Can molecular biomarker-based patient selection in Phase I trials accelerate anticancer drug development?

Drug Discovery Today

Volumn 15, Issue 3-4, 2010, Pages 88-97

  Carden, Craig P ^a,b   Sarker, Debashis ^a   Postel Vinay, Sophie ^a   Yap, Timothy A ^a,b   Attard, Gerthardt ^a,b   Banerji, Udai ^a,b   Garrett, Michelle D ^b   Thomas, George V ^b   Workman, Paul ^b   Kaye, Stan B ^a,b   de Bono, Johann S ^a,b  

^a ROYAL MARSDEN HOSPITAL   (United Kingdom)

^b INSTITUTE OF CANCER RESEARCH   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

3 [1 (2,6 DICHLORO 3 FLUOROPHENYL)ETHOXY] 5 [1 (4 PIPERIDINYL) 1H PYRAZOL 4 YL] 2 PYRIDINYLAMINE; 7 ETHYL 10 HYDROXYCAMPTOTHECIN; ABIRATERONE ACETATE; B RAF KINASE; BCR ABL PROTEIN; DNA; EPIDERMAL GROWTH FACTOR RECEPTOR 2; ERLOTINIB; GEFITINIB; IRINOTECAN; KUDOS; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE INHIBITOR; OLAPARIB; PLACEBO; PLX 4032; PREDNISONE; SORAFENIB; TAMOXIFEN; TRASTUZUMAB; TUMOR MARKER; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; CANCER THERAPY; CLINICAL DECISION MAKING; CLINICAL TRIAL; COST EFFECTIVENESS ANALYSIS; DRUG APPROVAL; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG RESEARCH; DRUG RESPONSE; DRUG TARGETING; ENZYME INHIBITION; EVIDENCE BASED PRACTICE; FEASIBILITY STUDY; GENE EXPRESSION; GENE MUTATION; GENETIC POLYMORPHISM; GENETIC VARIABILITY; HIGH THROUGHPUT SCREENING; HUMAN; KIDNEY CARCINOMA; LUNG NON SMALL CELL CANCER; MEDICAL AUDIT; MELANOMA; MICROARRAY ANALYSIS; MOLECULAR IMAGING; OVARY CANCER; PATIENT SELECTION; PHARMACOGENOMICS; PROGNOSIS; PROSTATE CANCER; PROTEIN TARGETING; QUALITATIVE ANALYSIS; REVIEW; VALIDATION PROCESS;

ANTINEOPLASTIC AGENTS; BIOMARKERS, PHARMACOLOGICAL; CLINICAL TRIALS, PHASE I AS TOPIC; DRUG APPROVAL; DRUG DISCOVERY; HUMANS; MODELS, BIOLOGICAL; NEOPLASMS; PATIENT SELECTION; PHARMACOGENETICS;

EID: 75149113069     PISSN: 13596446     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.drudis.2009.11.006     Document Type: Review

References (104)

1. van Montfort R.L., and Workman P. Structure-based design of molecular cancer therapeutics. Trends Biotechnol. 27 (2009) 315-328
2. Collins I., and Workman P. New approaches to molecular cancer therapeutics. Nat. Chem. Biol. 2 (2006) 689-700
3. Hanahan D., and Weinberg R.A. The hallmarks of cancer. Cell 100 (2000) 57-70
4. Workman P., and de Bono J. Targeted therapeutics for cancer treatment: major progress towards personalised molecular medicine. Curr. Opin. Pharmacol. 8 (2008) 359-362
5. Stuart D., and Sellers W.R. Linking somatic genetic alterations in cancer to therapeutics. Curr. Opin. Cell Biol. 21 (2009) 304-310
6. Weinstein I.B., and Andrew J. Oncogene addiction. Cancer Res. 68 (2008) 4
7. Slamon D.J., et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N. Engl. J. Med. 344 (2001) 783-792
8. Demetri G.D., et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N. Engl. J. Med. 347 (2002) 472-480
9. Druker B.J., et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N. Engl. J. Med. 344 (2001) 1031-1037
10. Jones S., et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 321 (2008) 1801-1806
11. Cancer Genome Atlas Research Network. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455 (2008) 1061-1068
12. Wu J.M., et al. Heterogeneity of breast cancer metastases: comparison of therapeutic target expression and promoter methylation between primary tumors and their multifocal metastases. Clin. Cancer Res. 14 (2008) 1938-1946
13. Yegnasubramanian S., et al. DNA hypomethylation arises later in prostate cancer progression than CpG island hypermethylation and contributes to metastatic tumor heterogeneity. Cancer Res. 68 (2008) 8954-8967
14. Luo J., et al. Principles of cancer therapy: oncogene and non-oncogene addiction. Cell 136 (2009) 823-837
15. Workman P. The opportunities and challenges of personalized genome-based molecular therapies for cancer: targets, technologies, and molecular chaperones. Cancer Chemother. Pharmacol. 52 Suppl. 1 (2003) S45-S56
16. Bokemeyer C., et al. Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J. Clin. Oncol. 27 (2009) 663-671
17. Hecht J.R., et al. A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer. J. Clin. Oncol. 27 (2009) 672-680
18. Jimeno A., et al. KRAS mutations and sensitivity to epidermal growth factor receptor inhibitors in colorectal cancer: practical application of patient selection. J. Clin. Oncol. 27 (2009) 1130-1136
19. Tol J., et al. Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N. Engl. J. Med. 360 (2009) 563-572
20. Van Cutsem E., et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N. Engl. J. Med. 360 (2009) 1408-1417
21. Amado R.G., et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J. Clin. Oncol. 26 (2008) 1626-1634
22. Bokemeyer C., et al. KRAS status and efficacy of first-line treatment of patients with metastatic colorectal cancer (mCRC) with FOLFOX with or without cetuximab: the OPUS experience. J. Clin. Oncol. 26 Suppl. (2008) Abstract 4000
23. Van Cutsem E., et al. KRAS status and efficacy in the first-line treatment of patients with metastatic colorectal cancer (mCRC) treated with FOLFIRI with or without cetuximab: the CRYSTAL experience. J Clin. Oncol. 26 Suppl. (2008) Abstract 2
24. Kola I., and Landis J. Can the pharmaceutical industry reduce attrition rates?. Nat. Rev. Drug Discov. 3 (2004) 711-715
25. Kola I. The state of innovation in drug development. Clin. Pharmacol. Ther. 83 (2008) 227-230
26. Walker I., and Newell H. Do molecularly targeted agents in oncology have reduced attrition rates?. Nat. Rev. Drug Discov. 8 (2009) 15-16
27. DiMasi J.A., and Grabowski H.G. Economics of new oncology drug development. J. Clin. Oncol. 25 (2007) 209-216
28. Roberts Jr. T.G., et al. Trends in the risks and benefits to patients with cancer participating in phase 1 clinical trials. J. Am. Med. Assoc. 292 (2004) 2130-2140
29. Arkenau H.T., et al. Clinical outcome and prognostic factors for patients treated within the context of a phase I study: the Royal Marsden Hospital experience. Br. J. Cancer 98 (2008) 1029-1033
30. Italiano A., et al. Treatment outcome and survival in participants of phase I oncology trials carried out from 2003 to 2006 at Institut Gustave Roussy. Ann. Oncol. 19 (2008) 787-792
31. Goodsaid F., and Frueh F. Biomarker qualification pilot process at the US Food and Drug Administration. AAPS J. 9 (2007) E105-E108
32. Yu L.R., and Veenstra T.D. AACR-FDA-NCI cancer biomarkers collaborative. Expert Rev. Mol. Diagn. 7 (2007) 507-509
33. Sarker D., and Workman P. Pharmacodynamic biomarkers for molecular cancer therapeutics. Adv. Cancer Res. 96 (2007) 213-268
34. Sarker D., et al. Use of pharmacokinetic/pharmacodynamic biomarkers to support rational cancer drug development. Biomark. Med. 1 (2007) 18
35. Workman P. Using biomarkers in drug development. Clin. Adv. Hematol. Oncol. 4 (2006) 736-739
36. Workman P. Challenges of PK/PD measurements in modern drug development. Eur. J. Cancer 38 (2002) 2189-2193
37. Workman P. Auditing the pharmacological accounts for Hsp90 molecular chaperone inhibitors: unfolding the relationship between pharmacokinetics and pharmacodynamics. Mol. Cancer Ther. 2 (2003) 131-138
38. Workman P. How much gets there and what does it do?: the need for better pharmacokinetic and pharmacodynamic endpoints in contemporary drug discovery and development. Curr. Pharm. Des. 9 (2003) 891-902
39. Goulart B.H., et al. Trends in the use and role of biomarkers in phase I oncology trials. Clin. Cancer Res. 13 (2007) 6719-6726
40. Harris L., et al. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J. Clin. Oncol. 25 (2007) 5287-5312
41. Dowsett M., et al. Correlation between immunohistochemistry (HercepTest) and fluorescence in situ hybridization (FISH) for HER-2 in 426 breast carcinomas from 37 centres. J. Pathol. 199 (2003) 418-423
42. Cancer Research UK. Prognostic/Predictive Biomarker (BM) Roadmap (2009). http://science.cancerresearchuk.org/reps/pdfs/bidd_prognostic_roadmap.pdf (http://science.cancerresearchuk.org/reps/pdfs/bidd_prognostic_roadmap.pdf)
43. FDA. FDA/NCI/CMS Oncology Biomarker Qualification Initiative Memorandum of Understanding (2006). http://www.fda.gov/AboutFDA/PartnershipsCollaborations/MemorandaofUnderstandingMOUs/DomesticMOUs/ucm115681.html (http://www.fda.gov/AboutFDA/PartnershipsCollaborations/MemorandaofUnderstandingMOUs/DomesticMOUs/ucm115681.html)
44. Ratain M.J., and Glassman R.H. Biomarkers in phase I oncology trials: signal, noise, or expensive distraction?. Clin. Cancer Res. 13 (2007) 6545-6548
45. Carden C.P., et al. From darkness to light with biomarkers in early clinical trials of cancer drugs. Clin. Pharmacol. Ther. 85 (2009) 131-133
46. Escudier B., et al. Sorafenib for treatment of renal cell carcinoma: final efficacy and safety results of the Phase III treatment approaches in renal cancer global evaluation trial. J. Clin. Oncol 27 20 (2009) 3312-3318
47. Fukuoka M., et al. Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer (The IDEAL 1 Trial). J. Clin. Oncol. 21 (2003) 2237-2246
48. Cappuzzo F., et al. Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer. J. Natl. Cancer Inst. 97 (2005) 643-655
49. Kris M.G., et al. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. J. Am. Med. Assoc. 290 (2003) 2149-2158
50. Paez J.G., et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304 (2004) 1497-1500
51. Lynch T.J., et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N. Engl. J. Med. 350 (2004) 2129-2139
52. Engelman J.A., et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 316 (2007) 1039-1043
53. Fong P.C., et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N. Engl. J. Med. 361 (2009) 123-134
54. Farmer H., et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434 (2005) 917-921
55. Attard G., et al. Duplication of the fusion of TMPRSS2 to ERG sequences identifies fatal human prostate cancer. Oncogene 27 (2008) 253-263
56. Attard G., et al. Phase I clinical trial of a selective inhibitor of CYP17, abiraterone acetate, confirms that castration-resistant prostate cancer commonly remains hormone driven. J. Clin. Oncol. 26 (2008) 4563-4571
57. Yap T.A., et al. Targeting CYP17: established and novel approaches in prostate cancer. Curr. Opin. Pharmacol. 8 (2008) 449-457
58. Attard G., et al. Selective inhibition of CYP17 with abiraterone acetate is highly active in the treatment of castration-resistant prostate cancer. J. Clin. Oncol. 27 (2009) 3742-3748
59. Tomlins S.A., et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science 310 (2005) 644-648
60. Hermans K.G., et al. TMPRSS2:ERG fusion by translocation or interstitial deletion is highly relevant in androgen-dependent prostate cancer, but is bypassed in late-stage androgen receptor-negative prostate cancer. Cancer Res. 66 (2006) 6
61. Attard G., et al. Characterization of ERG, AR and PTEN gene status in circulating tumor cells from patients with castration-resistant prostate cancer. Cancer Res. 69 (2009) 2912-2918
62. Lim M.S., et al. The proteomic signature of NPM/ALK reveals deregulation of multiple cellular pathways. Blood (2009)
63. Soda M., et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 448 (2007) 561-566
64. Davies H., et al. Mutations of the BRAF gene in human cancer. Nature 417 (2002) 949-954
65. Karasarides M., et al. B-RAF is a therapeutic target in melanoma. Oncogene 23 (2004) 6292-6298
66. Sala E., et al. BRAF silencing by short hairpin RNA or chemical blockade by PLX4032 leads to different responses in melanoma and thyroid carcinoma cells. Mol. Cancer Res. 6 (2008) 751-759
67. Flaherty K., et al. Phase I study of PLX4032: proof of concept for V600E BRAF mutation as a therapeutic target in human cancer. J. Clin. Oncol. 27 Suppl. (2009) Abstract 9000
68. Puzanov I., et al. PLX4032, a highly selective V600E BRAF kinase inhibitor: clinical correlation of activity with pharmacokinetic and pharmacodynamic parameters in a phase I trial. J. Clin. Oncol. 27 Suppl. (2009) Abstract 9021
69. Solit D.B., et al. BRAF mutation predicts sensitivity to MEK inhibition. Nature 439 (2006) 358-362
70. Ji Y., et al. Dose-finding in phase I clinical trials based on toxicity probability intervals. Clin. Trials 4 (2007) 235-244
71. Cristofanilli M., et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N. Engl. J. Med. 351 (2004) 781-791
72. Maheswaran S., et al. Detection of mutations in EGFR in circulating lung-cancer cells. N. Engl. J. Med. 359 (2008) 366-377
73. Cohen S.J., et al. Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J. Clin. Oncol. 26 (2008) 3213-3221
74. de Bono J.S., et al. Potential applications for circulating tumor cells expressing the insulin-like growth factor-I receptor. Clin. Cancer Res. 13 (2007) 3611-3616
75. Shaffer D.R., et al. Circulating tumor cell analysis in patients with progressive castration-resistant prostate cancer. Clin. Cancer Res. 13 (2007) 2023-2029
76. Leversha M.A., et al. Fluorescence in situ hybridization analysis of circulating tumor cells in metastatic prostate cancer. Clin. Cancer Res. 15 (2009) 2091-2097
77. Tan D.S., and Reis-Filho J.S. Comparative genomic hybridisation arrays: high-throughput tools to determine targeted therapy in breast cancer. Pathobiology 75 (2008) 63-74
78. Thomas R.K., et al. High-throughput oncogene mutation profiling in human cancer. Nat. Genet. 39 (2007) 347-351
79. Ley T.J., et al. DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome. Nature 456 (2008) 66-72
80. van de Vijver M.J., et al. A gene-expression signature as a predictor of survival in breast cancer. N. Engl. J. Med. 347 (2002) 1999-2009
81. Saal L.H., et al. Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN tumor suppressor pathway activity. Proc. Natl. Acad. Sci. U. S. A. 104 (2007) 7564-7569
82. Waldman S.A., and Terzic A. MicroRNA signatures as diagnostic and therapeutic targets. Clin. Chem. 54 (2008) 943-944
83. Tibes R., et al. Reverse phase protein array: validation of a novel proteomic technology and utility for analysis of primary leukemia specimens and hematopoietic stem cells. Mol. Cancer Ther. 5 (2006) 2512-2521
84. Boyd Z.S., et al. Proteomic analysis of breast cancer molecular subtypes and biomarkers of response to targeted kinase inhibitors using reverse-phase protein microarrays. Mol. Cancer Ther. 7 (2008) 3695-3706
85. Mirzoeva O.K., et al. Basal subtype and MAPK/ERK kinase (MEK)-phosphoinositide 3-kinase feedback signaling determine susceptibility of breast cancer cells to MEK inhibition. Cancer Res. 69 (2009) 565-572
86. Van Beuningen R., et al. Use of flow-through peptide-microarrays for cell-lysate profiling. Proc. Am. Assoc. Cancer. Res. 47 (2006) Abstract 4635
87. Workman P., et al. Minimally invasive pharmacokinetic and pharmacodynamic technologies in hypothesis-testing clinical trials of innovative therapies. J. Natl. Cancer Inst. 98 (2006) 580-598
88. Smith-Jones P.M., et al. Imaging the pharmacodynamics of HER2 degradation in response to Hsp90 inhibitors. Nat. Biotechnol. 22 (2004) 701-706
89. 18F-fluoromisonidazole. Semin. Nucl. Med. 37 (2007) 451-461
90. Mullamitha S.A., et al. Phase I evaluation of a fully human anti-alphav integrin monoclonal antibody (CNTO 95) in patients with advanced solid tumors. Clin. Cancer Res. 13 (2007) 2128-2135
91. 123I-VEGF165). Biodistribution, safety and radiation dosimetry in patients with pancreatic carcinoma. Q. J. Nucl. Med. Mol. Imaging 48 (2004) 198-206
92. Czernin J., et al. Molecular imaging in the development of cancer therapeutics. Annu. Rev. Med. 57 (2006) 99-118
93. Jain K.K. Cancer biomarkers: current issues and future directions. Curr. Opin. Mol. Ther. 9 (2007) 563-571
94. Hylton N. Dynamic contrast-enhanced magnetic resonance imaging as an imaging biomarker. J. Clin. Oncol. 24 (2006) 3293-3298
95. Knopp M.V., et al. Pathophysiologic basis of contrast enhancement in breast tumors. J. Magn. Reson. Imaging 10 (1999) 260-266
96. Huang R.S., and Ratain M.J. Pharmacogenetics and pharmacogenomics of anticancer agents. CA Cancer J. Clin. 59 (2009) 42-55
97. Tan S.H., et al. Pharmacogenetics in breast cancer therapy. Clin. Cancer Res. 14 (2008) 8027-8041
98. Jin Y., et al. CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment. J. Natl. Cancer Inst. 97 (2005) 30-39
99. Goetz M.P., et al. Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flashes. J. Clin. Oncol. 23 (2005) 9312-9318
100. Innocenti F., et al. Genetic variants in the UDP-glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan. J. Clin. Oncol. 22 (2004) 1382-1388
101. Nagar S., and Remmel R.P. Uridine diphosphoglucuronosyltransferase pharmacogenetics and cancer. Oncogene 25 (2006) 1659-1672
102. Ramchandani R.P., et al. The role of SN-38 exposure. UGT1A1*28 polymorphism, and baseline bilirubin level in predicting severe irinotecan toxicity. J. Clin. Pharmacol. 47 (2007) 78-86
103. Snozek C.L., et al. LDLR promoter variant and exon 14 mutation on the same chromosome are associated with an unusually severe FH phenotype and treatment resistance. Eur. J. Hum. Genet. 17 (2009) 85-90
104. Evans W.E., and McLeod H.L. Pharmacogenomics - drug disposition, drug targets, and side effects. N. Engl. J. Med. 348 (2003) 538-549