Clinicopathologic features of advanced squamous NSCLC

Journal of Thoracic Oncology

Volumn 11, Issue 9, 2016, Pages 1411-1422

  Socinski, Mark A ^a   Obasaju, Coleman ^b   Gandara, David ^c   Hirsch, Fred R ^d   Bonomi, Philip ^e   Bunn, Paul ^d   Kim, Edward S ^f   Langer, Corey J ^g   Natale, Ronald B ^h   Novello, Silvia ⁱ   Paz Ares, Luis ^j   Pérol, Maurice ^k   Reck, Martin ^l   Ramalingam, Suresh S ^m   Reynolds, Craig H ⁿ   Spigel, David R ^o   Stinchcombe, Thomas E ^p   Wakelee, Heather ^q   Mayo, Carlos ^b   Thatcher, Nick ^r  

^a UNIVERSITY OF PITTSBURGH MEDICAL CENTER   (United States)

^b ELI LILLY AND COMPANY   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d UNIVERSITY OF COLORADO CANCER CENTER   (United States)

^e RUSH UNIVERSITY MEDICAL CENTER   (United States)

^f LEVINE CANCER INSTITUTE   (United States)

^g UNIVERSITY OF PENNSYLVANIA   (United States)

^h Department of Hematology Oncology Cedars Sinai Comprehensive Cancer Center   (United States)

ⁱ UNIVERSITY OF TURIN   (Italy)

^j UNIVERSITY OF SEVILLE   (Spain)

^k CENTRE LÉON BÉRARD   (France)

^l Mitglied im DZL   (Germany)

^m EMORY UNIVERSITY   (United States)

ⁿ US Oncology   (United States)

^o SARAH CANNON RESEARCH INSTITUTE   (United States)

^p UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^q STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^r CHRISTIE HOSPITAL   (United Kingdom)

more..

Author keywords

Etiology; Histologic subtype; NSCLC; Squamous cell lung cancer

Indexed keywords

CANCER EPIDEMIOLOGY; CANCER PATIENT; CLINICAL FEATURE; COMORBIDITY; HISTOPATHOLOGY; HUMAN; MOLECULAR BIOLOGY; OUTCOME ASSESSMENT; PRIORITY JOURNAL; REVIEW; SQUAMOUS CELL LUNG CARCINOMA; CARCINOMA, NON-SMALL-CELL LUNG; GENETICS; LUNG NEOPLASMS; MUTATION; PATHOLOGY; SMOKING; SQUAMOUS CELL CARCINOMA;

EPIDERMAL GROWTH FACTOR RECEPTOR;

CARCINOMA, NON-SMALL-CELL LUNG; CARCINOMA, SQUAMOUS CELL; COMORBIDITY; HUMANS; LUNG NEOPLASMS; MUTATION; RECEPTOR, EPIDERMAL GROWTH FACTOR; SMOKING;

EID: 84987815216     PISSN: 15560864     EISSN: 15561380     Source Type: Journal    
DOI: 10.1016/j.jtho.2016.05.024     Document Type: Review

References (110)

1. Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87-108.
2. Siegel R, Ma J, Zou Z, et al. Cancer statistics, 2014. CA Cancer J Clin. 2014;64:9-29.
3. Villaruz LC, Burns TF, Ramfidis VS, et al. Personalizing therapy in advanced non-small cell lung cancer. Semin Respir Crit Care Med. 2013;34:822-836.
4. Travis WD, Brambilla E, Noguchi M, et al. International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol. 2011;6:244-285.
5. Zugazagoitia J, Enguita AB, Nuñez JA, et al. The new IASLC/ATS/ERS lung adenocarcinoma classification from a clinical perspective: current concepts and future prospects. J Thorac Dis. 2014;6(suppl 5):S526-S536.
6. Oliver TG, Patel J, Akerley W. Squamous non-small cell lung cancer as a distinct clinical entity. Am J Clin Oncol. 2015;38:220-226.
7. Morgensztern D, Waqar S, Subramanian J, et al. Improving survival for stage IV non-small cell lung cancer: A surveillance, epidemiology, and end results survey from 1990 to 2005. J Thorac Oncol. 2009;4: 1524-1529.
8. Cetin K, Ettinger DS, Hei YJ, et al. Survival by histologic subtype in stage IV nonsmall cell lung cancer based on data from the Surveillance, Epidemiology and End Results Program. Clin Epidemiol. 2011;3:139-148.
9. Hirsch FR, Spreafico A, Novello S, et al. The prognostic and predictive role of histology in advanced non-small cell lung cancer: A literature review. J Thorac Oncol. 2008;3:1468-1481.
10. Paz-Ares LG, de Marinis F, Dediu M, et al. PARAMOUNT: Final overall survival results of the phase III study of maintenance pemetrexed versus placebo immediately after induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer. J Clin Oncol. 2013;31:2895-2902.
11. Sandler A, Gray R, Perry MC, et al. Paclitaxelcarboplatin alone or with bevacizumab for non-smallcell lung cancer. N Engl J Med. 2006;355:2542-2550.
12. Scagliotti G, Novello S, von Pawel J, et al. Phase III study of carboplatin and paclitaxel alone or with sorafenib in advanced non-small-cell lung cancer. J Clin Oncol. 2010;28:1835-1842.
13. 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. 2008;26:3543-3551.
14. Socinski MA, Bondarenko I, Karaseva NA, et al. Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. J Clin Oncol. 2012;30:2055-2062.
15. Travis WD, Brambilla E, Nicholson AG, et al. The 2015 World Health Organization Classification of Lung Tumors: impact of genetic, clinical and radiologic advances since the 2004 classification. J Thorac Oncol. 2015;10:1243-1260.
16. Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG, eds. WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart. 4th ed. Lyon, France: IARC Press; 2015.
17. Thunnissen E, Kerr KM, Herth FJF, et al. The challenge of NSCLC diagnosis and predictive analysis on small samples. Practical approach of a working group. Lung Cancer. 2012;76:1-18.
18. Terry J, Leung S, Laskin J, et al. Optimal immunohistochemical markers for distinguishing lung adenocarcinomas from squamous cell carcinomas in small tumor samples. Am J Surg Pathol. 2010;34:1805-1811.
19. Hallack Neto AE, Siqueira SAC, Dulley FL, et al. p63 protein expression in high risk diffuse large B-cell lymphoma. J Clin Pathol. 2009;62:77-79.
20. Bishop JA, Teruya-Feldstein J, Westra WH, et al. p40 (dNp63) is superior to p63 for the diagnosis of pulmonary squamous cell carcinoma. Mod Pathol. 2012;25: 405-415.
21. Loo PS, Thomas SC, Nicolson MC, et al. Subtyping of undifferentiated non-small cell carcinomas in bronchial biopsy specimens. J Thorac Oncol. 2010;5:442-447.
22. Gruver AM, Amin MB, Luthringer DJ, et al. Selective immunohistochemical markers to distinguish between metastatic high-grade urothelial carcinoma and primary poorly differentiated invasive squamous cell carcinoma of the lung. Arch Pathol Lab Med. 2012;136:1339-1346.
23. Rosado-de-Christenson ML, Templeton PA, Moran CA. Bronchogenic carcinoma: Radiologic-pathologic correlation. Radiographics. 1994;14:429-446.
24. Gill RR, Matsusoka S, Hatabu H. Cavities in the lung in oncology patients: imaging overview and differential diagnoses. Applied Radiology. 2010;39:10-21.
25. Nichols L, Saunders R, Knollmann FD. Causes of death of patients with lung cancer. Arch Pathol Lab Med. 2012;136:1552-1557.
26. Wilson DO, Ryan A, Fuhrman C, et al. Doubling times and CT screen-detected lung cancers in the Pittsburgh Lung Screening Study. Am J Respir Crit Care Med. 2012;185:85-89.
27. Ito M, Niho S, Nihei K, et al. Risk factors associated with fatal pulmonary hemorrhage in locally advanced nonsmall cell lung cancer treated with chemoradiotherapy. BMC Cancer. 2012;12:27.
28. Dela Cruz CS, Tanoue LT, Matthay RA. Lung cancer: Epidemiology, etiology, and prevention. Clin Chest Med. 2011;32:605-644.
29. Peto R, Darby S, Deo H, et al. Smoking, smoking cessation, and lung cancer in the UK since 1950: combination of national statistics with two case-control studies. BMJ. 2000;321:323-329.
30. Duarte RL, Luiz RR, Paschoal ME. The cigarette burden (measured by the number of pack-years smoked) negatively impacts the response rate to platinum-based chemotherapy in lung cancer patients. Lung Cancer. 2008;61:244-254.
31. Fox JL, Rosenzweig KE, Ostroff JS. The effect of smoking status on survival following radiation therapy for non-small cell lung cancer. Lung Cancer. 2004;44:287-293.
32. Hughes AN, O'Brien ME, Petty WJ, et al. Overcoming CYP1A1/1A2 mediated induction of metabolism by escalating erlotinib dose in current smokers. J Clin Oncol. 2009;27:1220-1226.
33. Parsons A, Daley A, Begh R, et al. Influence of smoking cessation after diagnosis of early stage lung cancer on prognosis: systematic review of observational studies with meta-Analysis. BMJ. 2010;340:b5569.
34. Papi A, Casoni G, Caramori G, et al. COPD increases the risk of squamous histological subtype in smokers who develop non-small cell lung carcinoma. Thorax. 2004;59:679-681.
35. Pesch B, Kendzia B, Gustavsson P, et al. Cigarette smoking and lung cancer-relative risk estimates for the major histological types from a pooled analysis of casecontrol studies. Int J Cancer. 2012;131:1210-1219.
36. Radzikowska E, Glaz P, Roszkowski K. Lung cancer in women: Age, smoking, histology, performance status, stage, initial treatment and survival. Population-based study of 20 561 cases. Ann Oncol. 2002;13:1087-1093.
37. Carter BD, Abnet CC, Feskanich D, et al. Smoking and mortality-beyond established causes. N Engl J Med. 2015;372:631-640.
38. Youlden DR, Cramb SM, Baade PD. The International Epidemiology of Lung Cancer: geographical distribution and secular trends. J Thorac Oncol. 2008;3:819-831.
39. Schroeder SA, Warner KE. Don't forget tobacco. N Engl J Med. 2010;363:201-204.
40. The National Lung Screening Trial Research Team. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365:395-409.
41. Moyer VA, U.S. Preventative Services Task Force. Screening for lung cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2014;160:330-338.
42. Pinsky PF, Church TR, Izmirlian G, et al. The National Lung Screening Trial: Results stratified by demographics, smoking history and lung cancer histology. Cancer. 2013;119:3976-3983.
43. Frauenfelder T, Puhan MA, Lazor R, et al. Early detection of lung cancer: A statement from an expert panel of the Swiss university hospitals on lung cancer screening. Respiration. 2014;87:254-264.
44. Prosch H, Schaefer-Prokop C. Screening for lung cancer. Curr Opin Oncol. 2014;26:131-137.
45. Devesa SS, Bray F, Vizcaino AP, et al. International lung cancer trends by histologic type: male:female differences diminishing and adenocarcinoma rates rising. Int J Cancer. 2005;117:294-299.
46. D'Addario G, Früh M, Reck M, et al. Metastatic nonsmall- cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21(suppl 5):v116-v119.
47. Houston KA, Henley SJ, Li J, et al. Patterns in lung cancer incidence rates and trends by histologic type in the United States, 2004-2009. Lung Cancer. 2014;86: 22-28.
48. Sakurai H, Asamura H, Goya T, et al. Survival differences by gender for resected non-small cell lung cancer: A retrospective analysis of 12, 509 cases in a Japanese Lung Cancer Registry study. J Thorac Oncol. 2010;5:1594-1601.
49. Visbal AL, Williams BA, Nichols FC III, et al. Gender differences in non-small-cell lung cancer survival: An analysis of 4, 618 patients diagnosed between 1997 and 2002. Ann Thorac Surg. 2004;78:209-215.
50. National Cancer Institute. SEER cancer statistics factsheets: lung and bronchus cancer. http://seer.cancer.gov/statfacts/html/lungb.html. Accessed December 8, 2015.
51. National Cancer Institute. SEER cancer statistics review, 1975-2012. http://seer.cancer.gov/csr/1975-2012/. Accessed December 8, 2015.
52. Nadpara PA, Madhavan SS, Tworek C, et al. Guidelineconcordant lung cancer care and associated health outcomes among elderly patients in the United States. J Geriatr Oncol. 2015;6:101-110.
53. Aarts MJ, van den Borne BE, Biesma B, et al. Improvement in population-based survival of stage IV NSCLC due to increased use of chemotherapy. Int J Cancer. 2015;136:E387-E395.
54. Janssen-Heijnen ML, Schipper RM, Razenberg PP, et al. Prevalence of co-morbidity in lung cancer patients and its relationship with treatment: A population-based study. Lung Cancer. 1998;21:105-113.
55. Grønberg BH, Sundstrøm S, Kaasa S, et al. Influence of comorbidity on survival, toxicity and health-related quality of life in patients with advanced non-small-cell lung cancer receiving platinum-doublet chemotherapy. Eur J Cancer. 2010;46:2225-2234.
56. Asmis TR, Ding K, Seymour L, et al. Age and comorbidity as independent prognostic factors in the treatment of non small-cell lung cancer: A review of National Cancer Institute of Canada Clinical Trials Group trials. J Clin Oncol. 2008;26:54-59.
57. Jørgensen TL, Hallas J, Friis S, et al. Comorbidity in elderly cancer patients in relation to overall and cancer-specific mortality. Br J Cancer. 2012;106: 1353-1360.
58. Lee PN, Forey BA. Indirectly estimated absolute lung cancer mortality rates by smoking status and histological type based on a systematic review. BMC Cancer. 2013;13:189.
59. Søgaard M, Thomsen RW, Bossen KS, et al. The impact of comorbidity on cancer survival: A review. Clin Epidemiol. 2013;5(suppl 1):3-29.
60. Rosell R, Carcereny E, Gervais R, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): A multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012;13:239-246.
61. Maemondo M, Inoue A, Kobayashi K, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010;362:2380-2388.
62. Shaw AT, Kim DW, Nakagawa K, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013;368:2385-2394.
63. Wang J, Shen Q, Shi Q, et al. Detection of ALK protein expression in lung squamous cell carcinomas by immunohistochemistry. J Exp Clin Cancer Res. 2014;33:109.
64. Forbes SA, Bhamra G, Bamford S, et al. The Catalogue of Somatic Mutations in Cancer (COSMIC). Curr Protoc Hum Genet. 2008 Chapter 10:Unit 10.11.
65. Caliò A, Nottegar A, Gilioli E, et al. ALK/EML4 fusion gene may be found in pure squamous carcinoma of the lung. J Thorac Oncol. 2014;9:729-732.
66. Rekhtman N, Paik PK, Arcila ME, et al. Clarifying the spectrum of driver oncogene mutations in biomarkerverified squamous carcinoma of lung: lack of EGFR/KRAS and presence of PIK3CA/AKT1 mutations. Clin Cancer Res. 2012;18:1167-1176.
67. Liao RG, Watanabe H, Meyerson M, et al. Targeted therapy for squamous cell lung cancer. Lung Cancer Manag. 2012;1:293-300.
68. Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol. 2011;12:175-180.
69. Cancer Genome Atlas Research Network. Comprehensive genomic characterization of squamous cell lung cancers. Nature. 2012;489:519-525.
70. Kim Y, Hammerman PS, Kim J, et al. Integrative and comparative genomic analysis of lung squamous cell carcinomas in East Asian patients. J Clin Oncol. 2014;32:121-128.
71. Hirsch FR, Varella-Garcia M, Bunn PA Jr, et al. Epidermal growth factor receptor in non-small-cell lung carcinomas: correlation between gene copy number and protein expression and impact on prognosis. J Clin Oncol. 2003;21:3798-3807.
72. Pirker R, Pereira JR, von Pawel J, et al. EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer: Analysis of data from the phase 3 FLEX study. Lancet Oncol. 2012;13:33-42.
73. Thatcher N, Hirsch FR, Luft AV, et al. Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): An open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2015;16:763-774.
74. Pirker R, Pereira JR, Szczesna A, et al. Prognostic factors in patients with advanced non-small cell lung cancer: data from the phase III FLEX study. Lung Cancer. 2012;77:376-382.
75. Young NR, Soneru C, Liu J, et al. Afatinib efficacy against squamous cell carcinoma of the head and neck cell lines in vitro and in vivo. Target Oncol. 2015;10:501-508.
76. Dutt A, Ramos AH, Hammerman PS, et al. Inhibitorsensitive FGFR1 amplification in human non-small cell lung cancer. PLoS One. 2011;6:e20351.
77. Heist RS, Mino-Kenudson M, Sequist LV, et al. FGFR1 amplification in squamous cell carcinoma of the lung. J Thorac Oncol. 2012;7:1775-1780.
78. Gadgeel SM, Chen W, Cote ML, et al. Fibroblast growth factor receptor 1 amplification in non-small cell lung cancer by quantitative real-Time PCR. PLoS One. 2013;8:e79820.
79. Sos ML, Thomas RK. Genetic insight and therapeutic targets in squamous-cell lung cancer. Oncogene. 2012;31:4811-4814.
80. Weiss J, Sos ML, Seidel D, et al. Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous-cell lung cancer. Sci Transl Med. 2010;2:62ra93.
81. Paik PK, Shen R, Ferry D, et al. A phase 1b openlabel multicenter study of AZD4547 in patients with advanced squamous cell lung cancers: Preliminary antitumour activity and pharmacodynamic data [abstract]. J Clin Oncol. 2014;32(suppl 5):8035.
82. Nogova L, Sequist LV, Cassier PA, et al. Targeting FGFR1-Amplified lung squamous cell carcinoma with the selective pan-FGFR inhibitor BGJ398 [abstract]. J Clin Oncol. 2014;32(suppl 5):8034.
83. Wynes MW, Hinz TK, Gao D, et al. FGFR1 mRNA and protein expression, not gene copy number, predict FGFR TKI sensitivity across all lung cancer histologies. Clin Cancer Res. 2014;20:3299-3309.
84. Okudela K, Suzuki M, Kageyama S, et al. PIK3CA mutation and amplification in human lung cancer. Pathol Int. 2007;57:664-671.
85. Heist RS, Sequist LV, Engelman JA. Genetic changes in squamous cell lung cancer: A review. J Thorac Oncol. 2012;7:924-933.
86. Vansteenkiste JF, Canon JL, De Braud F, et al. Safety and efficacy of buparlisib (BKM120) in patients with PI3K pathway-Activated non-small cell lung cancer: Results from the phase II BASALT-1 study. J Thorac Oncol. 2015;10:1319-1327.
87. Hammerman PS, Sos ML, Ramos AH, et al. Mutations in the DDR2 kinase gene identify a novel therapeutic target in squamous cell lung cancer. Cancer Discov. 2011;1:78-89.
88. Miao L, Wang Y, Zhu S, et al. Identification of novel driver mutations of the discoidin domain receptor 2 (DDR2) gene in squamous cell lung cancer of Chinese patients. BMC Cancer. 2014;14:369.
89. Brunner AM, Costa DB, Heist RS, et al. Treatmentrelated toxicities in a phase II trial of dasatinib in patients with squamous cell carcinoma of the lung. J Thorac Oncol. 2013;8:1434-1437.
90. Clinical trial NCT01514864. https://clinicaltrials.gov/ct2/show/NCT01514864?term=NCT01514864&rank=1. Accessed April 27, 2016.
91. Shibata T, Saito S, Kokubu A, et al. Global downstream pathway analysis reveals a dependence of oncogenic NF-E2-related factor 2 mutation on the mTOR growth signaling pathway. Cancer Res. 2010;70:9095-9105.
92. Kim SH, Lee S, Lee CH, et al. Expression of cancer-Testis antigens MAGE-A3/6 and NY-ESO-1 in non-small-cell lung carcinomas and their relationship with immune cell infiltration. Lung. 2009;187:401-411.
93. Vansteenkiste J, Cho BC, Vanakesa T, et al. MAGRIT, a double-blind, randomized, placebo-controlled phase III study to assess the efficacy of the recMAGE-A3 AS15 cancer immunotherapeutic as adjuvant therapy in patients with resected MAGE-A3-positive non-small cell lung cancer (NSCLC). Abstract 1173O presented at the 2014 European Society Medical Oncology Congress. September 26-30, 2014; Madrid, Spain.
94. Ikeda S, Funakoshi N, Inagaki M, et al. Clinicopathologic roles of tumor-infiltrating lymphocytes and CD8-positive lymphocytes in lung cancer imprint smears in squamous cell carcinoma and adenocarcinoma. Acta Cytol. 2006;50:423-429.
95. Yoshida N, Abe H, Ohkuri T, et al. Expression of the MAGE-A4 and NY-ESO-1 cancer-Testis antigens and T cell infiltration in non-small cell lung carcinoma and their prognostic significance. Int J Oncol. 2006;28:1089-1098.
96. da Costa Souza P, Parra ER, Atanazio MJ, et al. Different morphology, stage and treatment affect immune cell infiltration and long-Term outcome in patients with non-small-cell lung carcinoma. Histopathology. 2012; 61:587-596.
97. Kitazono S, Fujiwara Y, Tsuta K, et al. Reliability of small biopsy samples compared with resected specimens for the determination of programmed death-ligand 1 expression in non-small-cell lung cancer. Clin Lung Cancer. 2015;16:385-390.
98. Velcheti V, Schalper KA, Carvajal DE, et al. Programmed death ligand-1 expression in non-small cell lung cancer. Lab Invest. 2014;94:107-116.
99. D'Incecco A, Andreozzi M, Ludovini V, et al. PD-1 and PD-L1 expression in molecularly selected non-smallcell lung cancer patients. Br J Cancer. 2015;112: 95-102.
100. Rebelatto M, Mistry A, Sabalos C, et al. Development of a PD-L1 companion diagnostic assay for treatment with MEDI4736 in NSCLC and SCCHN patients [abstract]. J Clin Oncol. 2015;3(suppl):8033.
101. Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366:2443-2454.
102. 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. 2015;348:124-128.
103. US Food and Drug Administration. Keytruda. Highlights of prescribing information. http://www.accessdata.fda.gov/drugsatfda-docs/label/2015/125514s004s006lbl.pdf. Accessed April 18, 2016.
104. US Food and Drug Administration. Opdivo. Highlights of prescribing information. http://www.accessdata.fda.gov/drugsatfda-docs/label/2015/125554s005lbl.pdf. Accessed October 22, 2015.
105. Clinical trial NCT02409355. https://clinicaltrials.gov/ct2/show/NCT02409355. Accessed April 27, 2016.
106. Clinical trial NCT02367794. https://clinicaltrials.gov/ct2/show/NCT02367794. Accessed April 27, 2016.
107. Clinical trial NCT02041533. https://clinicaltrials.gov/ct2/show/NCT02041533. Accessed April 27, 2016.
108. Brahmer JR, Kim ES, Zhang J, et al. KEYNOTE-024: phase III trial of pembrolizumab (MK-3475) vs platinumbased chemotherapy as first-line therapy for patients with metastatic non-small cell lung cancer (NSCLC) that expresses programmed cell death ligand 1 (PD-L1) [abstract]. J Clin Oncol. 2015;33(suppl):TPS8103.
109. Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361:947-957.
110. Kwak EL, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010;363:1693-1703.