U.S. flag

An official website of the United States government

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Brown LC, Fisher D, Adams R, et al. Molecular selection of therapy in metastatic colorectal cancer: the FOCUS4 molecularly stratified RCT [Internet]. Southampton (UK): National Institute for Health and Care Research; 2022 Dec. (Efficacy and Mechanism Evaluation, No. 9.9.)

Cover of Molecular selection of therapy in metastatic colorectal cancer: the FOCUS4 molecularly stratified RCT

Molecular selection of therapy in metastatic colorectal cancer: the FOCUS4 molecularly stratified RCT [Internet].

Show details

References

1.
Cancer Research UK. Cancer Statistics for the UK. URL: www​.cancerresearchuk​.org/health-professional​/cancer-statistics-for-the-uk (accessed 15 November 2022).
2.
Xie YH, Chen YX, Fang JY. Comprehensive review of targeted therapy for colorectal cancer. Signal Transduct Target Ther 2020;5:22. 10.1038/s41392-020-0116-z [PMC free article: PMC7082344] [PubMed: 32296018] [CrossRef]
3.
De Roock W, Claes B, Bernasconi D, De Schutter J, Biesmans B, Fountzilas G, 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;11:753–62. 10.1016/S1470-2045(10)70130-3 [PubMed: 20619739] [CrossRef]
4.
Freidlin B, Sun Z, Gray R, Korn EL. Phase III clinical trials that integrate treatment and biomarker evaluation. J Clin Oncol 2013;31:3158–61. 10.1200/JCO.2012.48.3826 [PMC free article: PMC3753704] [PubMed: 23569306] [CrossRef]
5.
Popovici V, Budinska E, Tejpar S, Weinrich S, Estrella H, Hodgson G, et al. Identification of a poor-prognosis BRAF-mutant-like population of patients with colon cancer. J Clin Oncol 2012;30:1288–95. 10.1200/JCO.2011.39.5814 [PubMed: 22393095] [CrossRef]
6.
Maughan TS, Adams RA, Smith CG, Meade AM, Seymour MT, Wilson RH, et al. Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet 2011;377:2103–14. 10.1016/S0140-6736(11)60613-2 [PMC free article: PMC3159415] [PubMed: 21641636] [CrossRef]
7.
The Cancer Genome Atlas Network. Comprehensive molecular characterization of human colon and rectal cancer. Nature 2012;487:330–7. 10.1038/nature11252 [PMC free article: PMC3401966] [PubMed: 22810696] [CrossRef]
8.
Roth AD, Tejpar S, Delorenzi M, Yan P, Fiocca R, Klingbiel D, et al. Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC-3, EORTC 40993, SAKK 60-00 trial. J Clin Oncol 2010;28:466–74. 10.1200/JCO.2009.23.3452 [PubMed: 20008640] [CrossRef]
9.
Wasan H, Meade AM, Adams R, Wilson R, Pugh C, Fisher D, et al. Intermittent chemotherapy plus either intermittent or continuous cetuximab for first-line treatment of patients with KRAS wild-type advanced colorectal cancer (COIN-B): a randomised phase 2 trial. Lancet Oncol 2014;15:631–9. 10.1016/S1470-2045(14)70106-8 [PMC free article: PMC4012566] [PubMed: 24703531] [CrossRef]
10.
Parmar MK, Barthel FM, Sydes M, Langley R, Kaplan R, Eisenhauer E, et al. Speeding up the evaluation of new agents in cancer. J Natl Cancer Inst 2008;100:1204–14. 10.1093/jnci/djn267 [PMC free article: PMC2528020] [PubMed: 18728279] [CrossRef]
11.
Royston P, Barthel FM, Parmar MK, Choodari-Oskooei B, Isham V. Designs for clinical trials with time-to-event outcomes based on stopping guidelines for lack of benefit. Trials 2011;12:81. 10.1186/1745-6215-12-81 [PMC free article: PMC3078872] [PubMed: 21418571] [CrossRef]
12.
Royston P, Parmar MK, Qian W. Novel designs for multi-arm clinical trials with survival outcomes with an application in ovarian cancer. Stat Med 2003;22:2239–56. 10.1002/sim.1430 [PubMed: 12854091] [CrossRef]
13.
Kaplan R, Maughan T, Crook A, Fisher D, Wilson R, Brown L, Parmar M. Evaluating many treatments and biomarkers in oncology: a new design. J Clin Oncol 2013;31:4562–8. 10.1200/JCO.2013.50.7905 [PMC free article: PMC4394353] [PubMed: 24248692] [CrossRef]
14.
Lièvre A, Bachet JB, Le Corre D, Boige V, Landi B, Emile JF, et al. KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res 2006;66:3992–5. 10.1158/0008-5472.CAN-06-0191 [PubMed: 16618717] [CrossRef]
15.
Khambata-Ford S, Garrett CR, Meropol NJ, Basik M, Harbison CT, Wu S, et al. Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab. J Clin Oncol 2007;25:3230–7. 10.1200/JCO.2006.10.5437 [PubMed: 17664471] [CrossRef]
16.
Adams RA, Meade AM, Seymour MT, Wilson RH, Madi A, Fisher D, et al. Intermittent versus continuous oxaliplatin and fluoropyrimidine combination chemotherapy for first-line treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet Oncol 2011;12:642–53. 10.1016/S1470-2045(11)70102-4 [PMC free article: PMC3159416] [PubMed: 21641867] [CrossRef]
17.
Richman SD, Adams R, Quirke P, Butler R, Hemmings G, Chambers P, et al. Pre-trial inter-laboratory analytical validation of the FOCUS4 personalised therapy trial. J Clin Pathol 2016;69:35–41. 10.1136/jclinpath-2015-203097 [PMC free article: PMC4717430] [PubMed: 26350752] [CrossRef]
18.
Smith CG, Fisher D, Claes B, Maughan TS, Idziaszczyk S, Peuteman G, et al. Somatic profiling of the epidermal growth factor receptor pathway in tumors from patients with advanced colorectal cancer treated with chemotherapy ± cetuximab. Clin Cancer Res 2013;19:4104–13. 10.1158/1078-0432.CCR-12-2581 [PMC free article: PMC3732482] [PubMed: 23741067] [CrossRef]
19.
Adkins D, Ley J, Worden F, Sacco AG, Palka K, Grilley-Olson JE, et al. Palbociclib and cetuximab in platinum-resistant and in cetuximab-resistant human papilomavirus-unrelated head and neck cancer: a multicentre, multigroup, phase 2 trial. Lancet Oncol 2019;20:1295–1305. 10.1016/S1470-2045(19)30405-X [PubMed: 31351869] [CrossRef]
20.
Brown LC, Graham J, Fisher D, Adams R, Seligmann J, Seymour M et al. Experiences of running a stratified medicine adaptive platform trial: challenges and lessons learned from 10 years of the FOCUS4 trial in metastatic colorectal cancer. Clin Trials 2022;19:146–57. 10.1177/17407745211069879 [PMC free article: PMC9036145] [PubMed: 35083924] [CrossRef]
21.
National Institute for Health and Care Research. NIHR Welcomes New Vision for the Future of UK Clinical Research Delivery. 2021. URL: www​.nihr.ac.uk/news/nihr-welcomes-new-vision-for-the-future-of-uk-clinical-research-delivery/27308 (accessed 23 March 2021).
22.
Sirinukunwattana K, Domingo E, Richman SD, Redmond KL, Blake A, Verrill C, et al. Image-based consensus molecular subtype (imCMS) classification of colorectal cancer using deep learning. Gut 2021;70:544–54. 10.1136/gutjnl-2019-319866 [PMC free article: PMC7873419] [PubMed: 32690604] [CrossRef]
23.
Middleton G, Fletcher P, Popat S, Savage J, Summers Y, Greystoke A, et al. The National Lung Matrix Trial of personalized therapy in lung cancer. Nature 2020;583:807–12. 10.1038/s41586-020-2481-8 [PMC free article: PMC7116732] [PubMed: 32669708] [CrossRef]
24.
Clinicaltrials.gov. Lung-MAP: Biomarker-targeted Second-line Therapy in Treating Patients With Recurrent Stage IV Squamous Cell Lung Cancer. URL: www​.clinicaltrials.gov​/ct2/show/NCT02154490 (accessed 9 September 2022).
25.
Flaherty KT, Gray R, Chen A, Li S, Patton D, Hamilton SR, et al. The Molecular Analysis for Therapy Choice (NCI-MATCH) trial: lessons for genomic trial design. J Natl Cancer Inst 2020;112:1021–9. 10.1093/jnci/djz245 [PMC free article: PMC7566320] [PubMed: 31922567] [CrossRef]
26.
Flaherty KT, Gray RJ, Chen AP, Li S, McShane LM, Patton D, et al. Molecular landscape and actionable alterations in a genomically guided cancer clinical trial: National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH). J Clin Oncol 2020;38:3883–94. 10.1200/JCO.19.03010 [PMC free article: PMC7676882] [PubMed: 33048619] [CrossRef]
27.
Seligmann J, Fisher DJ, Brown LC, Adams RA, Graham J, Quirke P, et al. Inhibition of WEE1 is effective in TP53 and RAS mutant metastatic colorectal cancer (mCRC): a randomised phase II trial (FOCUS4-C) comparing adavosertib (AZD1775) with active monitoring. J Clin Oncol 2021;39(33). 10.1200/JCO.21.01435 [PMC free article: PMC8601321] [PubMed: 34538072] [CrossRef]
28.
RECOVERY. Results. URL: https:​//recoverytrial.net/results (accessed 14 November 2022).
29.
ECOG-ACRIN Cancer Research Group. NCI-MATCH/EAY131 Findings and Publications. URL: https://ecog-acrin​.org​/nci-match-eay131-findings (accessed 10 September 2022).
30.
S:CORT. S-CORT Stratification in Colorectal Cancer. URL: https://www​.s-cort.org (accessed 16 November 2022).
31.
The Beatson Institute. ACRCelerate. URL: https://www​.beatson.gla​.ac.uk/ACRCelerate/acrcelerate.html (accessed 16 November 2022).
32.
Catalogue of Somatic Mutations in Cancer. COSMIC v96, released 31-May-22. URL: http://cancer​.sanger​.ac.uk/cancergenome/projects/cosmic/ (accessed 15 November 2022).
33.
Engelman JA. Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat Rev Cancer 2009;9:550–62. 10.1038/nrc2664 [PubMed: 19629070] [CrossRef]
34.
Zhao L, Vogt PK. Helical domain and kinase domain mutations in p110alpha of phosphatidylinositol 3-kinase induce gain of function by different mechanisms. Proc Natl Acad Sci U S A 2008;105:2652–7. 10.1073/pnas.0712169105 [PMC free article: PMC2268191] [PubMed: 18268322] [CrossRef]
35.
Liao X, Lochhead P, Nishihara R, Morikawa T, Kuchiba A, Yamauchi M, et al. Aspirin use, tumor PIK3CA mutation, and colorectal-cancer survival. N Engl J Med 2012;367:1596–606. 10.1056/NEJMoa1207756 [PMC free article: PMC3532946] [PubMed: 23094721] [CrossRef]
36.
Velho S, Oliveira C, Ferreira A, Ferreira AC, Suriano G, Schwartz S, et al. The prevalence of PIK3CA mutations in gastric and colon cancer. Eur J Cancer 2005;41:1649–54. 10.1016/j.ejca.2005.04.022 [PubMed: 15994075] [CrossRef]
37.
Day FL, Jorissen RN, Lipton L, Mouradov D, Sakthianandeswaren A, Christie M, et al. PIK3CA and PTEN gene and exon mutation-specific clinicopathologic and molecular associations in colorectal cancer. Clin Cancer Res 2013;19:3285–96. 10.1158/1078-0432.CCR-12-3614 [PubMed: 23633456] [CrossRef]
38.
Ogino S, Liao X, Imamura Y, Yamauchi M, McCleary NJ, Ng K, et al. Predictive and prognostic analysis of PIK3CA mutation in stage III colon cancer intergroup trial. J Natl Cancer Inst 2013;105:1789–98. 10.1093/jnci/djt298 [PMC free article: PMC3848984] [PubMed: 24231454] [CrossRef]
39.
Bardelli A, Siena S. Molecular mechanisms of resistance to cetuximab and panitumumab in colorectal cancer. J Clin Oncol 2010;28:1254–61. 10.1200/JCO.2009.24.6116 [PubMed: 20100961] [CrossRef]
40.
Karapetis CS, Jonker D, Daneshmand M, Hanson JE, O’Callaghan CJ, Marginean C, et al. PIK3CA, BRAF, and PTEN status and benefit from cetuximab in the treatment of advanced colorectal cancer – results from NCIC CTG/AGITG CO.17. Clin Cancer Res 2014;20:744–53. 10.1158/1078-0432.CCR-13-0606 [PubMed: 24218517] [CrossRef]
41.
Rodon J, Dienstmann R, Serra V, Tabernero J. Development of PI3K inhibitors: lessons learned from early clinical trials. Nat Rev Clin Oncol 2013;10:143–53. 10.1038/nrclinonc.2013.10 [PubMed: 23400000] [CrossRef]
42.
Mishra R, Patel H, Alanazi S, Kilroy MK, Garrett JT. PI3K inhibitors in cancer: clinical implications and adverse effects. Int J Mol Sci 2021;22:3464. 10.3390/ijms22073464 [PMC free article: PMC8037248] [PubMed: 33801659] [CrossRef]
43.
Giovannucci E, Rimm EB, Stampfer MJ, Colditz GA, Ascherio A, Willett WC. Aspirin use and the risk for colorectal cancer and adenoma in male health professionals. Ann Intern Med 1994;121:241–6. 10.7326/0003-4819-121-4-199408150-00001 [PubMed: 8037405] [CrossRef]
44.
Rothwell PM, Wilson M, Elwin CE, Norrving B, Algra A, Warlow CP, Meade TW. Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. Lancet 2010;376:1741–50. 10.1016/S0140-6736(10)61543-7 [PubMed: 20970847] [CrossRef]
45.
Sandler RS, Halabi S, Baron JA, Budinger S, Paskett E, Keresztes R, et al. A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer. N Engl J Med 2003;348:883–90. 10.1056/NEJMoa021633 [PubMed: 12621132] [CrossRef]
46.
Cole BF, Logan RF, Halabi S, Benamouzig R, Sandler RS, Grainge MJ, et al. Aspirin for the chemoprevention of colorectal adenomas: meta-analysis of the randomized trials. J Natl Cancer Inst 2009;101:256–66. 10.1093/jnci/djn485 [PMC free article: PMC5975663] [PubMed: 19211452] [CrossRef]
47.
Algra AM, Rothwell PM. Effects of regular aspirin on long-term cancer incidence and metastasis: a systematic comparison of evidence from observational studies versus randomised trials. Lancet Oncol 2012;13:518–27. 10.1016/S1470-2045(12)70112-2 [PubMed: 22440112] [CrossRef]
48.
Rothwell PM, Wilson M, Price JF, Belch JF, Meade TW, Mehta Z. Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials. Lancet 2012;379:1591–601. 10.1016/S0140-6736(12)60209-8 [PubMed: 22440947] [CrossRef]
49.
Thun MJ, Jacobs EJ, Patrono C. The role of aspirin in cancer prevention. Nat Rev Clin Oncol 2012;9:259–67. 10.1038/nrclinonc.2011.199 [PubMed: 22473097] [CrossRef]
50.
Gay LJ, Felding-Habermann B. Contribution of platelets to tumour metastasis. Nat Rev Cancer 2011;11:123–34. 10.1038/nrc3004 [PMC free article: PMC6894505] [PubMed: 21258396] [CrossRef]
51.
Köhne CH, Cunningham D, Di Costanzo F, Glimelius B, Blijham G, Aranda E, et al. Clinical determinants of survival in patients with 5-fluorouracil-based treatment for metastatic colorectal cancer: results of a multivariate analysis of 3825 patients. Ann Oncol 2002;13:308–17. 10.1093/annonc/mdf034 [PubMed: 11886010] [CrossRef]
52.
Karpatkin S, Pearlstein E, Ambrogio C, Coller BS. Role of adhesive proteins in platelet tumor interaction in vitro and metastasis formation in vivo. J Clin Invest 1988;81:1012–19. 10.1172/JCI113411 [PMC free article: PMC329625] [PubMed: 3280598] [CrossRef]
53.
Gasic GJ, Gasic TB, Stewart CC. Antimetastatic effects associated with platelet reduction. Proc Natl Acad Sci U S A 1968;61:46–52. 10.1073/pnas.61.1.46 [PMC free article: PMC285903] [PubMed: 5246932] [CrossRef]
54.
Pearlstein E, Ambrogio C, Karpatkin S. Effect of antiplatelet antibody on the development of pulmonary metastases following injection of CT26 colon adenocarcinoma, Lewis lung carcinoma, and B16 amelanotic melanoma tumor cells into mice. Cancer Res 1984;44:3884–7. [PubMed: 6744304]
55.
Kim MY, Oskarsson T, Acharyya S, Nguyen DX, Zhang XH, Norton L, Massagué J. Tumor self-seeding by circulating cancer cells. Cell 2009;139:1315–26. 10.1016/j.cell.2009.11.025 [PMC free article: PMC2810531] [PubMed: 20064377] [CrossRef]
56.
ClinicalTrials.gov. Aspirin for Dukes C and High Risk Dukes B Colorectal Cancers (ASCOLT). URL: https:​//clinicaltrials​.gov/ct2/show/NCT00565708?term​=NCT00565708​%26draw=2%26rank=1 (accessed 16 November 2022).
57.
ClinicalTrials.gov. Add-Aspirin: A Trial Assessing the Effects of Aspirin on Disease Recurrence and Survival After Primary Therapy in Common Non Metastatic Solid Tumours. URL: https:​//clinicaltrials​.gov/ct2/show/NCT02804815?term​=NCT02804815​%26draw=2%26rank=1 (accessed 16 November 2022).
58.
Domingo E, Church DN, Sieber O, Ramamoorthy R, Yanagisawa Y, Johnstone E, et al. Evaluation of PIK3CA mutation as a predictor of benefit from nonsteroidal anti-inflammatory drug therapy in colorectal cancer. J Clin Oncol 2013;31:4297–305. 10.1200/JCO.2013.50.0322 [PubMed: 24062397] [CrossRef]
59.
Murphy C, Turner N, Wong H-L, Sinnathamby M, Tie J, Lee B, et al. Examining the impact of regular aspirin use and PIK3CA mutations on survival in stage 2 colon cancer. Intern Med J 2017;47:88–98. 10.1111/imj.13312 [PubMed: 27800646] [CrossRef]
60.
Reimers MS, Bastiaannet E, Langley RE, van Eijk R, van Vlierberghe RL, Lemmens VE, et al. Expression of HLA class I antigen, aspirin use, and survival after a diagnosis of colon cancer. JAMA Intern Med 2014;174:732–9. 10.1001/jamainternmed.2014.511 [PubMed: 24687028] [CrossRef]
61.
Cuzick J, Otto F, Baron JA, Brown PH, Burn J, Greenwald P, et al. Aspirin and non-steroidal anti-inflammatory drugs for cancer prevention: an international consensus statement. Lancet Oncol 2009;10:501–7. 10.1016/S1470-2045(09)70035-X [PubMed: 19410194] [CrossRef]
62.
Baigent C, Blackwell L, Collins R, Emberson J, Godwin J, Peto R, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 2009;373:1849–60. 10.1016/S0140-6736(09)60503-1 [PMC free article: PMC2715005] [PubMed: 19482214] [CrossRef]
63.
Burn J, Gerdes AM, Macrae F, Mecklin JP, Moeslein G, Olschwang S, et al. Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial. Lancet 2011;378:2081–7. 10.1016/S0140-6736(11)61049-0 [PMC free article: PMC3243929] [PubMed: 22036019] [CrossRef]
64.
Bhatt DL, Scheiman J, Abraham NS, Antman EM, Chan FK, Furberg CD, et al. ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol 2008;52:1502–17. 10.1016/j.jacc.2008.08.002 [PubMed: 19017521] [CrossRef]
65.
Chan AT, Ogino S, Fuchs CS. Aspirin use and survival after diagnosis of colorectal cancer. JAMA 2009;302:649–58. 10.1001/jama.2009.1112 [PMC free article: PMC2848289] [PubMed: 19671906] [CrossRef]
66.
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011;144:646–74. 10.1016/j.cell.2011.02.013 [PubMed: 21376230] [CrossRef]
67.
Ciccia A, Elledge SJ. The DNA damage response: making it safe to play with knives. Mol Cell 2010;40:179–204. 10.1016/j.molcel.2010.09.019 [PMC free article: PMC2988877] [PubMed: 20965415] [CrossRef]
68.
Golan T, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, et al. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N Engl J Med 2019;381:317–27. 10.1056/NEJMoa1903387 [PMC free article: PMC6810605] [PubMed: 31157963] [CrossRef]
69.
Moore K, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med 2018;379:2495–505. 10.1056/NEJMoa1810858 [PubMed: 30345884] [CrossRef]
70.
Kaelin WG. The concept of synthetic lethality in the context of anticancer therapy. Nat Rev Cancer 2005;5:689–98. 10.1038/nrc1691 [PubMed: 16110319] [CrossRef]
71.
Beck H, Nähse-Kumpf V, Larsen MS, O’Hanlon KA, Patzke S, Holmberg C, et al. Cyclin-dependent kinase suppression by WEE1 kinase protects the genome through control of replication initiation and nucleotide consumption. Mol Cell Biol 2012;32:4226–36. 10.1128/MCB.00412-12 [PMC free article: PMC3457333] [PubMed: 22907750] [CrossRef]
72.
Aarts M, Sharpe R, Garcia-Murillas I, Gevensleben H, Hurd MS, Shumway SD, et al. Forced mitotic entry of S-phase cells as a therapeutic strategy induced by inhibition of WEE1. Cancer Discov 2012;2:524–39. 10.1158/2159-8290.CD-11-0320 [PubMed: 22628408] [CrossRef]
73.
Lheureux S, Cristea MC, Bruce JP, Garg S, Cabanero M, Mantia-Smaldone G, et al. Adavosertib plus gemcitabine for platinum-resistant or platinum-refractory recurrent ovarian cancer: a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet 2021;397:281–92. 10.1016/S0140-6736(20)32554-X [PubMed: 33485453] [CrossRef]
74.
Cuneo KC, Morgan MA, Sahai V, Schipper MJ, Parsels LA, Parsels JD, et al. Dose escalation trial of the Wee1 inhibitor adavosertib (AZD1775) in combination with gemcitabine and radiation for patients with locally advanced pancreatic cancer. J Clin Oncol 2019;37:2643–50. 10.1200/JCO.19.00730 [PMC free article: PMC7006846] [PubMed: 31398082] [CrossRef]
75.
Molinari M. Cell cycle checkpoints and their inactivation in human cancer. Cell Prolif 2000;33:261–74. 10.1046/j.1365-2184.2000.00191.x [PMC free article: PMC6496592] [PubMed: 11063129] [CrossRef]
76.
Kawabe T. G2 checkpoint abrogators as anticancer drugs. Mol Cancer Ther 2004;3:513–19. 10.1158/1535-7163.513.3.4 [PubMed: 15078995] [CrossRef]
77.
Rajeshkumar NV, De Oliveira E, Ottenhof N, Watters J, Brooks D, Demuth T, et al. MK-1775, a potent Wee1 inhibitor, synergizes with gemcitabine to achieve tumor regressions, selectively in p53-deficient pancreatic cancer xenografts. Clin Cancer Res 2011;17:2799–806. 10.1158/1078-0432.CCR-10-2580 [PMC free article: PMC3307341] [PubMed: 21389100] [CrossRef]
78.
Murcia L, Clemente-Ruiz M, Pierre-Elies P, Royou A, Milán M. Selective killing of RAS-malignant tissues by exploiting oncogene-induced DNA damage. Cell Rep 2019;28:119–31.e4. 10.1016/j.celrep.2019.06.004 [PubMed: 31269434] [CrossRef]
79.
Fikaris AJ, Lewis AE, Abulaiti A, Tsygankova OM, Meinkoth JL. Ras triggers ataxia-telangiectasia-mutated and Rad-3-related activation and apoptosis through sustained mitogenic signaling. J Biol Chem 2006;281:34759–67. 10.1074/jbc.M606737200 [PubMed: 16968694] [CrossRef]
80.
Weisberg E, Nonami A, Chen Z, Liu F, Zhang J, Sattler M, et al. Identification of Wee1 as a novel therapeutic target for mutant RAS-driven acute leukemia and other malignancies. Leukemia 2015;29:27–37. 10.1038/leu.2014.149 [PMC free article: PMC4667710] [PubMed: 24791855] [CrossRef]
81.
Do K, Wilsker D, Ji J, Zlott J, Freshwater T, Kinders RJ, et al. Phase I study of single-agent AZD1775 (MK-1775), a Wee1 kinase inhibitor, in patients with refractory solid tumors. J Clin Oncol 2015;33:3409–15. 10.1200/JCO.2014.60.4009 [PMC free article: PMC4606059] [PubMed: 25964244] [CrossRef]
82.
Seymour MT, Maughan TS, Ledermann JA, Topham C, James R, Gwyther SJ, et al. Different strategies of sequential and combination chemotherapy for patients with poor prognosis advanced colorectal cancer (MRC FOCUS): a randomised controlled trial. Lancet 2007;370:143–52. 10.1016/S0140-6736(07)61087-3 [PubMed: 17630037] [CrossRef]
83.
Malla SB, Fisher DJ, Domingo E, Blake A, Hassanieh S, Redmond KL, et al. In-depth clinical and biological exploration of DNA damage immune response as a biomarker for oxaliplatin use in colorectal cancer. Clin Cancer Res 2021;27:288–300. 10.1158/1078-0432.CCR-20-3237 [PMC free article: PMC7614625] [PubMed: 33028592] [CrossRef]
84.
Hong DS, Fakih MG, Strickler JH, Desai J, Durm GA, Shapiro GI, et al. KRASG12C inhibition with sotorasib in advanced solid tumors. N Engl J Med 2020;383:1207–17. 10.1056/NEJMoa1917239 [PMC free article: PMC7571518] [PubMed: 32955176] [CrossRef]
85.
Hobbs GA, Der CJ, Rossman KL. RAS isoforms and mutations in cancer at a glance. J Cell Sci 2016;129:1287–92. 10.1242/jcs.182873 [PMC free article: PMC4869631] [PubMed: 26985062] [CrossRef]
86.
de Bono J, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, et al. Olaparib for metastatic castration-resistant prostate cancer. N Engl J Med 2020;382:2091–102. 10.1056/NEJMoa1911440 [PubMed: 32343890] [CrossRef]
87.
Mauri G, Arena S, Siena S, Bardelli A, Sartore-Bianchi A. The DNA damage response pathway as a land of therapeutic opportunities for colorectal cancer. Ann Oncol 2020;31:1135–47. 10.1016/j.annonc.2020.05.027 [PubMed: 32512040] [CrossRef]
88.
Adams R, Brown E, Brown L, Butler R, Falk S, Fisher D, et al. Inhibition of EGFR, HER2, and HER3 signalling in patients with colorectal cancer wild-type for BRAF, PIK3CA, KRAS, and NRAS (FOCUS4-D): a phase 2–3 randomised trial. Lancet Gastroenterol Hepatol 2018;3:162–71. 10.1016/S2468-1253(17)30394-1 [PMC free article: PMC6125825] [PubMed: 29254887] [CrossRef]
89.
Kapitanović S, Radosević S, Slade N, Kapitanović M, Andelinović S, Ferencić Z, et al. Expression of erbB-3 protein in colorectal adenocarcinoma: correlation with poor survival. J Cancer Res Clin Oncol 2000;126:205–11. 10.1007/s004320050034 [PubMed: 10782893] [CrossRef]
90.
Baselga J, Swain SM. Novel anticancer targets: revisiting ERBB2 and discovering ERBB3. Nat Rev Cancer 2009;9:463–75. 10.1038/nrc2656 [PubMed: 19536107] [CrossRef]
91.
Scartozzi M, Mandolesi A, Giampieri R, Bittoni A, Pierantoni C, Zaniboni A, et al. The role of HER-3 expression in the prediction of clinical outcome for advanced colorectal cancer patients receiving irinotecan and cetuximab. Oncologist 2011;16:53–60. 10.1634/theoncologist.2010-0119 [PMC free article: PMC3228051] [PubMed: 21212430] [CrossRef]
92.
Wheeler DL, Huang S, Kruser TJ, Nechrebecki MM, Armstrong EA, Benavente S, et al. Mechanisms of acquired resistance to cetuximab: role of HER (ErbB) family members. Oncogene 2008;27:3944–56. 10.1038/onc.2008.19 [PMC free article: PMC2903615] [PubMed: 18297114] [CrossRef]
93.
Sergina NV, Rausch M, Wang D, Blair J, Hann B, Shokat KM, Moasser MM. Escape from HER-family tyrosine kinase inhibitor therapy by the kinase-inactive HER3. Nature 2007;445:437–41. 10.1038/nature05474 [PMC free article: PMC3025857] [PubMed: 17206155] [CrossRef]
94.
Seligmann JF, Hatch AJ, Richman SD, Elliott F, Jacobs B, Brown S, et al. Association of tumor HER3 messenger RNA expression with panitumumab efficacy in advanced colorectal cancer. JAMA Oncol 2018;4:564–8. 10.1001/jamaoncol.2017.3168 [PMC free article: PMC5933356] [PubMed: 29075780] [CrossRef]
95.
Richman SD, Southward K, Chambers P, Cross D, Barrett J, Hemmings G, et al. HER2 overexpression and amplification as a potential therapeutic target in colorectal cancer: analysis of 3256 patients enrolled in the QUASAR, FOCUS and PICCOLO colorectal cancer trials. J Pathol 2016;238:562–70. 10.1002/path.4679 [PMC free article: PMC4785607] [PubMed: 26690310] [CrossRef]
96.
Bertotti A, Migliardi G, Galimi F, Sassi F, Torti D, Isella C, et al. A molecularly annotated platform of patient-derived xenografts (‘xenopatients’) identifies HER2 as an effective therapeutic target in cetuximab-resistant colorectal cancer. Cancer Discov 2011;1:508–23. 10.1158/2159-8290.CD-11-0109 [PubMed: 22586653] [CrossRef]
97.
Hickinson DM, Klinowska T, Speake G, Vincent J, Trigwell C, Anderton J, et al. AZD8931, an equipotent, reversible inhibitor of signaling by epidermal growth factor receptor, ERBB2 (HER2), and ERBB3: a unique agent for simultaneous ERBB receptor blockade in cancer. Clin Cancer Res 2010;16:1159–69. 10.1158/1078-0432.CCR-09-2353 [PubMed: 20145185] [CrossRef]
98.
Seligmann JF, Fisher D, Smith CG, Richman SD, Elliott F, Brown S, et al. Investigating the poor outcomes of BRAF-mutant advanced colorectal cancer: analysis from 2530 patients in randomised clinical trials. Ann Oncol 2017;28:562–8. 10.1093/annonc/mdw645 [PubMed: 27993800] [CrossRef]
99.
Rowland A, Dias MM, Wiese MD, Kichenadasse G, McKinnon RA, Karapetis CS, Sorich MJ. Meta-analysis of BRAF mutation as a predictive biomarker of benefit from anti-EGFR monoclonal antibody therapy for RAS wild-type metastatic colorectal cancer. Br J Cancer 2015;112:1888–94. 10.1038/bjc.2015.173 [PMC free article: PMC4580381] [PubMed: 25989278] [CrossRef]
100.
Frattini M, Saletti P, Romagnani E, Martin V, Molinari F, Ghisletta M, et al. PTEN loss of expression predicts cetuximab efficacy in metastatic colorectal cancer patients. Br J Cancer 2007;97:1139–45. 10.1038/sj.bjc.6604009 [PMC free article: PMC2360431] [PubMed: 17940504] [CrossRef]
101.
Koopman M, Antonini NF, Douma J, Wals J, Honkoop AH, Erdkamp FL, et al. Sequential versus combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in advanced colorectal cancer (CAIRO): a phase III randomised controlled trial. Lancet 2007;370:135–42. 10.1016/S0140-6736(07)61086-1 [PubMed: 17630036] [CrossRef]
102.
Hegewisch-Becker S, Graeven U, Lerchenmüller CA, Killing B, Depenbusch R, Steffens CC, et al. Maintenance strategies after first-line oxaliplatin plus fluoropyrimidine plus bevacizumab for patients with metastatic colorectal cancer (AIO 0207): a randomised, non-inferiority, open-label, phase 3 trial. Lancet Oncol 2015;16:1355–69. 10.1016/S1470-2045(15)00042-X [PubMed: 26361971] [CrossRef]
103.
Good Clinical Practice Network. ICH harmonised guideline integrated addendum to ICH E6(R1): Guideline for Good Clinical Practice ICH E6(R2). URL: https://ichgcp​.net (accessed 16 November 2022).
104.
National Cancer Institute. Common Terminology Criteria for Adverse Events v3.0 (CTCAE). URL: https://ctep​.cancer.gov​/protocoldevelopment​/electronic_applications​/docs/ctcaev3.pdf (accessed 16 November 2022).
105.
Royston P, Parmar MK. Restricted mean survival time: an alternative to the hazard ratio for the design and analysis of randomized trials with a time-to-event outcome. BMC Med Res Methodol 2013;13:152. 10.1186/1471-2288-13-152 [PMC free article: PMC3922847] [PubMed: 24314264] [CrossRef]
106.
Barthel FMS RP, Parmar MKB. A menu-driven facility for sample-size calculation in novel multi-arm, multi-stage randomized controlled trials with a time-to-event outcome. Stata J 2009;9:505–23 10.1177/1536867X0900900401 [CrossRef]
107.
Austin PC. Variance estimation when using inverse probability of treatment weighting (IPTW) with survival analysis. Stat Med 2016;35:5642–55. 10.1002/sim.7084 [PMC free article: PMC5157758] [PubMed: 27549016] [CrossRef]
108.
Grambsch PM, Therneau TM. Proportional hazards tests and diagnostics based on weighted residuals. Biometrika 1994;81:515–26. 10.1093/biomet/81.3.515 [CrossRef]
109.
Johnston S, Basik M, Hegg R, Lausoontornsiri W, Grzeda L, Clemons M, et al. Inhibition of EGFR, HER2, and HER3 signaling with AZD8931 in combination with anastrozole as an anticancer approach: Phase II randomized study in women with endocrine-therapy-naïve advanced breast cancer. Breast Cancer Res Treat 2016;160:91–9. 10.1007/s10549-016-3979-5 [PubMed: 27654971] [CrossRef]
110.
Baselga J, Hegg R, Vidal Losad M, Vidaurre T, Lluch A, Petrakova K, et al. Abstract LB-146: a phase II randomized placebo-controlled study of AZD8931, an inhibitor of EGFR, HER2, and HER3 signaling, plus paclitaxel (P) vs P alone in patients (pts) with low HER2-expressing advanced breast cancer (BC) (THYME). Cancer Res 2013;73(Suppl. 8):LB-146.
111.
Adams R, Fisher DJ, Graham J, Seligmann JF, Seymour M, Kaplan R, et al. Capecitabine versus active monitoring in stable or responding metastatic colorectal cancer after 16 weeks of first-line therapy: results of the randomized FOCUS4-N trial. J Clin Oncol 2021;39:3693–704. 10.1200/JCO.21.01436 [PMC free article: PMC8601309] [PubMed: 34516759] [CrossRef]
112.
NCCN. NCCN Guidelines for Patients: Colon Cancer. URL: www2​.tri-kobe.org/nccn​/guideline/colorectal/english/colon​.pdf (accessed 31 January 2022).
113.
Van Cutsem E, Cervantes A, Adam R, Sobrero A, Van Krieken JH, Aderka D, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol 2016;27:1386–422. 10.1093/annonc/mdw235 [PubMed: 27380959] [CrossRef]
114.
Simkens LH, van Tinteren H, May A, ten Tije AJ, Creemers GJ, Loosveld OJ, et al. Maintenance treatment with capecitabine and bevacizumab in metastatic colorectal cancer (CAIRO3): a phase 3 randomised controlled trial of the Dutch Colorectal Cancer Group. Lancet 2015;385:1843–52. 10.1016/S0140-6736(14)62004-3 [PubMed: 25862517] [CrossRef]
115.
Sherman SK, Lange JJ, Dahdaleh FS, Rajeev R, Gamblin TC, Polite BN, Turaga KK. Cost-effectiveness of maintenance capecitabine and bevacizumab for metastatic colorectal cancer. JAMA Oncol 2019;5:236–42. 10.1001/jamaoncol.2018.5070 [PMC free article: PMC6440196] [PubMed: 30489611] [CrossRef]
116.
Sonbol MB, Mountjoy LJ, Firwana B, Liu AJ, Almader-Douglas D, Mody K, et al. The role of maintenance strategies in metastatic colorectal cancer: a systematic review and network meta-analysis of randomized clinical trials. JAMA Oncol 2020;6:e194489. 10.1001/jamaoncol.2019.4489 [PMC free article: PMC6990730] [PubMed: 31855256] [CrossRef]
117.
Adams R, Goey K, Chibaudel B, Koopman M, Punt C, Arnold D, et al. Treatment breaks in first line treatment of advanced colorectal cancer: an individual patient data meta-analysis. Cancer Treat Rev 2021;99:102226. 10.1016/j.ctrv.2021.102226 [PubMed: 34130171] [CrossRef]
118.
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228–47. 10.1016/j.ejca.2008.10.026 [PubMed: 19097774] [CrossRef]
119.
Hague D, Townsend S, Masters L, Rauchenberger M, Van Looy N, Diaz-Montana C, et al. Changing platforms without stopping the train: experiences of data management and data management systems when adapting platform protocols by adding and closing comparisons. Trials 2019;20:294. 10.1186/s13063-019-3322-7 [PMC free article: PMC6540437] [PubMed: 31138292] [CrossRef]
120.
Schiavone F, Bathia R, Letchemanan K, Masters L, Amos C, Bara A, et al. This is a platform alteration: a trial management perspective on the operational aspects of adaptive and platform and umbrella protocols. Trials 2019;20:264. 10.1186/s13063-019-3216-8 [PMC free article: PMC6540525] [PubMed: 31138317] [CrossRef]
121.
Morrell L, Hordern J, Brown L, Sydes MR, Amos CL, Kaplan RS, et al. Mind the gap? The platform trial as a working environment. Trials 2019;20:297. 10.1186/s13063-019-3377-5 [PMC free article: PMC6540560] [PubMed: 31138284] [CrossRef]
122.
Antoniou M, Kolamunnage-Dona R, Wason J, Bathia R, Billingham C, Bliss JM, et al. Biomarker-guided trials: challenges in practice. Contemp Clin Trials Commun 2019;16:100493. 10.1016/j.conctc.2019.100493 [PMC free article: PMC6879976] [PubMed: 31788574] [CrossRef]
123.
Maughan TS, Meade AM, Adams RA, Richman SD, Butler R, Fisher D, et al. A feasibility study testing four hypotheses with phase II outcomes in advanced colorectal cancer (MRC FOCUS3): a model for randomised controlled trials in the era of personalised medicine? Br J Cancer 2014;110:2178–86. 10.1038/bjc.2014.182 [PMC free article: PMC4007241] [PubMed: 24743706] [CrossRef]
124.
Guinney J, Dienstmann R, Wang X, de Reyniès A, Schlicker A, Soneson C, et al. The consensus molecular subtypes of colorectal cancer. Nat Med 2015;21:1350–6. 10.1038/nm.3967 [PMC free article: PMC4636487] [PubMed: 26457759] [CrossRef]
125.
Feiler T, Gaitskell K, Maughan T, Hordern J. Personalised medicine: the promise, the hype and the pitfalls. New Bioeth 2017;23:1–12. 10.1080/20502877.2017.1314895 [PubMed: 28517985] [CrossRef]
126.
Hordern J, Maughan T, Feiler T, Morrell L, Horne R, Sullivan R. The ‘molecularly unstratified’ patient: a focus for moral, psycho-social and societal research. Biomed Hub 2017;2(suppl 1):146–53. 10.1159/000480422 [PMC free article: PMC6314434] [PubMed: 30613576] [CrossRef]
Copyright © 2022 Brown et al. This work was produced by Brown et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This is an Open Access publication distributed under the terms of the Creative Commons Attribution CC BY 4.0 licence, which permits unrestricted use, distribution, reproduction and adaption in any medium and for any purpose provided that it is properly attributed. See: https://creativecommons.org/licenses/by/4.0/. For attribution the title, original author(s), the publication source – Journals Library, and the DOI of the publication must be cited.
Bookshelf ID: NBK587973

Views

  • PubReader
  • Print View
  • Cite this Page
  • PDF version of this title (1.9M)

Other titles in this collection

Related information

  • PMC
    PubMed Central citations
  • PubMed
    Links to PubMed

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...