.
15. Oberli A, Popovici V, Delorenzi M et al. Expression profiling with RNA from formalin-fixed, paraffin-embedded material. BMC Med Genomics 2008; 1: 9.
16. Mittempergher L, de Ronde JJ, Nieuwland M et al. Gene expression profiles from formalin fixed paraffin embedded breast cancer tissue are largely comparable to fresh frozen matched tissue. PLoS One 2011; 6: e17163.
17. Chibon F. Cancer gene expression signatures - the rise and fall? Eur J Cancer 2013; 49: 2000-9.
18. Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A 1977; 74: 5463-7.
19. Chmielecki J, Meyerson M. DNA sequencing of cancer: what have we learned? Annu Rev Med 2014; 65: 63-79.
20. Shendure J, Ji H. Next-generation DNA sequencing. Nat Biotechnol 2008; 26: 1135-45.
21. Robert NJ, Diéras V, Glaspy J et al. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol 2011; 29: 1252-60.
22. Miller K, Wang M, Gralow J et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 2007; 357: 2666-76.
23. Gilbert MR, Dignam JJ, Armstrong TS et al. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med 2014; 370: 699-708.
24. Chinot OL, Wick W, Mason W et al. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med 2014; 370: 709-22.
25. European Medicines Agency. Scientific conclusions and grounds for refusal of the variation presented by the European Medicines Agency.
26. Bray F, Jemal A, Grey N, Ferlay J, Forman D. Global cancer transitions according to the Human Development Index (2008-2030): a population-based study. Lancet Oncol 2012; 13: 790-801.
27. Ferlay J, Soerjomataram I, Dikshit R et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012: Globocan 2012. Int J Cancer 2015; 136: E359-86.
28. Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol 2006; 24: 2137-50.
29. Forouzanfar MH, Foreman KJ, Delossantos AM et al. Breast and cervical cancer in 187 countries between 1980 and 2010: a systematic analysis. Lancet 2011; 378: 1461-84.
30. Berry DA, Cronin KA, Plevritis SK et al. Effect of screening and adjuvant therapy on mortality from breast cancer. N Engl J Med 2005; 353: 1784-92.
31. Reis L, Melbert D, Krapcho M et al. SEER cancer statistics review, 1975-2005. Natl Cancer Inst Bethesda, MD, http://seer.cancer.gov/csr/1975_2005/, based on November 2007 SEER data submission, posted to the SEER web site, 2008.
32. Verdecchia A, Francisci S, Brenner H et al. Recent cancer survival in Europe: a 2000-02 period analysis of EUROCARE-4 data. Lancet Oncol 2007; 8: 784-96.
33. Foukakis T, Fornander T, Lekberg T, Hellborg H, Adolfsson J, Bergh J. Age-specific trends of survival in metastatic breast cancer: 26 years longitudinal data from a population-based cancer registry in Stockholm, Sweden. Breast Cancer Res Treat 2011; 130: 553-60.
34. Foukakis T, Bergh J. Prognostic and predictive factors in early, non-metastatic breast cancer. Dizon Ed UpToDate Waltham, MA.
35. Harvey JM, Clark GM, Osborne CK, Allred DC. Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J Clin Oncol 1999; 17: 1474-81.
36. Ravdin PM, Siminoff LA, Davis GJ et al. Computer program to assist in making decisions about adjuvant therapy for women with early breast cancer. J Clin Oncol 2001; 19: 980-91.
37. Michaelson JS, Chen LL, Bush D, Fong A, Smith B, Younger J. Improved web-based calculators for predicting breast carcinoma outcomes. Breast Cancer Res Treat 2011; 128: 827-35.
38. Lundin J, Lundin M, Isola J, Joensuu H. A web-based system for individualised survival estimation in breast cancer. BMJ 2003; 326: 29.
39. De Azambuja E, Cardoso F, de Castro Jr G et al. Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12, 155 patients. Br J Cancer 2007; 96: 1504-13.
40. Stuart-Harris R, Caldas C, Pinder SE, Pharoah P. Proliferation markers and survival in early breast cancer: a systematic review and meta-analysis of 85 studies in 32, 825 patients. Breast 2008; 17: 323-34.
41. Harris L, Fritsche H, Mennel R et al. American society of clinical oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol 2007; 25: 5287-312.
42. Senkus E, Kyriakides S, Penault-Llorca F et al. Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013; 24: vi7-23.
43. Paik S, Shak S, Tang G et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 2004; 351: 2817-26.
44. Paik S, Tang G, Shak S et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol 2006; 24: 3726-34.
45. Sørlie T, Perou CM, Tibshirani R et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 2001; 98: 10869-74.
46. Parker JS, Mullins M, Cheang MCU et al. Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol 2009; 27: 1160-7.
47. Wang Y, Klijn JG, Zhang Y et al. Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet 2005; 365: 671-9.
48. Ma X-J, Wang Z, Ryan PD et al. A two-gene expression ratio predicts clinical outcome in breast cancer patients treated with tamoxifen. Cancer Cell 2004; 5: 607-16.
49. Filipits M, Rudas M, Jakesz R et al. A new molecular predictor of distant recurrence in ER-positive, HER2-negative breast cancer adds independent information to conventional clinical risk factors. Clin Cancer Res 2011; 17: 6012-20.
50. Miller LD, Smeds J, George J et al. An expression signature for p53 status in human breast cancer predicts mutation status, transcriptional effects, and patient survival. Proc Natl Acad Sci U S A 2005; 102: 13550-5.
51. Ivshina AV, George J, Senko O et al. Genetic reclassification of histologic grade delineates new clinical subtypes of breast cancer. Cancer Res 2006; 66: 10292-301.
52. Sotiriou C, Wirapati P, Loi S et al. Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis. J Natl Cancer Inst 2006; 98: 262-72.
53. Tobin NP, Lindström LS, Carlson JW, Bjöhle J, Bergh J, Wennmalm K. Multi-level gene expression signatures, but not binary, outperform Ki67 for the long term prognostication of breast cancer patients. Mol Oncol 2014; 8: 741-52.
54. Loi S, Haibe-Kains B, Desmedt C et al. Definition of clinically distinct molecular subtypes in estrogen receptor-positive breast carcinomas through genomic grade. J Clin Oncol 2007; 25: 1239-46.
55. Cheang MCU, Chia SK, Voduc D et al. Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst 2009; 101: 736-50.
56. Lindstrom LS, Karlsson E, Wilking UM et al. Clinically used breast cancer markers such as estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 are unstable throughout tumor progression. J Clin Oncol 2012; 30: 2601-8.
57. Niikura N, Liu J, Hayashi N et al. Loss of human epidermal growth factor receptor 2 (HER2) expression in metastatic sites of HER2-overexpressing primary breast tumors. J Clin Oncol 2011; 30: 593-9.
58. Thompson AM, Jordan LB, Quinlan P et al. Prospective comparison of switches in biomarker status between primary and recurrent breast cancer: the Breast Recurrence In Tissues Study (BRITS). Breast Cancer Res 2010; 12: R92.
59. Tobin NP, Harrell JC, Lövrot J et al. Molecular subtype and tumor characteristics of breast cancer metastases as assessed by gene expression significantly influence patient post-relapse survival. Ann Oncol 2015; 26: 81-8.
60. Davies C, Godwin J, Gray R et al. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet 2011; 378: 771-84.
61. Howell A, Bergh J. Insights into the place of fulvestrant for the treatment of advanced endocrine responsive breast cancer. J Clin Oncol 2010; 28: 4548-50.
62. Dowsett M, Cuzick J, Ingle J et al. Meta-analysis of breast cancer outcomes in adjuvant trials of aromatase inhibitors versus tamoxifen. J Clin Oncol 2010; 28: 509-18.
63. Gibson L, Lawrence D, Dawson C, Bliss J. Aromatase inhibitors for treatment of advanced breast cancer in postmenopausal women. Cochrane Database Syst Rev 2009; (4): CD003370.
64. Mehta RS, Barlow WE, Albain KS et al. Combination anastrozole and fulvestrant in metastatic breast cancer. N Engl J Med 2012; 367: 435-44.
65. Bergh J, Jönsson P-E, Lidbrink EK et al. FACT: an open-label randomized phase III study of fulvestrant and anastrozole in combination compared with anastrozole alone as first-line therapy for patients with receptor-positive postmenopausal breast cancer. J Clin Oncol 2012; 30: 1919-25.
66. Leo AD, Jerusalem G, Petruzelka L et al. Final overall survival: fulvestrant 500 mg vs 250 mg in the randomized CONFIRM trial. J Natl Cancer Inst 2014; 106: djt337.
67. Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature 2012; 490: 61-70.
68. Toy W, Shen Y, Won H et al. ESR1 ligand-binding domain mutations in hormone-resistant breast cancer. Nat Genet 2013; 45: 1439-45.
69. Robinson DR, Wu Y-M, Vats P et al. Activating ESR1 mutations in hormone-resistant metastatic breast cancer. Nat Genet 2013; 45: 1446-51.
70. Karlsson E, Appelgren J, Solterbeck A, Bergenheim M, Alvariza V, Bergh J. Breast cancer during follow-up and progression - a population based cohort on new cancers and changed biology. Eur J Cancer 2014; 50: 2916-24.
71. Piccart-Gebhart MJ, Procter M, Leyland-Jones B et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 2005; 353: 1659-72.
72. Romond EH, Perez EA, Bryant J et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 2005; 353: 1673-84.
73. Goldhirsch A, Gelber RD, Piccart-Gebhart MJ et al. 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial. Lancet 2013; 382: 1021-8.
74. Perez EA, Romond EH, Suman VJ et al. Four-year follow-up of trastuzumab plus adjuvant chemotherapy for operable human epidermal growth factor receptor 2-positive breast cancer: joint analysis of data from NCCTG N9831 and NSABP B-31. J Clin Oncol 2011; 29: 3366-73.
75. Slamon DJ, Leyland-Jones B, Shak S et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001; 344: 783-92.
76. Marty M, Cognetti F, Maraninchi D et al. Randomized Phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J Clin Oncol 2005; 23: 4265-74.
77. Verma S, Miles D, Gianni L et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 2012; 367: 1783-91.
78. Pivot X, Manikhas A, Zurawski B et al. CEREBEL (EGF111438): a Phase III, randomized, open-label study of lapatinib plus capecitabine versus trastuzumab plus capecitabine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol 2015; 33: 1564-73.
79. Gelmon KA, Boyle F, Kaufman B et al. Open-label phase III randomized controlled trial comparing taxane-based chemotherapy (Tax) with lapatinib (L) or trastuzumab (T) as first-line therapy for women with HER2+ metastatic breast cancer: Interim analysis (IA) of NCIC CTG MA.31/GSK EGF 108919. J Clin Oncol 2012; ASCO Annual Meeting Abstracts. 30 No 15_suppl (May 20 Supplement), 2012: LBA671.
80. Gianni L, Pienkowski T, Im Y-H et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol 2012; 13: 25-32.
81. De Azambuja E, Holmes AP, Piccart-Gebhart M et al. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol 2014; 15: 1137-46.
82. Swain SM, Baselga J, Kim S-B et al. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med 2015; 372: 724-34.
83. Blackwell KL, Burstein HJ, Storniolo AM et al. Overall survival benefit with lapatinib in combination with trastuzumab for patients with human epidermal growth factor receptor 2-positive metastatic breast cancer: final results from the EGF104900 Study. J Clin Oncol 2012; 30: 2585-92.
84. Cortazar P, Zhang L, Untch M et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 2014; 384: 164-72.
85. Berruti A, Amoroso V, Gallo F et al. Pathologic complete response as a potential surrogate for the clinical outcome in patients with breast cancer after neoadjuvant therapy: a meta-regression of 29 randomized prospective studies. J Clin Oncol 2014; 32: 3883-92.
86. Bang Y-J, Van Cutsem E, Feyereislova A et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 2010; 376: 687-97.
87. Baselga J, Campone M, Piccart M et al. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med 2012; 366: 520-9.
88. Piccart M, Hortobagyi G, Campone M, Pritchard K, Noguchi S, Rugo H. Overall survival results from BOLERO-2. Present EBCC-9, 2014.
89. Hemel D, Domchek SM. Breast cancer predisposition syndromes. Hematol Oncol Clin North Am 2010; 24: 799-814.
90. Tutt A, Ellis P, Kilburn L et al. The TNT trial: a randomized phase III trial of carboplatin (C) compared with docetaxel (D) for patients with metastatic or recurrent locally advanced triple negative or BRCA1/2 breast cancer (CRUK/07/012). SABCS, 2014 [abstract S3-01].
91. Oza AM, Cibula D, Benzaquen AO et al. Olaparib combined with chemotherapy for recurrent platinum-sensitive ovarian cancer: a randomised phase 2 trial. Lancet Oncol 2015; 16: 87-97.
92. Wang TC, Cardiff RD, Zukerberg L, Lees E, Arnold A, Schmidt EV. Mammary hyperplasia and carcinoma in MMTV-cyclin D1 transgenic mice. Nature 1994; 369: 669-71.
93. Buckley MF, Sweeney KJ, Hamilton JA et al. Expression and amplification of cyclin genes in human breast cancer. Oncogene 1993; 8: 2127-33.
94. Finn RS, Crown JP, Lang I et al. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol 2015; 16: 25-35.
95. Labianca R, Nordlinger B, Beretta GD et al. Early colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013; 24: vi64-72.
96. Hong YS, Nam B-H, Kim K-P et al. Oxaliplatin, fluorouracil, and leucovorin versus fluorouracil and leucovorin as adjuvant chemotherapy for locally advanced rectal cancer after preoperative chemoradiotherapy (ADORE): an open-label, multicentre, phase 2, randomised controlled trial. Lancet Oncol 2014; 15: 1245-53.
97. 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: 2938-47.
98. Grothey A, Sargent D, Goldberg RM, Schmoll H-J. Survival of patients with advanced colorectal cancer improves with the availability of fluorouracil-leucovorin, irinotecan, and oxaliplatin in the course of treatment. J Clin Oncol 2004; 22: 1209-14.
99. Taieb J, Tabernero J, Mini E et al. Oxaliplatin, fluorouracil, and leucovorin with or without cetuximab in patients with resected stage III colon cancer (PETACC-8): an open-label, randomised phase 3 trial. Lancet Oncol 2014; 15: 862-73.
100. Alberts SR, Sargent DJ, Nair S et al. Effect of oxaliplatin, fluorouracil, and leucovorin with or without cetuximab on survival among patients with resected stage III colon cancer: a randomized trial. JAMA 2012; 307: 1383-93.
101. De Gramont A, Van Cutsem E, Schmoll H-J et al. Bevacizumab plus oxaliplatin-based chemotherapy as adjuvant treatment for colon cancer (AVANT): a phase 3 randomised controlled trial. Lancet Oncol 2012; 13: 1225-33.
102. Allegra CJ, Yothers G, O'Connell MJ et al. Phase III trial assessing bevacizumab in stages II and III carcinoma of the colon: results of NSABP protocol C-08. J Clin Oncol 2011; 29: 11-6.
103. Uehara K, Hiramatsu K, Maeda A et al. Neoadjuvant oxaliplatin and capecitabine and bevacizumab without radiotherapy for poor-risk rectal cancer: N-SOG 03 Phase II trial. Jpn J Clin Oncol 2013; 43: 964-71.
104. Maru D, Venook AP, Ellis LM. Predictive biomarkers for bevacizumab: are we there yet? Clin Cancer Res 2013; 19: 2824-7.
105. Gordon MS, Margolin K, Talpaz M et al. Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer. J Clin Oncol 2001; 19: 843-50.
106. Hurwitz H, Fehrenbacher L, Novotny W et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004; 350: 2335-42.
107. Saltz LB, Clarke S, Díaz-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: 2013-9.
108. 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: 1077-85.
109. 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: 3191-8.
110. Loupakis F, Cremolini C, Masi G et al. Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer. N Engl J Med 2014; 371: 1609-18.
111. Pericay C, Folprecht G, Saunders M et al. Phase 2 randomized, noncomparative open-label study of aflibercept and modified FOLFOX6 in the first line treatment of metastatic colorectal cancer (AFFIRM). Ann Oncol 2012; 23 (abstract O-0024): iv5-18.
112. Van Cutsem E, Tabernero J, Lakomy R 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: 3499-506.
113. Oda K, Matsuoka Y, Funahashi A, Kitano H. A comprehensive pathway map of epidermal growth factor receptor signaling. Mol Syst Biol 2005; 1: 25.0010 (Epub 2005 May 25).
114. Citri A, Yarden Y. EGF-ERBB signalling: towards the systems level. Nat Rev Mol Cell Biol 2006; 7: 505-16.
115. Cunningham D, Humblet Y, Siena S et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 2004; 351: 337-45.
116. Douillard J-Y, Siena S, Cassidy J et al. 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 Oncol 2010; 28: 4697-705.
117. Lièvre A, Bachet J-B, Boige V et al. KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol 2008; 26: 374-9.
118. Amado RG, Wolf M, Peeters M et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 2008; 26: 1626-34.
119. Douillard J-Y, Oliner KS, Siena S et al. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med 2013; 369: 1023-34.
120. Van Cutsem E, Lenz H-J, Köhne C-H et al. Fluorouracil, leucovorin, and irinotecan plus cetuximab treatment and RAS mutations in colorectal cancer. J Clin Oncol 2015; 33: 692-700.
121. Bokemeyer C, Kohne C-H, Ciardiello F et al. Treatment outcome according to tumor RAS mutation status in OPUS study patients with metastatic colorectal cancer (mCRC) randomized to FOLFOX4 with/without cetuximab. J Clin Oncol 2014; 32: 5s.
122. Van Cutsem E, Cervantes A, Nordlinger B, Arnold D, On behalf of the ESMO Guidelines Working Group. Metastatic colorectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2014; 25: iii1-9.
123. Van Cutsem E, Köhne C-H, Hitre E et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 2009; 360: 1408-17.
124. Peeters M, Price TJ, Cervantes A et al. 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 Oncol 2010; 28: 4706-13.
125. Sobrero AF, Maurel J, Fehrenbacher L 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: 2311-9.
126. 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: 1065-75.
127. Venook AP, Niedzwiecki D, Lenz H-J et al. 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). J Clin Oncol 2014; 32: 5s.
128. Wilhelm SM, Dumas J, Adnane L et al. Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. Int J Cancer 2011; 129: 245-55.
129. Li J, Qin S, Yau T et al. O-0023concur: a randomized, double-blind, placebo-controlled Phase 3 study of regorafenib monotherapy in asian patients with previously treated metastatic colorectal cancer (mcrc). Ann Oncol 2014; 25: ii114-5.
130. Grothey A, Van Cutsem E, Sobrero A et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013; 381: 303-12.
131. Hubbard JM, Grothey A. Colorectal cancer in 2014: progress in defining first-line and maintenance therapies. Nat Rev Clin Oncol 2015; 12: 73-4.
132. Clancy C, Burke JP, Kalady MF, Coffey JC. BRAF mutation is associated with distinct clinicopathological characteristics in colorectal cancer: a systematic review and meta-analysis. Colorectal Dis 2013; 15: e711-8.
133. Safaee Ardekani G, Jafarnejad SM, Tan L, Saeedi A, Li G. The prognostic value of BRAF mutation in colorectal cancer and melanoma: a systematic review and meta-analysis. PLoS One 2012; 7: e47054.
134. Seymour MT, Brown SR, Middleton G et al. Panitumumab and irinotecan versus irinotecan alone for patients with KRAS wild-type, fluorouracil-resistant advanced colorectal cancer (PICCOLO): a prospectively stratified randomised trial. Lancet Oncol 2013; 14: 749-59.
135. Chapman PB, Hauschild A, Robert C et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 2011; 364: 2507-16.
136. Kopetz S, Desai J, Chan E et al. PLX4032 in metastatic colorectal cancer patients with mutant BRAF tumors. J Clin Oncol 2010; 28: 15s.
137. 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: 1893-901.
138. Hinoue T, Weisenberger DJ, Lange CPE et al. Genome-scale analysis of aberrant DNA methylation in colorectal cancer. Genome Res 2012; 22: 271-82.
139. Walther A, Johnstone E, Swanton C, Midgley R, Tomlinson I, Kerr D. Genetic prognostic and predictive markers in colorectal cancer. Nat Rev Cancer 2009; 9: 489-99.
140. De Sousa E, Melo F, Wang X, Jansen M et al. Poor-prognosis colon cancer is defined by a molecularly distinct subtype and develops from serrated precursor lesions. Nat Med 2013; 19: 614-8.
141. Sadanandam A, Lyssiotis CA, Homicsko K et al. A colorectal cancer classification system that associates cellular phenotype and responses to therapy. Nat Med 2013; 19: 619-25.
142. Cancer Genome Atlas Network. Comprehensive molecular characterization of human colon and rectal cancer. Nature 2012; 487: 330-7.
143. Marisa L, de Reyniès A, Duval A et al. Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value. PLoS Med 2013; 10: e1001453.
144. Haan JC, Labots M, Rausch C et al. Genomic landscape of metastatic colorectal cancer. Nat Commun 2014; 5: 5457.
145. Linnekamp JF, Wang X, Medema JP, Vermeulen L. Colorectal cancer heterogeneity and targeted therapy: a case for molecular disease subtypes. Cancer Res 2015; 75: 245-9.
146. Sadanandam A, Wang X, de Sousa E, Melo F et al. Reconciliation of classification systems defining molecular subtypes of colorectal cancer: interrelationships and clinical implications. Cell Cycle 2014; 13: 353-7.
147. Reck M, Popat S, Reinmuth N et al. Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2014; 25(Suppl 3): iii27-39.
148. Lynch TJ, Bell DW, Sordella R et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004; 350: 2129-39.
149. Zhou C, Wu Y-L, Chen G et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol 2011; 12: 735-42.
150. Rosell R, Carcereny E, Gervais R et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol 2012; 13: 239-46.
151. Wu Y-L. First-line erlotinib versus cisplatin/gemcitabine (gp) in patients with advanced egfr mutation-positive nonsmall-cell lung cancer (nsclc): interim analyses from the phase 3, open-label, ENSURE study. World Conf Lung Cancer, 2013, [poster P1.11-021].
152. Mok TS, Wu Y-L, Thongprasert S et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361: 947-57.
153. Maemondo M, Inoue A, Kobayashi K et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 2010; 362: 2380-8.
154. Mitsudomi T, Morita S, Yatabe Y et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol 2010; 11: 121-8.
155. Sequist LV, Yang JC-H, Yamamoto N et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol 2013; 31: 3327-34.
156. Wu Y-L, Zhou C, Hu C-P et al. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol 2014; 15: 213-22.
157. Yang JC-H, Wu Y-L, Schuler M et al. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol 2015; 16: 141-51.
158. Seto T, Kato T, Nishio M et al. Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study. Lancet Oncol 2014; 15: 1236-44.
159. Steuer CE, Khuri FR, Ramalingam SS. The next generation of epidermal growth factor receptor tyrosine kinase inhibitors in the treatment of lung cancer. Cancer 2015; 121: E1-6.
160. Thunnissen E, Bubendorf L, Dietel M et al. EML4-ALK testing in non-small cell carcinomas of the lung: a review with recommendations. Virchows Arch 2012; 461: 245-57.
161. Shaw AT, Kim D-W, Nakagawa K et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med 2013; 368: 2385-94.
162. Solomon BJ, Mok T, Kim D-W et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med 2014; 371: 2167-77.
163. Camidge DR, Pao W, Sequist LV. Acquired resistance to TKIs in solid tumours: learning from lung cancer. Nat Rev Clin Oncol 2014; 11: 473-81.
164. Shaw AT, Kim D-W, Mehra R et al. Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med 2014; 370: 1189-97.
165. Shaw AT, Ou S-HI, Bang Y-J et al. Crizotinib in ROS1-rearranged non-small-cell lung cancer. N Engl J Med 2014; 371: 1963-71.
166. Marchetti A, Felicioni L, Malatesta S et al. Clinical features and outcome of patients with non-small-cell lung cancer harboring BRAF mutations. J Clin Oncol 2011; 29: 3574-9.
167. Planchard D, Kim T, Mazières J et al. Dabrafenib in patients with BRAF V600E-mutant advanced non-small cell lung cancer (NSCLC): a multicenter, open-label, phase II trial (BRF113928). Ann Oncol 2014; 25 [abstract LBA38_PR]: v1-41.
168. Wang R, Hu H, Pan Y et al. RET fusions define a unique molecular and clinicopathologic subtype of non-small-cell lung cancer. J Clin Oncol 2012; 30: 4352-9.
169. Gautschi O, Zander T, Keller FA et al. A patient with lung adenocarcinoma and RET fusion treated with vandetanib. J Thorac Oncol 2013; 8: e43-4.
170. Nivolumab approved for lung cancer. Cancer Discov 2015; 5: OF1.
171. Jonsson B, Bergh J. Hurdles in anticancer drug development from a regulatory perspective. Nat Rev Clin Oncol 2012; 9: 236-43.
172. Alexandrov LB, Nik-Zainal S, Wedge DC, Campbell PJ, Stratton MR. Deciphering signatures of mutational processes operative in human cancer. Cell Rep 2013; 3: 246-59.
173. Nik-Zainal S, Alexandrov LB, Wedge DC et al. Mutational processes molding the genomes of 21 breast cancers. Cell 2012; 149: 979-93.
174. Gerlinger M, Rowan AJ, Horswell S et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 2012; 366: 883-92.
175. Bergh J. Quo vadis with targeted drugs in the 21st century? J Clin Oncol 2009; 27: 2-5.
176. Ellis MJ, Ding L, Shen D et al. Whole-genome analysis informs breast cancer response to aromatase inhibition. Nature 2012; 486: 353-60.