Challenges in molecular testing in non-small-cell lung cancer patients with advanced disease

The Lancet

Volumn 388, Issue 10048, 2016, Pages 1002-1011

  Hiley, Crispin T ^a,b   Le Quesne, John ^c   Santis, George ^b   Sharpe, Rowena ^d   de Castro, David Gonzalez ^e,f   Middleton, Gary ^g,h   Swanton, Charles ^a,i  

^a THE FRANCIS CRICK INSTITUTE   (United Kingdom)

^b KING'S COLLEGE LONDON   (United Kingdom)

^c UNIVERSITY OF LEICESTER   (United Kingdom)

^d IMPERIAL CANCER RESEARCH FUND   (United Kingdom)

^e ROYAL MARSDEN HOSPITAL   (United Kingdom)

^f QUEEN'S UNIVERSITY BELFAST   (United Kingdom)

^g UNIVERSITY OF BIRMINGHAM   (United Kingdom)

^h QUEEN ELIZABETH HOSPITAL   (United Kingdom)

ⁱ UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ANAPLASTIC LYMPHOMA KINASE; BIOLOGICAL MARKER; EPIDERMAL GROWTH FACTOR RECEPTOR; PROGRAMMED DEATH 1 LIGAND 1; TUMOR MARKER; PROTEIN TYROSINE KINASE;

ADVANCED CANCER; CANCER DIAGNOSIS; CANCER PATIENT; CANCER RESISTANCE; CLINICAL PRACTICE; CLINICAL TRIAL (TOPIC); FUSION GENE; GENE MUTATION; GENETIC HETEROGENEITY; GENETIC VARIABILITY; HISTOLOGY; HUMAN; MOLECULAR DIAGNOSIS; MOLECULAR DIAGNOSTICS; NEXT GENERATION SEQUENCING; NON SMALL CELL LUNG CANCER; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SAMPLING; GENETICS; HIGH THROUGHPUT SEQUENCING; LUNG TUMOR; MUTATION; PATHOLOGY; PROCEDURES; SEVERITY OF ILLNESS INDEX;

BIOMARKERS, TUMOR; CARCINOMA, NON-SMALL-CELL LUNG; HIGH-THROUGHPUT NUCLEOTIDE SEQUENCING; HUMANS; LUNG NEOPLASMS; MUTATION; RECEPTOR PROTEIN-TYROSINE KINASES; RECEPTOR, EPIDERMAL GROWTH FACTOR; SEVERITY OF ILLNESS INDEX;

EID: 84989162800     PISSN: 01406736     EISSN: 1474547X     Source Type: Journal    
DOI: 10.1016/S0140-6736(16)31340-X     Document Type: Review

References (132)

1. 1 Lung cancer key statistics, 2015, Cancer Research UK, United Kingdom.
2. 2 Adler, IA, Primary malignant growths of the lung and bronchi, 1912, Longmans, Green and Company, New York.
3. 3 Cancer Genome Atlas Research Network. Comprehensive genomic characterization of squamous cell lung cancers. Nature 489 (2012), 519–525.
4. 4 Cancer Genome Atlas Research Network. Comprehensive molecular profiling of lung adenocarcinoma. Nature 511 (2014), 543–550.
5. 5 Swanton, C, Govindan, R, Clinical implications of genomic discoveries in lung cancer. N Engl J Med 374 (2016), 1864–1873.
6. 6 Schiller, JH, Harrington, D, Belani, CP, et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 346 (2002), 92–98.
7. 7 Scagliotti, GV, De Marinis, F, Rinaldi, M, et al. Phase III randomized trial comparing three platinum-based doublets in advanced non-small-cell lung cancer. J Clin Oncol 20 (2002), 4285–4291.
8. 8 Kelly, K, Crowley, J, Bunn, PA Jr, et al. Randomized phase III trial of paclitaxel plus carboplatin versus vinorelbine plus cisplatin in the treatment of patients with advanced non—small-cell lung cancer: a Southwest Oncology Group trial. J Clin Oncol 19 (2001), 3210–3218.
9. 9 Mok, TS, Wu, YL, Thongprasert, S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 361 (2009), 947–957.
10. 10 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 (2012), 239–246.
11. 11 Ciuleanu, T, Brodowicz, T, Zielinski, C, et al. Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study. Lancet 374 (2009), 1432–1440.
12. 12 Scagliotti, GV, Parikh, P, von Pawel, J, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol 26 (2008), 3543–3551.
13. 13 Reck, M, Popat, S, Reinmuth, N, et al. Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2 (2014), iii27–iii39.
14. 14 Masters, GA, Temin, S, Azzoli, CG, et al. Systemic Therapy for Stage IV Non-Small-Cell Lung Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol 33 (2015), 3488–3515.
15. 15 Kerr, KM, Bubendorf, L, Edelman, MJ, et al. Second ESMO consensus conference on lung cancer: pathology and molecular biomarkers for non-small-cell lung cancer. Ann Oncol 25 (2014), 1681–1690.
16. 16 Terry, J, Leung, S, Laskin, J, Leslie, KO, Gown, AM, Ionescu, DN, Optimal immunohistochemical markers for distinguishing lung adenocarcinomas from squamous cell carcinomas in small tumor samples. Am J Surg Pathol 34 (2010), 1805–1811.
17. 17 Zhang, C, Schmidt, LA, Hatanaka, K, Thomas, D, Lagstein, A, Myers, JL, Evaluation of napsin A, TTF-1, p63, p40, and CK5/6 immunohistochemical stains in pulmonary neuroendocrine tumors. Am J Clin Pathol 142 (2014), 320–324.
18. 18 Jamal-Hanjani, M, Hackshaw, A, Ngai, Y, et al. Tracking genomic cancer evolution for precision medicine: the lung TRACERx study. PLoS Biology, 12, 2014, e1001906.
19. 19 Audit, NLC, NLCA Annual Report, 2015, Royal College of Physicians, London.
20. 20 Rivera, MP, Mehta, AC, Wahidi, MM, Establishing the diagnosis of lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 143:suppl (2013), e142S–e165S.
21. 21 Kinsey, CM, Arenberg, DA, Endobronchial ultrasound-guided transbronchial needle aspiration for non-small cell lung cancer staging. Am J Respir Crit Care Med 189 (2014), 640–649.
22. 22 Navani, N, Brown, JM, Nankivell, M, et al. Suitability of endobronchial ultrasound-guided transbronchial needle aspiration specimens for subtyping and genotyping of non-small cell lung cancer: a multicenter study of 774 patients. Am J Respir Crit Care Med 185 (2012), 1316–1322.
23. 23 Santis, G, Angell, R, Nickless, G, et al. Screening for EGFR and KRAS mutations in endobronchial ultrasound derived transbronchial needle aspirates in non-small cell lung cancer using COLD-PCR. PLoS One, 6, 2011, e25191.
24. 24 Nakajima, T, Yasufuku, K, Nakagawara, A, Kimura, H, Yoshino, I, Multigene mutation analysis of metastatic lymph nodes in non-small cell lung cancer diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration. Chest 140 (2011), 1319–1324.
25. 25 van Eijk, R, Licht, J, Schrumpf, M, et al. Rapid KRAS, EGFR, BRAF and PIK3CA mutation analysis of fine needle aspirates from non-small-cell lung cancer using allele-specific qPCR. PLoS One, 6, 2011, e17791.
26. 26 Kanagal-Shamanna, R, Portier, BP, Singh, RR, et al. Next-generation sequencing-based multi-gene mutation profiling of solid tumors using fine needle aspiration samples: promises and challenges for routine clinical diagnostics. Mod Pathol 27 (2014), 314–327.
27. 27 Qiu, T, Guo, H, Zhao, H, Wang, L, Zhang, Z, Next-generation sequencing for molecular diagnosis of lung adenocarcinoma specimens obtained by fine needle aspiration cytology. Sci Rep, 5, 2015, 11317.
28. 28 Kris, MG, Natale, RB, Herbst, RS, 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. JAMA 290 (2003), 2149–2158.
29. 29 Fukuoka, M, Yano, S, Giaccone, G, 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) [corrected]. J Clin Oncol 21 (2003), 2237–2246.
30. 30 Thatcher, N, Chang, A, Parikh, P, et al. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet 366 (2005), 1527–1537.
31. 31 Giaccone, G, Herbst, RS, Manegold, C, et al. Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial—INTACT 1. J Clin Oncol 22 (2004), 777–784.
32. 32 Lynch, TJ, Bell, DW, Sordella, R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 350 (2004), 2129–2139.
33. 33 Paez, JG, Janne, PA, Lee, JC, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304 (2004), 1497–1500.
34. 34 Pao, W, Miller, V, Zakowski, M, et al. EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci USA 101 (2004), 13306–13311.
35. 35 Bell, DW, Lynch, TJ, Haserlat, SM, et al. Epidermal growth factor receptor mutations and gene amplification in non-small-cell lung cancer: molecular analysis of the IDEAL/INTACT gefitinib trials. J Clin Oncol 23 (2005), 8081–8092.
36. 36 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 (2015), 141–151.
37. 37 Sharma, SV, Bell, DW, Settleman, J, Haber, DA, Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer 7 (2007), 169–181.
38. 38 Pao, W, Miller, VA, Politi, KA, et al. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med, 2, 2005, e73.
39. 39 Inukai, M, Toyooka, S, Ito, S, et al. Presence of epidermal growth factor receptor gene T790M mutation as a minor clone in non-small cell lung cancer. Cancer Res 66 (2006), 7854–7858.
40. 40 Su, KY, Chen, HY, Li, KC, et al. Pretreatment epidermal growth factor receptor (EGFR) T790M mutation predicts shorter EGFR tyrosine kinase inhibitor response duration in patients with non-small-cell lung cancer. J Clin Oncol 30 (2012), 433–440.
41. 41 Hata, AN, Niederst, MJ, Archibald, HL, et al. Tumor cells can follow distinct evolutionary paths to become resistant to epidermal growth factor receptor inhibition. Nat Med 22 (2016), 262–269.
42. 42 Janne, PA, Yang, JC, Kim, DW, et al. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. N Engl J Med 372 (2015), 1689–1699.
43. 43 Sequist, LV, Soria, JC, Goldman, JW, et al. Rociletinib in EGFR-mutated non-small-cell lung cancer. N Engl J Med 372 (2015), 1700–1709.
44. 44 Sequist, LV, Waltman, BA, Dias-Santagata, D, et al. Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci Transl Med, 3, 2011, 75ra26.
45. 45 Piotrowska, Z, Niederst, MJ, Karlovich, CA, et al. Heterogeneity underlies the emergence of EGFRT790 wild-type clones following treatment of T790M-positive cancers with a third-generation EGFR inhibitor. Cancer Discov 5 (2015), 713–722.
46. 46 Thress, KS, Paweletz, CP, Felip, E, et al. Acquired EGFR C797S mutation mediates resistance to AZD9291 in non-small cell lung cancer harboring EGFR T790M. Nat Med 21 (2015), 560–562.
47. 47 Williams, C, Ponten, F, Moberg, C, et al. A high frequency of sequence alterations is due to formalin fixation of archival specimens. Am J Pathol 155 (1999), 1467–1471.
48. 48 Pirker, R, Herth, FJ, Kerr, KM, et al. Consensus for EGFR mutation testing in non-small cell lung cancer: results from a European workshop. J Thorac Oncol 5 (2010), 1706–1713.
49. 49 Lindeman, NI, Cagle, PT, Beasley, MB, et al. Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. J Thorac Oncol 8 (2013), 823–859.
50. 50 Schmitt, MW, Kennedy, SR, Salk, JJ, Fox, EJ, Hiatt, JB, Loeb, LA, Detection of ultra-rare mutations by next-generation sequencing. Proc Natl Acad Sci USA 109 (2012), 14508–14513.
51. 51 Wong, SQ, Li, J, Tan, AY, et al. Sequence artefacts in a prospective series of formalin-fixed tumours tested for mutations in hotspot regions by massively parallel sequencing. BMC Med Genomics, 7, 2014, 23.
52. 52 Yang, JC, Sequist, LV, Geater, SL, et al. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol 16 (2015), 830–838.
53. 53 Lai, Z, Markovets, A, Ahdesmaki, M, et al. VarDict: a novel and versatile variant caller for next-generation sequencing in cancer research. Nucleic Acids Res, 44, 2016, e108.
54. 54 O'Rawe, J, Jiang, T, Sun, G, et al. Low concordance of multiple variant-calling pipelines: practical implications for exome and genome sequencing. Genome Med, 5, 2013, 28.
55. 55 Rehm, HL, Bale, SJ, Bayrak-Toydemir, P, et al. ACMG clinical laboratory standards for next-generation sequencing. Genet Med 15 (2013), 733–747.
56. 56 Park, S, Holmes-Tisch, AJ, Cho, EY, et al. Discordance of molecular biomarkers associated with epidermal growth factor receptor pathway between primary tumors and lymph node metastasis in non-small cell lung cancer. J Thorac Oncol 4 (2009), 809–815.
57. 57 Zhang, J, Fujimoto, J, Zhang, J, et al. Intratumor heterogeneity in localized lung adenocarcinomas delineated by multiregion sequencing. Science 346 (2014), 256–259.
58. 58 de Bruin, EC, McGranahan, N, Mitter, R, et al. Spatial and temporal diversity in genomic instability processes defines lung cancer evolution. Science 346 (2014), 251–256.
59. 59 Soda, M, Choi, YL, Enomoto, M, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 448 (2007), 561–566.
60. 60 Kwak, EL, Bang, YJ, Camidge, DR, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med 363 (2010), 1693–1703.
61. 61 Koivunen, JP, Mermel, C, Zejnullahu, K, et al. EML4-ALK fusion gene and efficacy of an ALK kinase inhibitor in lung cancer. Clin Cancer Res 14 (2008), 4275–4283.
62. 62 Zhao, W, Choi, YL, Song, JY, et al. ALK, ROS1 and RET rearrangements in lung squamous cell carcinoma are very rare. Lung Cancer 94 (2016), 22–27.
63. 63 Shaw, AT, Kim, DW, Nakagawa, K, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med 368 (2013), 2385–2394.
64. 64 Solomon, BJ, Mok, T, Kim, DW, et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med 371 (2014), 2167–2177.
65. 65 Shaw, AT, Ou, SH, Bang, YJ, et al. Crizotinib in ROS1-rearranged non-small-cell lung cancer. N Engl J Med 371 (2014), 1963–1971.
66. 66 Takeuchi, K, Soda, M, Togashi, Y, et al. RET, ROS1 and ALK fusions in lung cancer. Nat Med 18 (2012), 378–381.
67. 67 Vaishnavi, A, Capelletti, M, Le, AT, et al. Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer. Nat Med 19 (2013), 1469–1472.
68. 68 Iyevleva, AG, Raskin, GA, Tiurin, VI, et al. Novel ALK fusion partners in lung cancer. Cancer Lett 362 (2015), 116–121.
69. 69 Takeuchi, K, Choi, YL, Togashi, Y, et al. KIF5B-ALK, a novel fusion oncokinase identified by an immunohistochemistry-based diagnostic system for ALK-positive lung cancer. Clin Cancer Res 15 (2009), 3143–3149.
70. 70 Yoshida, A, Tsuta, K, Nakamura, H, et al. Comprehensive histologic analysis of ALK-rearranged lung carcinomas. Am J Surg Pathol 35 (2011), 1226–1234.
71. 71 Tsao, MS, Hirsch, FR, Yatabe, Y, IASLC Atlas of ALK testing in lung cancer, 2013, International Association for the Study of Lung Cancer Press, Aurora, CO.
72. 72 Takeuchi, K, Togashi, Y, Kamihara, Y, et al. Prospective and clinical validation of ALK immunohistochemistry: results from the phase I/II study of alectinib for ALK-positive lung cancer (AF-001JP study). Ann Oncol 27 (2016), 185–192.
73. 73 Davare, MA, Tognon, CE, Detecting and targetting oncogenic fusion proteins in the genomic era. Biol Cell 107 (2015), 111–129.
74. 74 Drilon, A, Wang, L, Arcila, ME, et al. Broad, hybrid capture-based next-generation sequencing identifies actionable genomic alterations in lung adenocarcinomas otherwise negative for such alterations by other genomic testing approaches. Clin Cancer Res 21 (2015), 3631–3639.
75. 75 Jang, JS, Wang, X, Vedell, PT, et al. Custom gene capture and next generation sequencing to resolve discordant ALK status by FISH and IHC in lung adenocarcinoma. J Thorac Oncol, 2016, 10.1016/j.jtho.2016.06.001 published online June 22.
76. 76 Hou, L, Wu, C, Comparative study of ALK rearrangement between primary tumor and paired lymphatic metastasis in NSCLC patients. J Clin Oncol, 33(suppl), 2015, e19134 (abstr).
77. 77 Cai, W, Lin, D, Wu, C, et al. Intratumoral heterogeneity of ALK-rearranged and ALK/EGFR coaltered lung adenocarcinoma. J Clin Oncol 33 (2015), 3701–3709.
78. 78 Birkbak, NJ, Hiley, CT, Swanton, C, Evolutionary precision medicine: a role for repeat epidermal growth factor receptor analysis in ALK-rearranged lung adenocarcinoma?. J Clin Oncol 33 (2015), 3681–3683.
79. 79 Sasaki, T, Koivunen, J, Ogino, A, et al. A novel ALK secondary mutation and EGFR signaling cause resistance to ALK kinase inhibitors. Cancer Res 71 (2011), 6051–6060.
80. 80 Choi, YL, Soda, M, Yamashita, Y, et al. EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors. N Engl J Med 363 (2010), 1734–1739.
81. 81 Doebele, RC, Pilling, AB, Aisner, DL, et al. Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non-small cell lung cancer. Clin Cancer Res 18 (2012), 1472–1482.
82. 82 Katayama, R, Shaw, AT, Khan, TM, et al. Mechanisms of acquired crizotinib resistance in ALK-rearranged lung cancers. Sci Transl Med, 4, 2012, 120ra17.
83. 83 Shaw, AT, Friboulet, L, Leshchiner, I, et al. Resensitization to crizotinib by the lorlatinib ALK resistance mutation L1198F. N Engl J Med 374 (2016), 54–61.
84. 84 Barlesi, F, Mazieres, J, Merlio, JP, et al. Routine molecular profiling of patients with advanced non-small-cell lung cancer: results of a 1-year nationwide programme of the French Cooperative Thoracic Intergroup (IFCT). Lancet 387 (2016), 1415–1426.
85. 85 Kris, MG, Johnson, BE, Berry, LD, et al. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA 311 (2014), 1998–2006.
86. 86 Konig, K, Peifer, M, Fassunke, J, et al. Implementation of amplicon parallel sequencing leads to improvement of diagnosis and therapy of lung cancer patients. J Thorac Oncol 10 (2015), 1049–1057.
87. 87 Dienstmann, R, Jang, IS, Bot, B, Friend, S, Guinney, J, Database of genomic biomarkers for cancer drugs and clinical targetability in solid tumors. Cancer Discov 5 (2015), 118–123.
88. 88 Cerami, E, Gao, J, Dogrusoz, U, et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov 2 (2012), 401–404.
89. 89 Middleton, G, Crack, LR, Popat, S, et al. The National Lung Matrix Trial: translating the biology of stratification in advanced non-small-cell lung cancer. Ann Oncol 26 (2015), 2464–2469.
90. 90 Pearson, A, Smyth, E, Babina, IS, et al. High-level clonal FGFR amplification and response to FGFR inhibition in a translational clinical trial. Cancer Discov, 2016, 10.1158/2159-8290.CD-15-1246 pulished online May 13.
91. 91 Lopez-Chavez, A, Thomas, A, Rajan, A, et al. Molecular profiling and targeted therapy for advanced thoracic malignancies: a biomarker-derived, multiarm, multihistology phase II basket trial. J Clin Oncol 33 (2015), 1000–1007.
92. 92 Biankin, AV, Piantadosi, S, Hollingsworth, SJ, Patient-centric trials for therapeutic development in precision oncology. Nature 526 (2015), 361–370.
93. 93 Konishi, J, Yamazaki, K, Azuma, M, Kinoshita, I, Dosaka-Akita, H, Nishimura, M, B7-H1 expression on non-small cell lung cancer cells and its relationship with tumor-infiltrating lymphocytes and their PD-1 expression. Clin Cancer Res 10 (2004), 5094–5100.
94. 94 Taube, JM, Anders, RA, Young, GD, et al. Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med, 4, 2012, 127ra37.
95. 95 Gros, A, Robbins, PF, Yao, X, et al. PD-1 identifies the patient-specific CD8(+) tumor-reactive repertoire infiltrating human tumors. J Clin Invest 124 (2014), 2246–2259.
96. 96 Garon, EB, Rizvi, NA, Hui, R, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med 372 (2015), 2018–2028.
97. 97 Herbst, RS, Baas, P, Kim, DW, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 387 (2016), 1540–1550.
98. 98 Borghaei, H, Paz-Ares, L, Horn, L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med 373 (2015), 1627–1639.
99. 99 Brahmer, J, Reckamp, KL, Baas, P, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med 373 (2015), 123–135.
100. 100 Fehrenbacher, L, Spira, A, Ballinger, M, et al. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet 387 (2016), 1837–1846.
101. 101 Taube, JM, Klein, A, Brahmer, JR, et al. Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy. Clin Cancer Res 20 (2014), 5064–5074.
102. 102 Velcheti, V, Schalper, KA, Carvajal, DE, et al. Programmed death ligand-1 expression in non-small cell lung cancer. Lab Invest 94 (2014), 107–116.
103. 103 McLaughlin, J, Han, G, Schalper, KA, et al. Quantitative assessment of the heterogeneity of PD-L1 expression in non-small-cell lung cancer. JAMA Oncol 2 (2016), 46–54.
104. 104 Pardoll, DM, The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 12 (2012), 252–264.
105. 105 Akbay, EA, Koyama, S, Carretero, J, et al. Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung tumors. Cancer Discov 3 (2013), 1355–1363.
106. 106 Rizvi, NA, Hellmann, MD, Snyder, A, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 348 (2015), 124–128.
107. 107 Brown, SD, Warren, RL, Gibb, EA, et al. Neo-antigens predicted by tumor genome meta-analysis correlate with increased patient survival. Genome Res 24 (2014), 743–750.
108. 108 McGranahan, N, Furness, AJ, Rosenthal, R, et al. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science 351 (2016), 1463–1469.
109. 109 Patel, SP, Kurzrock, R, PD-L1 Expression as a Predictive Biomarker in Cancer Immunotherapy. Mol Cancer Ther 14 (2015), 847–856.
110. 110 Herbst, RS, Soria, JC, Kowanetz, M, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 515 (2014), 563–567.
111. 111 Shaw, EC, Hanby, AM, Wheeler, K, et al. Observer agreement comparing the use of virtual slides with glass slides in the pathology review component of the POSH breast cancer cohort study. J Clin Pathol 65 (2012), 403–408.
112. 112 Favero, F, Joshi, T, Marquard, AM, et al. Sequenza: allele-specific copy number and mutation profiles from tumor sequencing data. Ann Oncol 26 (2015), 64–70.
113. 113 Van Loo, P, Nordgard, SH, Lingjaerde, OC, et al. Allele-specific copy number analysis of tumors. Proc Natl Acad Sci USA 107 (2010), 16910–16915.
114. 114 Yates, LR, Campbell, PJ, Evolution of the cancer genome. Nat Rev Genet 13 (2012), 795–806.
115. 115 Hiley, C, de Bruin, E, McGranahan, N, Swanton, C, Deciphering intratumor heterogeneity and temporal acquisition of driver events to refine precision medicine. Genome Biol, 15, 2014, 453.
116. 116 Melchor, L, Brioli, A, Wardell, CP, et al. Single-cell genetic analysis reveals the composition of initiating clones and phylogenetic patterns of branching and parallel evolution in myeloma. Leukemia 28 (2014), 1705–1715.
117. 117 Fisher, R, Horswell, S, Rowan, A, et al. Development of synchronous VHL syndrome tumors reveals contingencies and constraints to tumor evolution. Genome Biol, 15, 2014, 433.
118. 118 Juric, D, Castel, P, Griffith, M, et al. Convergent loss of PTEN leads to clinical resistance to a PI(3)Kalpha inhibitor. Nature 518 (2015), 240–244.
119. 119 Gundem, G, Van Loo, P, Kremeyer, B, et al. The evolutionary history of lethal metastatic prostate cancer. Nature 520 (2015), 353–357.
120. 120 Jamal-Hanjani, M, Wilson, GA, Horswell, S, et al. Detection of ubiquitous and heterogeneous mutations in cell-free DNA from patients with early-stage non-small-cell lung cancer. Ann Oncol 27 (2016), 862–867.
121. 121 Murtaza, M, Dawson, SJ, Tsui, DW, et al. Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature 497 (2013), 108–112.
122. 122 Oxnard, GR, Paweletz, CP, Kuang, Y, et al. Noninvasive detection of response and resistance in EGFR-mutant lung cancer using quantitative next-generation genotyping of cell-free plasma DNA. Clin Cancer Res 20 (2014), 1698–1705.
123. 123 Thress, KS, Brant, R, Carr, TH, et al. EGFR mutation detection in ctDNA from NSCLC patient plasma: A cross-platform comparison of leading technologies to support the clinical development of AZD9291. Lung Cancer 90 (2015), 509–515.
124. 124 Hou, JM, Krebs, M, Ward, T, et al. Circulating tumor cells as a window on metastasis biology in lung cancer. Am J Pathol 178 (2011), 989–996.
125. 125 Krebs, MG, Sloane, R, Priest, L, et al. Evaluation and prognostic significance of circulating tumor cells in patients with non-small-cell lung cancer. J Clin Oncol 29 (2011), 1556–1563.
126. 126 Maheswaran, S, Sequist, LV, Nagrath, S, et al. Detection of mutations in EGFR in circulating lung-cancer cells. N Engl J Med 359 (2008), 366–377.
127. 127 Lohr, JG, Adalsteinsson, VA, Cibulskis, K, et al. Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer. Nat Biotechnol 32 (2014), 479–484.
128. 128 Hodgkinson, CL, Morrow, CJ, Li, Y, et al. Tumorigenicity and genetic profiling of circulating tumor cells in small-cell lung cancer. Nat Med 20 (2014), 897–903.
129. 129 Diaz, LA Jr, Bardelli, A, Liquid biopsies: genotyping circulating tumor DNA. J Clin Oncol 32 (2014), 579–586.
130. 130 Alix-Panabieres, C, Pantel, K, Challenges in circulating tumour cell research. Nat Rev Cancer 14 (2014), 623–631.
131. 131 Alix-Panabieres, C, Pantel, K, Clinical applications of circulating tumor cells and circulating tumor DNA as liquid biopsy. Cancer Discov 6 (2016), 479–491.
132. 132 Schwarzenbach, H, Hoon, DS, Pantel, K, Cell-free nucleic acids as biomarkers in cancer patients. Nat Rev Cancer 11 (2011), 426–437.