Review

Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA

Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA

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Kenna R Mills Shaw

*Author for correspondence:

E-mail Address: krshaw@mdanderson.org

Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA

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Published Online:24 Oct 2017https://doi.org/10.2217/pgs-2017-0094

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Abstract

Precision oncology is not an illusion, nor is it the magic bullet that will eradicate all cancers. Precision oncology is simply another weapon in our growing armament against cancer. Rather than honing in on the failures of a relatively young field, one should advocate for integrating its successes into widespread clinical practice, especially for indications, such as: ABL, ALK, BRAF, BRCA1, BRCA2, EGFR, KIT, KRAS, PDGFRA, PDGFRB, ROS1, BCR-ABL, FLT3 and ROS1, where aberrations have been shown to alter responses to US FDA approved drugs – that is, level 1 data. Moreover, to truly assess the promise of precision oncology, we must first begin by defining our expectations for this field. Importantly, we must recognize that the conception of precision oncology arose as an antithesis of the ‘one-size fits all’ cancer therapeutics approach. Consequently, tools used for evaluating these conventional, large-scale trials, are not directly transferable for assessing nonconventional, smaller-scale trials needed for evaluating precision oncology. Hence, a thorough vetting of precision oncology as another tool of the trade, must first begin by reassessing our expectations for this field, as well as current clinical trial designs and end point measurements. Importantly, we must recognize that most targeted therapy approaches are in their infancy, with only monotherapy approaches being assessed and combination therapies likely being necessary to fulfill the promise of precision oncology.

Keywords:

References

1 Prasad V. Perspective: the precision-oncology illusion. Nature 537(7619), S63 (2016).
Medline CASGoogle Scholar
2 Tannock IF, Hickman JA. Limits to personalized cancer medicine. N. Engl. J. Med. 375(13), 1289–1294 (2016).
MedlineGoogle Scholar
3 Le Tourneau C, Delord JP, Gonçalves A et al. Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): a multicentre, open-label, proof-of-concept, randomised, controlled Phase 2 trial. Lancet Oncol. 16(13), 1324–1334 (2015).
Medline CASGoogle Scholar
4 Schilsky R, Davies W. Highlights from the 2016 WIN Symposium, 27–29 June 2016, Paris: personalised therapy beyond next-generation sequencing. Ecancermedicalscience 10, 669 (2016).
MedlineGoogle Scholar
5 Tsimberidou AM, Kurzrock R. Precision medicine: lessons learned from the SHIVA trial. Lancet Oncol. 16(16), e579–e580 (2015).
MedlineGoogle Scholar
6 Berry DA. The brave new world of clinical cancer research: adaptive biomarker-driven trials integrating clinical practice with clinical research. Mol. Oncol. 9(5), 951–959 (2015).
MedlineGoogle Scholar
7 Renfro LA, Mallick H, An MW, Sargent DJ, Mandrekar SJ. Clinical trial designs incorporating predictive biomarkers. Cancer Treat. Rev. 43, 74–82 (2016).
Medline CASGoogle Scholar
8 Simon R, Maitournam A. Evaluating the efficiency of targeted designs for randomized clinical trials. Clin. Cancer. Res. 10(20), 6759–6763 (2004).
Medline CASGoogle Scholar
9 Pegram MD, Lipton A, Hayes DF et al. Phase II study of receptor-enhanced chemosensitivity using recombinant humanized anti-p185HER2/neu monoclonal antibody plus cisplatin in patients with HER2/neu-overexpressing metastatic breast cancer refractory to chemotherapy treatment. J. Clin. Oncol. 16(8), 2659–2671 (1998).
Medline CASGoogle Scholar
10 O'Brien SG, Guilhot F, Larson RA et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N. Engl. J. Med. 348(11), 994–1004 (2003).
MedlineGoogle Scholar
11 Druker BJ, Talpaz M, Resta DJ et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N. Engl. J. Med. 344(14), 1031–1037 (2001).
Medline CASGoogle Scholar
12 Ottmann OG, Druker BJ, Sawyers CL et al. A Phase 2 study of imatinib in patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoid leukemias. Blood 100(6), 1965–1971 (2002).
Medline CASGoogle Scholar
13 Druker BJ, Sawyers CL, Kantarjian H et al. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N. Engl. J. Med. 344(14), 1038–1042 (2001).
Medline CASGoogle Scholar
14 Shaw AT, Yeap BY, Mino-Kenudson M et al. Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK. J. Clin. Oncol. 27(26), 4247–4253 (2009).
Medline CASGoogle Scholar
15 Soda M, Choi YL, Enomoto M et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 448(7153), 561–566 (2007).
Medline CASGoogle Scholar
16 Won JK, Keam B, Koh J et al. Concomitant ALK translocation and EGFR mutation in lung cancer: a comparison of direct sequencing and sensitive assays and the impact on responsiveness to tyrosine kinase inhibitor. Ann. Oncol. 26(2), 348–354 (2015).
Medline CASGoogle Scholar
17 Bergethon K, Shaw AT, Ou SH et al. ROS1 rearrangements define a unique molecular class of lung cancers. J. Clin. Oncol. 30(8), 863–870 (2012).
Medline CASGoogle Scholar
18 Shaw AT, Ou SH, Bang YJ et al. Crizotinib in ROS1-rearranged non-small-cell lung cancer. N. Engl. J. Med. 371(21), 1963–1971 (2014).
MedlineGoogle Scholar
19 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. 11(2), 121–128 (2010).
Medline CASGoogle Scholar
20 Maemondo M, Inoue A, Kobayashi K et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N. Engl. J. Med. 362(25), 2380–2388 (2010).
Medline CASGoogle Scholar
21 Fukuoka M, Wu YL, Thongprasert S et al. Biomarker analyses and final overall survival results from a Phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). J. Clin. Oncol. 29(21), 2866–2874 (2011).
Medline CASGoogle Scholar
22 Yang JC, Wu YL, 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. 16(2), 141–151 (2015).
Medline CASGoogle Scholar
23 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. 13(3), 239–246 (2012).
Medline CASGoogle Scholar
24 Janne PA, Yang JC, Kim DW et al. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. N. Engl. J. Med. 372(18), 1689–1699 (2015).
MedlineGoogle Scholar
25 Chapman PB, Hauschild A, Robert C et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N. Engl. J. Med. 364(26), 2507–2516 (2011).
Medline CASGoogle Scholar
26 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. 33(34), 4032–4038 (2015).
Medline CASGoogle Scholar
27 Berry DA, Herbst RS, Rubin EH. Reports from the 2010 Clinical and Translational Cancer Research Think Tank meeting: design strategies for personalized therapy trials. Clin. Cancer. Res. 18(3), 638–644 (2012).
MedlineGoogle Scholar
28 Govindan R, Mandrekar SJ, Gerber DE et al. ALCHEMIST trials: a golden opportunity to transform outcomes in early-stage non-small cell lung cancer. Clin. Cancer. Res. 21(24), 5439–5444 (2015).
Medline CASGoogle Scholar
29 Gerber DE, Oxnard GR, Govindan R. ALCHEMIST: bringing genomic discovery and targeted therapies to early-stage lung cancer. Clin. Pharmacol. Ther. 97(5), 447–450 (2015).
Medline CASGoogle Scholar
30 Printz C. BATTLE to personalize lung cancer treatment. Novel clinical trial design and tissue gathering procedures drive biomarker discovery. Cancer 116(14), 3307–3308 (2010).
MedlineGoogle Scholar
31 Coyne GO, Takebe N, Chen AP. Defining precision: the precision medicine initiative trials NCI-MPACT and NCI-MATCH. Curr. Probl. Cancer doi:10.1016/j.currproblcancer.2017.02.001 (2017) (Epub ahead of print).
MedlineGoogle Scholar
32 Kaplan R. The FOCUS4 design for biomarker stratified trials. Chin. Clin. Oncol. 4(3), 35 (2015).
MedlineGoogle Scholar
33 Steue CE, Papadimitrakopoulou V, Herbst RS et al. Innovative clinical trials: The LUNG-MAP Study. Clin. Pharmacol. Ther. 97(5), 488–491 (2015).
MedlineGoogle Scholar
34 Printz C. I-SPY2 trial yields first results on combination therapy for triple-negative breast cancer. Cancer 120(6), 773 (2014).
MedlineGoogle Scholar
35 Kim C, Giaccone G. Lessons learned from BATTLE-2 in the war on cancer: the use of Bayesian method in clinical trial design. Ann. Transl. Med. 4(23), 466 (2016).
MedlineGoogle Scholar
36 Herbst RS, Gandara DR, Hirsch FR et al. Lung Master Protocol (Lung-MAP) – a biomarker-driven protocol for accelerating development of therapies for squamous cell lung cancer: SWOG S1400. Clin. Cancer. Res. 21(7), 1514–1524 (2015).
Medline CASGoogle Scholar
37 American Association for Cancer Research. NCI launches ALCHEMIST. Cancer Discov. 4(11), OF9 (2014).
Google Scholar
38 McNeil C. NCI-MATCH launch highlights new trial design in precision-medicine era. J. Natl Cancer Inst. 107(7), pii:djv193 (2015).
Google Scholar
39 Brower V. NCI-MATCH pairs tumor mutations with matching drugs. Nat. Biotechnol. 33(8), 790–791 (2015).
Medline CASGoogle Scholar
40 Colwell J. NCI-MATCH trial draws strong interest. Cancer Discov. 6(4), 334 (2016).
MedlineGoogle Scholar
41 Do K, O'Sullivan Coyne G, Chen AP. An overview of the NCI precision medicine trials-NCI MATCH and MPACT. Chin. Clin. Oncol. 4(3), 31 (2015).
MedlineGoogle Scholar
42 No authors listed. Trial watch: adaptive BATTLE trial uses biomarkers to guide lung cancer treatment. Nat. Rev. Drug Discov. 9(6), 423 (2010).
MedlineGoogle Scholar
43 Bross PF, Cohen MH, Williams GA, Pazdur R. FDA drug approval summaries: fulvestrant. Oncologist 7(6), 477–480 (2002).
Medline CASGoogle Scholar
44 Bundred N. Preclinical and clinical experience with fulvestrant (Faslodex) in postmenopausal women with hormone receptor-positive advanced breast cancer. Cancer Invest. 23(2), 173–181 (2005).
Medline CASGoogle Scholar
45 Buzdar AU. Fulvestrant – a novel estrogen receptor antagonist for the treatment of advanced breast cancer. Drugs Today (Barc.) 44(9), 679–692 (2008).
Medline CASGoogle Scholar
46 Chia S, Gradishar W. Fulvestrant: expanding the endocrine treatment options for patients with hormone receptor-positive advanced breast cancer. Breast 17(Suppl. 3), S16–S21 (2008).
MedlineGoogle Scholar
47 Dodwell D, Vergote I. A comparison of fulvestrant and the third-generation aromatase inhibitors in the second-line treatment of postmenopausal women with advanced breast cancer. Cancer Treat. Rev. 31(4), 274–282 (2005).
Medline CASGoogle Scholar
48 Gradishar W. Fulvestrant in the treatment of postmenopausal women with advanced breast cancer. Expert Rev. Anticancer Ther. 5(3), 445–453 (2005).
Medline CASGoogle Scholar
49 Howell A. Fulvestrant (‘Faslodex’): current and future role in breast cancer management. Crit. Rev. Oncol. Hematol. 57(3), 265–273 (2006).
MedlineGoogle Scholar
50 Howell A, Sapunar F. Fulvestrant revisited: efficacy and safety of the 500-mg dose. Clin. Breast Cancer 11(4), 204–210 (2011).
Medline CASGoogle Scholar
51 Morris C, Wakeling A. Fulvestrant (‘Faslodex’) – a new treatment option for patients progressing on prior endocrine therapy. Endocr. Relat. Cancer 9(4), 267–276 (2002).
Medline CASGoogle Scholar
52 Robertson JF, Erikstein B, Osborne KC et al. Pharmacokinetic profile of intramuscular fulvestrant in advanced breast cancer. Clin. Pharmacokinet. 43(8), 529–538 (2004).
Medline CASGoogle Scholar
53 Scott SM, Brown M, Come SE. Emerging data on the efficacy and safety of fulvestrant, a unique antiestrogen therapy for advanced breast cancer. Expert Opin. Drug Saf. 10(5), 819–826 (2011).
Medline CASGoogle Scholar
54 Xu B, Jiang Z, Shao Z et al. Fulvestrant 250 mg versus anastrozole for Chinese patients with advanced breast cancer: results of a multicentre, double-blind, randomised Phase III trial. Cancer Chemother. Pharmacol. 67(1), 223–230 (2011).
Medline CASGoogle Scholar
55 Baselga J, Bradbury I, Eidtmann H et al. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, Phase 3 trial. Lancet 379(9816), 633–640 (2012).
Medline CASGoogle Scholar
56 Sterns EE. Changing emphasis in breast diagnosis: the surgeon's role in evaluating mammographic abnormalities. J. Am. Coll. Surg. 184(3), 297–302 (1997).
Medline CASGoogle Scholar
57 Rusnak DW, Lackey K, Affleck K et al. The effects of the novel, reversible epidermal growth factor receptor/ErbB-2 tyrosine kinase inhibitor, GW2016, on the growth of human normal and tumor-derived cell lines in vitro and in vivo. Mol. Cancer Ther. 1(2), 85–94 (2001).
Medline CASGoogle Scholar
58 Geyer CE, Forster J, Lindquist D et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N. Engl. J. Med. 355(26), 2733–2743 (2006).
Medline CASGoogle Scholar
59 Bilancia D, Rosati G, Dinota A, Germano D, Romano R, Manzione L. Lapatinib in breast cancer. Ann. Oncol. (Suppl. 6), vi26–vi30 (2007).
MedlineGoogle Scholar
60 Konecny GE, Pegram MD, Venkatesan N et al. Activity of the dual kinase inhibitor lapatinib (GW572016) against HER-2-overexpressing and trastuzumab-treated breast cancer cells. Cancer Res. 66(3), 1630–1639 (2006).
Medline CASGoogle Scholar
61 Amiri-Kordestani L, Blumenthal GM, Xu QC et al. FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin. Cancer Res. 20(17), 4436–4441 (2014).
Medline CASGoogle Scholar
62 Traynor K. Ado-trastuzumab emtansine approved for advanced breast cancer. Am. J. Health. Syst. Pharm. 70(7), 56 (2013).
Google Scholar
63 Romond EH, Perez EA, Bryant J et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N. Engl. J. Med. 353(16), 1673–1684 (2005).
Medline CASGoogle Scholar
64 Shitara K, Yonesaka K, Denda T et al. Randomized study of FOLFIRI plus either panitumumab or bevacizumab for wild-type KRAS colorectal cancer-WJOG 6210G. Cancer Sci. 107(12), 1843–1850 (2016).
Medline CASGoogle Scholar
65 Peeters M, Oliner KS, Price TJ et al. Analysis of KRAS/NRAS mutations in a Phase III study of panitumumab with FOLFIRI compared with FOLFIRI alone as second-line treatment for metastatic colorectal cancer. Clin. Cancer Res. 21(24), 5469–5479 (2015).
Medline CASGoogle Scholar
66 Baas JM, Krens LL, Bos MM et al. Safety and efficacy of the addition of simvastatin to panitumumab in previously treated KRAS mutant metastatic colorectal cancer patients. Anticancer Drugs 26(8), 872–877 (2015).
Medline CASGoogle Scholar
67 No author listed. New treatments for colorectal cancer. FDA Consum. 38(3), 17 (2004).
Google Scholar
68 Lieberman R. Food and Drug Administration approval of cetuximab and a new KRAS genetic test for metastatic colorectal cancer: major advance but just the tip of the biomarker iceberg. Am. J. Ther. 19(6), 395–396 (2012).
MedlineGoogle Scholar
69 Goldberg RM. Cetuximab. Nat. Rev. Drug Discov. (Suppl.), S1–S10 (2005).
Google Scholar
70 Garrett CR, Eng C. Cetuximab in the treatment of patients with colorectal cancer. Expert Opin. Biol. Ther. 11(7), 937–949 (2011).
Medline CASGoogle Scholar
71 Van Cutsem E, Köhne CH, Hitre E et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N. Engl. J. Med. 360(14), 1408–1417 (2009).
Medline CASGoogle Scholar
72 Cunningham D, Humblet Y, Siena S et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N. Engl. J. Med. 351(4), 337–345 (2004).
Medline CASGoogle Scholar
73 Cohen MH, Chen H, Shord S et al. Approval summary: cetuximab in combination with cisplatin or carboplatin and 5-fluorouracil for the first-line treatment of patients with recurrent locoregional or metastatic squamous cell head and neck cancer. Oncologist 18(4), 460–466 (2013).
Medline CASGoogle Scholar
74 No author listed. Treatment for head and neck cancer. FDA Consum. 40(3), 7 (2006).
Google Scholar
75 No author listed. Cetuximab approved by FDA for treatment of head and neck squamous cell cancer. Cancer Biol. Ther. 5(4), 340–342 (2006).
MedlineGoogle Scholar
76 Kim DW, Mehra R, Tan DS et al. Activity and safety of ceritinib in patients with ALK-rearranged non-small-cell lung cancer (ASCEND-1): updated results from the multicentre, open-label, Phase 1 trial. Lancet Oncol. 17(4), 452–463 (2016).
Medline CASGoogle Scholar
77 Khozin S, Blumenthal GM, Zhang L et al. FDA approval: ceritinib for the treatment of metastatic anaplastic lymphoma kinase-positive non-small cell lung cancer. Clin. Cancer Res. 21(11), 2436–2439 (2015).
Medline CASGoogle Scholar
78 Shaw AT, Engelman JA. Ceritinib in ALK-rearranged non-small-cell lung cancer. N. Engl. J. Med. 370(13), 1189–1197 (2014).
Medline CASGoogle Scholar
79 Shaw AT, Engelman JA. Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: a single-group, multicentre, Phase 2 trial. Lancet Oncol. 17(2), 234–242 (2016).
Medline CASGoogle Scholar
80 Sakamoto H, Tsukaguchi T, Hiroshima S et al. CH5424802, a selective ALK inhibitor capable of blocking the resistant gatekeeper mutant. Cancer Cell 19(5), 679–690 (2011).
Medline CASGoogle Scholar
81 Larkins E, Blumenthal GM, Chen H. FDA approval: alectinib for the treatment of metastatic, ALK-positive non-small cell lung cancer following crizotinib. Clin. Cancer Res. 22(21), 5171–5176 (2016).
Medline CASGoogle Scholar
82 Song Z, Wang M, Zhang A. Alectinib: a novel second generation anaplastic lymphoma kinase (ALK) inhibitor for overcoming clinically-acquired resistance. Acta Pharm. Sin. B5(1), 34–37 (2015).
Google Scholar
83 Shaw AT, Kim DW, Nakagawa K et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N. Engl. J. Med. 368(25), 2385–2394 (2013).
Medline CASGoogle Scholar
84 Malik SM, Maher VE, Bijwaard KE et al. U.S. Food and Drug Administration approval: crizotinib for treatment of advanced or metastatic non-small cell lung cancer that is anaplastic lymphoma kinase positive. Clin. Cancer Res. 20(8), 2029–2034 (2014).
Medline CASGoogle Scholar
85 Kazandjian D, Blumenthal GM, Chen HY et al. FDA approval summary: crizotinib for the treatment of metastatic non-small cell lung cancer with anaplastic lymphoma kinase rearrangements. Oncologist 19(10), e5–e11 (2014).
MedlineGoogle Scholar
86 Perez-Soler R. Phase II clinical trial data with the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib (OSI-774) in non-small-cell lung cancer. Clin. Lung Cancer 6(Suppl. 1), S20–S3 (2004).
Medline CASGoogle Scholar
87 Sequist LV, Yang JC, 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. 31(27), 3327–3334 (2013).
Medline CASGoogle Scholar
88 Li D, Ambrogio L, Shimamura T et al. BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene 27(34), 4702–4711 (2008).
Medline CASGoogle Scholar
89 Metro G, Crino L. The LUX-Lung clinical trial program of afatinib for non-small-cell lung cancer. Expert Rev. Anticancer Ther. 11(5), 673–682 (2011).
Medline CASGoogle Scholar
90 Yang JC, Shih JY, Su WC et al. Afatinib for patients with lung adenocarcinoma and epidermal growth factor receptor mutations (LUX-Lung 2): a Phase 2 trial. Lancet Oncol. 13(5), 539–548 (2012).
Medline CASGoogle Scholar
91 Miller VA, Hirsh V, Cadranel J et al. Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a Phase 2b/3 randomised trial. Lancet Oncol. 13(5), 528–538 (2012).
Medline CASGoogle Scholar
92 Li KL, Li L, Zhang P et al. A multicenter double-blind Phase II study of metformin with gefitinib as first-line therapy of locally advanced non-small-cell lung cancer. Clin. Lung Cancer 18(3), 340–343 (2017).
Medline CASGoogle Scholar
93 Kim HR, Jang JS, Sun JM et al. A randomized, Phase II study of gefitinib alone versus nimotuzumab plus gefitinib after platinum-based chemotherapy in advanced non-small cell lung cancer (KCSG LU12–01). Oncotarget 8(9), 15943–15951 (2017).
MedlineGoogle Scholar
94 Levy A, Bardet E, Lacas B et al. A Phase II open-label multicenter study of gefitinib in combination with irradiation followed by chemotherapy in patients with inoperable stage III non-small cell lung cancer. Oncotarget 8(9), 15924–15933 (2017).
MedlineGoogle Scholar
95 Hsiue EH, Lee JH, Lin CC et al. Profile of the therascreen(R) EGFR RGQ PCR kit as a companion diagnostic for gefitinib in non-small cell lung cancer. Expert Rev. Mol. Diagn. 16(12), 1251–1257 (2016).
Medline CASGoogle Scholar
96 Cappuzzo F, Morabito A, Normanno N et al. Efficacy and safety of rechallenge treatment with gefitinib in patients with advanced non-small cell lung cancer. Lung Cancer 99, 31–37 (2016).
MedlineGoogle Scholar
97 Syed YY. Therascreen(R) EGFR RGQ PCR Kit: a companion diagnostic for afatinib and gefitinib in non-small cell lung cancer. Mol. Diagn. Ther. 20(2), 191–198 (2016).
Medline CASGoogle Scholar
98 Domblides C, Antoine M, Lavole A et al. [Crizotinib for ROS1-rearranged non-small cell lung cancer patients]. Bull. Cancer 104(4), 303–310 (2017).
MedlineGoogle Scholar
99 Zhang L, Jiang T, Zhao C et al. Efficacy of crizotinib and pemetrexed-based chemotherapy in Chinese NSCLC patients with ROS1 rearrangement. Oncotarget 7(46), 75145–75154 (2016).
MedlineGoogle Scholar
100 Shaw AT, Solomon BJ. Crizotinib in ROS1-rearranged non-small-cell lung cancer. N. Engl. J. Med. 371(21), 1963–1971 (2014).
MedlineGoogle Scholar
101 Sholl LM, Sun H, Butaney M et al. ROS1 immunohistochemistry for detection of ROS1-rearranged lung adenocarcinomas. Am. J. Surg. Pathol. 37(9), 1441–1449 (2013).
MedlineGoogle Scholar
102 Kaufman B, Shapira-Frommer R, Schmutzler RK et al. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J. Clin. Oncol. 33(3), 244–250 (2015).
Medline CASGoogle Scholar
103 Kim G, Ison G, McKee AE et al. FDA approval summary: olaparib monotherapy in patients with deleterious germline BRCA-mutated advanced ovarian cancer treated with three or more lines of chemotherapy. Clin. Cancer Res. 21(19), 4257–4261 (2015).
Medline CASGoogle Scholar
104 Crafton SM, Bixel K, Hays JL. PARP inhibition and gynecologic malignancies: a review of current literature and on-going trials. Gynecol. Oncol. 142(3), 588–596 (2016).
Medline CASGoogle Scholar
105 Tewari KS, Eskander RN, Monk BJ. Development of olaparib for BRCA-deficient recurrent epithelial ovarian cancer. Clin. Cancer Res. 21(17), 3829–3835 (2015).
Medline CASGoogle Scholar
106 Rafii S, Gourley C, Kumar R et al. Baseline clinical predictors of antitumor response to the PARP inhibitor olaparib in germline BRCA1/2 mutated patients with advanced ovarian cancer. Oncotarget 8(29), 47154–47160 (2017).
MedlineGoogle Scholar
107 Thomas HD, Calabrese CR, Batey MA et al. Preclinical selection of a novel poly(ADP-ribose) polymerase inhibitor for clinical trial. Mol. Cancer Ther. 6(3), 945–956 (2007).
Medline CASGoogle Scholar
108 Liu JF, Konstantinopoulos PA, Matulonis UA. PARP inhibitors in ovarian cancer: current status and future promise. Gynecol. Oncol. 133(2), 362–369 (2014).
Medline CASGoogle Scholar
109 No authors listed. Rucaparib approved for ovarian cancer. Cancer Discov. 7(2), 120–121 (2017).
Google Scholar
110 Ravnan MC, Matalka MS. Vemurafenib in patients with BRAF V600E mutation-positive advanced melanoma. Clin. Ther. 34(7), 1474–1486 (2012).
Medline CASGoogle Scholar
111 Heakal Y, Kester M, Savage S. Vemurafenib (PLX4032): an orally available inhibitor of mutated BRAF for the treatment of metastatic melanoma. Ann. Pharmacother. 45(11), 1399–1405 (2011).
Medline CASGoogle Scholar
112 Lopez-Rios F, Angulo B, Gomez B et al. Comparison of testing methods for the detection of BRAF V600E mutations in malignant melanoma: pre-approval validation study of the companion diagnostic test for vemurafenib. PLoS ONE 8(1), e53733 (2013).
Medline CASGoogle Scholar
113 Liszkay G. [Vemurafenib (Zelboraf) in the therapy of melanoma]. Magy. Onkol. 57(2), 110–113 (2013).
MedlineGoogle Scholar
114 Flaherty L, Hamid O, Linette G et al. A single-arm, open-label, expanded access study of vemurafenib in patients with metastatic melanoma in the United States. Cancer J. 20(1), 18–24 (2014).
Medline CASGoogle Scholar
115 Thompson CA. New melanoma drug requires gene mutation test. Am. J. Health Syst. Pharm. 68(19), 1764 (2011).
MedlineGoogle Scholar
116 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 379(9829), 1893–1901 (2012).
Medline CASGoogle Scholar
117 Hauschild A, Grob JJ, Demidov LV et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, Phase 3 randomised controlled trial. Lancet 380(9839), 358–365 (2012).
Medline CASGoogle Scholar
118 Long GV, Trefzer U, Davies MA et al. Dabrafenib in patients with Val600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain (BREAK-MB): a multicentre, open-label, Phase 2 trial. Lancet Oncol. 13(11), 1087–1095; 84 (2012).
Medline CASGoogle Scholar
119 Ascierto PA, Minor D, Ribas A et al. Phase II trial (BREAK-2) of the BRAF inhibitor dabrafenib (GSK2118436) in patients with metastatic melanoma. J Clin. Oncol. 31(26), 3205–3211; 85 (2013).
Medline CASGoogle Scholar
120 McGettigan S. Dabrafenib: a new therapy for use in BRAF-mutated metastatic melanoma. J. Adv. Pract. Oncol. 5(3), 211–215 (2014).
MedlineGoogle Scholar
121 Johnson DB, Flaherty KT, Weber JS et al. Combined BRAF (Dabrafenib) and MEK inhibition (Trametinib) in patients with BRAFV600-mutant melanoma experiencing progression with single-agent BRAF inhibitor. J. Clin. Oncol. 32(33), 3697–3704 (2014).
Medline CASGoogle Scholar
122 Long GV, Stroyakovskiy D, Gogas H et al. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N. Engl. J. Med. 371(20), 1877–1888 (2014).
Medline CASGoogle Scholar
123 Grob JJ, Amonkar MM, Karaszewska B et al. Comparison of dabrafenib and trametinib combination therapy with vemurafenib monotherapy on health-related quality of life in patients with unresectable or metastatic cutaneous BRAF Val600-mutation-positive melanoma (COMBI-v): results of a Phase 3, open-label, randomised trial. Lancet Oncol. 16(13), 1389–1398 (2015).
Medline CASGoogle Scholar
124 Long GV, Stroyakovskiy D, Gogas H et al. Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAF-mutant melanoma: a multicentre, double-blind, Phase 3 randomised controlled trial. Lancet 386(9992), 444–451 (2015).
Medline CASGoogle Scholar
125 Robert C, Karaszewska B, Schachter J et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N. Engl. J. Med. 372(1), 30–39 (2015).
Medline CASGoogle Scholar
126 Signorelli J, Shah Gandhi A. Cobimetinib. Ann. Pharmacother. 51(2), 146–153 (2017).
Medline CASGoogle Scholar
127 Ribas A, Gonzalez R, Pavlick A et al. Combination of vemurafenib and cobimetinib in patients with advanced BRAF(V600)-mutated melanoma: a Phase 1b study. Lancet Oncol 15(9), 954–965 (2014).
Medline CASGoogle Scholar
128 Larkin J, Ascierto PA, Dréno B et al. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N. Engl. J. Med. 371(20), 1867–1876 (2014).
Medline CASGoogle Scholar
129 Buchdunger E, Zimmermann J, Mett H et al. Inhibition of the Abl protein-tyrosine kinase in vitro and in vivo by a 2-phenylaminopyrimidine derivative. Cancer Res 56(1), 100–104 (1996).
Medline CASGoogle Scholar
130 Piccaluga PP, Rondoni M, Paolini S et al. Imatinib mesylate in the treatment of hematologic malignancies. Expert Opin. Biol. Ther. 7(10), 1597–1611 (2007).
Medline CASGoogle Scholar
131 Bang YJ, 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 376(9742), 687–697 (2010).
Medline CASGoogle Scholar
132 Lilly MB, Ottmann OG, Shah NP et al. Dasatinib 140 mg once daily versus 70 mg twice daily in patients with Ph-positive acute lymphoblastic leukemia who failed imatinib: results from a Phase 3 study. Am. J. Hematol. 85(3), 164–170 (2010).
Medline CASGoogle Scholar
133 Jabbour E, Lipton JH. A critical review of trials of first-line BCR-ABL inhibitor treatment in patients with newly diagnosed chronic myeloid leukemia in chronic Phase. Clin. Lymphoma Myeloma Leuk. 13(6), 646–656 (2013).
Medline CASGoogle Scholar
134 Blay JY, von Mehren M. Nilotinib: a novel, selective tyrosine kinase inhibitor. Semin. Oncol. 38(Suppl. 1), S3–9; 104 (2011).
Medline CASGoogle Scholar
135 Emole J, Talabi T, Pinilla-Ibarz J. Update on the management of Philadelphia chromosome positive chronic myelogenous leukemia: role of nilotinib. Biologics 10(105), 23–31 (2016).
Medline CASGoogle Scholar
136 Poch Martell M, Sibai H, Deotare U et al. Ponatinib in the therapy of chronic myeloid leukemia. Expert Rev. Hematol. 9(10), 923–932 (2016).
Medline CASGoogle Scholar
137 Parker WT, Yeung DT, Yeoman AL et al. The impact of multiple low-level BCR-ABL1 mutations on response to ponatinib. Blood 127(15), 1870–1880 (2016).
Medline CASGoogle Scholar
138 Cortes JE, Kim DW, Pinilla-Ibarz J et al. A Phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias. N. Engl. J. Med. 369(19), 1783–1796 (2013).
Medline CASGoogle Scholar
139 Cortes J, Kim DW, Pinilla-Ibarz J et al. Dynamics of BCR-ABL kinase domain mutations in chronic myeloid leukemia after sequential treatment with multiple tyrosine kinase inhibitors. Blood 110(12), 4005–4011 (2007).
Medline CASGoogle Scholar
140 Cortes JE, Kantarjian H, Shah NP et al. Ponatinib in refractory Philadelphia chromosome-positive leukemias. N. Engl. J. Med. 367(22), 2075–2088 (2012).
Medline CASGoogle Scholar
141 Stone RM, DeAngelo DJ, Klimek V et al. Patients with acute myeloid leukemia and an activating mutation in FLT3 respond to a small-molecule FLT3 tyrosine kinase inhibitor, PKC412. Blood 105(1), 54–60 (2005).
Medline CASGoogle Scholar
142 Leget GA, Czuczman MS. Use of rituximab, the new FDA-approved antibody. Curr. Opin. Oncol. 10(6), 548–551 (1998).
Medline CASGoogle Scholar
143 James DF, Kipps TJ. Rituximab in chronic lymphocytic leukemia. Adv Ther. 28(7), 534–554 (2011).
Medline CASGoogle Scholar
144 Bryan J, Borthakur G. Role of rituximab in first-line treatment of chronic lymphocytic leukemia. Ther. Clin. Risk Manag. 7, 1–11 (2010).
MedlineGoogle Scholar
145 Roberts AW, Davids MS, Davids JM et al. Targeting BCL2 with venetoclax in relapsed chronic lymphocytic leukemia. N. Engl. J. Med. 374(4), 311–322 (2016).
Medline CASGoogle Scholar
146 Jones AK, Freise KJ, Agarwal SK, Humerickhouse RA, Wong SL, Salem AH. Clinical predictors of venetoclax pharmacokinetics in chronic lymphocytic leukemia and non-Hodgkin's lymphoma patients: a pooled population pharmacokinetic analysis. AAPS J. 18(5), 1192–1202 (2016).
Medline CASGoogle Scholar
147 Golas JM, Arndt K, Etienne C et al. SKI-606, a 4-anilino-3-quinolinecarbonitrile dual inhibitor of Src and Abl kinases, is a potent antiproliferative agent against chronic myelogenous leukemia cells in culture and causes regression of K562 xenografts in nude mice. Cancer Res. 63(2), 375–381 (2003).
Medline CASGoogle Scholar
148 Cortes JE, Kim DW, Kantarjian HM et al. Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: results from the BELA trial. J. Clin. Oncol. 30(28), 3486–3492 (2012).
Medline CASGoogle Scholar
149 Gambacorti-Passerini C, Cortes JE, Lipton JH et al. Safety of bosutinib versus imatinib in the Phase 3 BELA trial in newly diagnosed chronic Phase chronic myeloid leukemia. Am. J. Hematol. 89(10), 947–953 (2014).
Medline CASGoogle Scholar
150 O'Hare T, Walters DK, Stoffregen EP et al. In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants. Cancer Res. 65(11), 4500–4505 (2005).
MedlineGoogle Scholar
151 Kantarjian H, Shah NP, Hochhaus A et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N. Engl. J. Med. 362(24), 2260–2270 (2010).
Medline CASGoogle Scholar
152 Heinrich MC, Griffith DJ, Druker BJ, Wait CL, Ott KA, Zigler AJ. Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor. Blood 96(3), 925–932 (2000).
Medline CASGoogle Scholar
153 Balaian E, Schuster C, Schönefeldt C et al. Selective expansion of regulatory T cells during lenalidomide treatment of myelodysplastic syndrome with isolated deletion 5q. Ann. Hematol. 95(11), 1805–1810 (2016).
Medline CASGoogle Scholar
154 Hainsworth JD, Litchy S, Burris HA 3rd et al. Rituximab as first-line and maintenance therapy for patients with indolent non-Hodgkin's lymphoma. J. Clin. Oncol. 20(20), 4261–4267 (2002).
Medline CASGoogle Scholar
155 van Oers MH, Van Glabbeke M, Giurgea L et al. Rituximab maintenance treatment of relapsed/resistant follicular non-Hodgkin's lymphoma: long-term outcome of the EORTC 20981 Phase III randomized intergroup study. J. Clin. Oncol. 28(17), 2853–2858 (2010).
Medline CASGoogle Scholar
156 Tobinai K. Rituximab and other emerging monoclonal antibody therapies for lymphoma. Expert Opin. Emerg. Drugs 7(2), 289–302 (2002).
Medline CASGoogle Scholar
157 O'Brien S, Jones JA, Coutre SE et al. Ibrutinib for patients with relapsed or refractory chronic lymphocytic leukaemia with 17p deletion (RESONATE-17): a Phase 2, open-label, multicentre study. Lancet Oncol. 17(10), 1409–1418 (2016).
MedlineGoogle Scholar
158 Thieblemont C. [Ibrutinib: a new drug of B-cell malignancies]. Bull. Cancer 102(6, Suppl. 1), S85–S90 (2015).
MedlineGoogle Scholar
159 Cameron F, Sanford M. Ibrutinib: first global approval. Drugs 74(2), 263–271 (2014).
Medline CASGoogle Scholar
160 Dimopoulos MA, Kastritis E, Ghobrial IM. Waldenstrom's macroglobulinemia: a clinical perspective in the era of novel therapeutics. Ann. Oncol. 27(2), 233–240 (2016).
Medline CASGoogle Scholar
161 Gavriatopoulou M, Terpos E, Kastritis E, Dimopoulos MA. Current treatment options and investigational drugs for Waldenstrom's macroglobulinemia. Expert Opin. Investig. Drugs 26(2), 197–205 (2017).
Medline CASGoogle Scholar
162 Daily Med. https://dailymed.nlm.nih.gov/dailymed/drugInfo.
Google Scholar
163 FDA. www.FDA.gov.
Google Scholar
164 Biankin AV, Piantadosi S, Hollingsworth SJ. Patient-centric trials for therapeutic development in precision oncology. Nature 526(7573), 361–370 (2015).
Medline CASGoogle Scholar
165 Singer E. Personalized medicine prompts push to redesign clinical trials. Nat. Med. 11(5), 462 (2005).
Medline CASGoogle Scholar
166 Sleijfer S, Bogaerts J, Siu LL. Designing transformative clinical trials in the cancer genome era. J. Clin. Oncol. 31(15), 1834–1841 (2013).
MedlineGoogle Scholar
167 Sargent D, Allegra C. Issues in clinical trial design for tumor marker studies. Semin. Oncol. 29(3), 222–230 (2002).
MedlineGoogle Scholar
168 Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin. Pharmacol. Ther. 69(3), 89–95 (2001).
MedlineGoogle Scholar
169 FDA – US Food and Drug Administration: guideline for industry clinical trial endpoints for the approval of cancer drugs and biologics. www.fda.gov/cder/guidance/index.htm.
Google Scholar
170 Hoering A, Leblanc M, Crowley JJ. Randomized Phase III clinical trial designs for targeted agents. Clin. Cancer. Res. 14(14), 4358–4367 (2008).
Medline CASGoogle Scholar
171 Freidlin B, Korn EL. Biomarker enrichment strategies: matching trial design to biomarker credentials. Nat. Rev. Clin. Oncol. 11(2), 81–90 (2014).
MedlineGoogle Scholar
172 Maitournam A, Simon R. On the efficiency of targeted clinical trials. Stat. Med. 24(3), 329–339 (2005).
Medline CASGoogle Scholar
173 Freidlin B, McShane LM, Korn EL. Randomized clinical trials with biomarkers: design issues. J. Natl Cancer Inst. 102(3), 152–160 (2010).
Medline CASGoogle Scholar
174 Kim ES, Hirsh V, Mok T et al. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised Phase III trial. Lancet 372(9652), 1809–1818 (2008).
Medline CASGoogle Scholar
175 Bang YJ, 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 376(9742), 687–697 (2010).
Medline CASGoogle Scholar
176 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. 29(25), 3366–3373 (2011).
Medline CASGoogle Scholar
177 Simon N, Simon R. Adaptive enrichment designs for clinical trials. Biostatistics 14(4), 613–625 (2013).
MedlineGoogle Scholar
178 Mandrekar SJ, Dahlberg SE, Simon R. Improving clinical trial efficiency: thinking outside the box. Am. Soc. Clin. Oncol. Educ. Book e141–7 (2015).
MedlineGoogle Scholar
179 Renfro LA, Sargent DJ. Statistical controversies in clinical research: basket trials, umbrella trials, and other master protocols: a review and examples. Ann. Oncol. 28(1), 34–43 (2016).
Google Scholar
180 Rubin EH, Anderson KM, Gause CK. The BATTLE trial: a bold step toward improving the efficiency of biomarker-based drug development. Cancer Discov. 1(1), 17–20 (2011).
Medline CASGoogle Scholar
181 Kim ES, Herbst RS, Wistuba II et al. The BATTLE trial: personalizing therapy for lung cancer. Cancer Discov. 1(1), 44–53 (2011).
Medline CASGoogle Scholar
182 Conley BA, Doroshow JH. Molecular analysis for therapy choice: NCI MATCH. Semin. Oncol. 41(3), 297–299 (2014).
MedlineGoogle Scholar
183 Ferrarotto R, Redman MW, Gandara DR, Herbst RS, Papadimitrakopoulou VA. Lung-MAP – framework, overview, and design principles. Chin. Clin. Oncol. 4(3), 36 (2015).
MedlineGoogle Scholar
184 Oxnard GR, Watt C, Wigle D, Boughey JC. Biomarker-driven adjuvant targeted therapy for NSCLC-the ALCHEMIST trials. Bull. Am. Coll. Surg. 100(9), 25–27 (2015).
MedlineGoogle Scholar
185 Alden RS, Mandrekar SJ, Oxnard GR. Designing a definitive trial for adjuvant targeted therapy in genotype defined lung cancer: the ALCHEMIST trials. Chin. Clin. Oncol. 4(3), 37 (2015).
MedlineGoogle Scholar
186 DeVita VT Jr, Chu E. A history of cancer chemotherapy. Cancer Res. 68(21), 8643–8653 (2008).
Medline CASGoogle Scholar
187 Frei E III, Holland JF, Schneiderman MA et al. A comparative study of two regimens of combination chemotherapy in acute leukemia. Blood 13(12), 1126–1148 (1958).
MedlineGoogle Scholar
188 Siegel RL, Miller KD, Jemal AD. Cancer statistics, 2016. CA Cancer. J. Clin. 66(1), 7–30 (2016).
MedlineGoogle Scholar
189 Mallarkey G, Coombes RC. Targeted therapies in medical oncology: successes, failures and next steps. Ther. Adv. Med. Oncol. 5(1), 5–16 (2013).
MedlineGoogle Scholar
190 Hay M, Thomas DW, Craighead JL, Economides C, Rosenthal J et al. Clinical development success rates for investigational drugs. Nat. Biotechnol. 32(1), 40–51 (2014).
Medline CASGoogle Scholar
191 Schwaederle M, Husain H, Fanta PT. Detection rate of actionable mutations in diverse cancers using a biopsy-free (blood) circulating tumor cell DNA assay. Oncotarget 7(9), 9707–9717 (2016).
MedlineGoogle Scholar
192 Kris MG, Johnson BE, Berry LD et al. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA 311(19), 1998–2006 (2014).
Medline CASGoogle Scholar
193 Chouaid C, Le Caer H, Corre R et al. Cost analysis of erlotinib versus chemotherapy for first-line treatment of non-small-cell lung cancer in frail elderly patients participating in a prospective Phase 2 study (GFPC 0505). Clin. Lung Cancer 14(2), 103–107 (2013).
MedlineGoogle Scholar
194 Carlson JJ, Garrison LP, Ramsey SD, Veenstra DL. The potential clinical and economic outcomes of pharmacogenomic approaches to EGFR-tyrosine kinase inhibitor therapy in non-small-cell lung cancer. Value Health 12(1), 20–27 (2009).
MedlineGoogle Scholar
195 Handorf EA, McElligott S, Vachani A et al. Cost–effectiveness of personalized therapy for first-line treatment of stage IV and recurrent incurable adenocarcinoma of the lung. J. Oncol. Pract. 8(5), 267–274 (2012).
MedlineGoogle Scholar
196 Human Genome Project. www.genome.gov/12011238/an-overview-of-the-human-genome-project/.
Google Scholar
197 The Cancer Genome Atlas (TCGA). . www.genome.gov/12011238/an-overview-of-the-human-genome-project/.
Google Scholar

Vol. 18, No. 16

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Received 25 May 2017

Accepted 24 July 2017

Published online 24 October 2017

Published in print November 2017

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Financial & competing interests disclosure

This work was supported by The Cancer Prevention and Research Institute of Texas (RP1100584) and the Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy (1U01 CA180964). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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Precision oncology: neither a silver bullet nor a dream

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