1932

Abstract

Lung cancer is the leading cause of cancer death in the United States and many other parts of the world. Non–small cell lung cancer (NSCLC) comprises 85–90% of lung cancers. Historically, the expected survival of patients with advanced disease has been estimated in months. In recent years, however, lung cancer has come to be seen as a treatable disease with multiple therapeutic options. Enormous advances in the understanding of its pathways and mechanisms have enabled personalized therapy in NSCLC. The evolving approach to therapy focuses on genomic profiling of the tumors to find molecular targets and develop specific agents for individualized therapy. In addition, maintenance therapy has emerged as a valid approach, and the choice of chemotherapy now varies by histology. Most recently, immunotherapy with checkpoint inhibitors has shown promising results, with impressive durations of response and a tolerable toxicity profile. Together, these discoveries have improved overall survival substantially in patient populations that have access to these advancements. We review the clinical data surrounding these impressive improvements.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-med-042915-102442
2017-01-14
2024-04-21
Loading full text...

Full text loading...

/deliver/fulltext/med/68/1/annurev-med-042915-102442.html?itemId=/content/journals/10.1146/annurev-med-042915-102442&mimeType=html&fmt=ahah

Literature Cited

  1. Siegel R, Ma J, Zou Z. 1.  et al. 2014. Cancer statistics, 2014. CA: Cancer J. Clin. 64:9–29 [Google Scholar]
  2. Haiman CA, Stram DO, Wilkens LR. 2.  et al. 2006. Ethnic and racial differences in the smoking-related risk of lung cancer. N. Engl. J. Med. 354:333–42 [Google Scholar]
  3. Meza R, Meernik C, Jeon J. 3.  et al. 2015. Lung cancer incidence trends by gender, race and histology in the United States, 1973–2010. PLOS ONE 10:e0121323 [Google Scholar]
  4. Aberle DR, Adams AM. 4. National Lung Screening Trial Research Team, et al. 2011. Reduced lung-cancer mortality with low-dose computed tomographic screening. N. Engl. J. Med. 365:395–409 [Google Scholar]
  5. Johnson DH, Fehrenbacher L, Novotny WF. 5.  et al. 2004. Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J. Clin. Oncol. 22:2184–91 [Google Scholar]
  6. Lynch TJ, Bell DW, Sordella R. 6.  et al. 2004. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N. Engl. J. Med. 350:2129–39 [Google Scholar]
  7. Kwak EL, Bang YJ, Camidge DR. 7.  et al. 2010. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N. Engl. J. Med. 363:1693–703 [Google Scholar]
  8. Rapp E, Pater JL, Willan A. 8.  et al. 1988. Chemotherapy can prolong survival in patients with advanced non-small-cell lung cancer—report of a Canadian multicenter randomized trial. J. Clin. Oncol. 6:633–41 [Google Scholar]
  9. Rosell R, Gatzemeier U, Betticher DC. 9.  et al. 2002. Phase III randomised trial comparing paclitaxel/carboplatin with paclitaxel/cisplatin in patients with advanced non-small-cell lung cancer: a cooperative multinational trial. Ann. Oncol. 13:1539–49 [Google Scholar]
  10. Fossella F, Pereira JR, von Pawel J. 10.  et al. 2003. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer. The TAX 326 Study Group. J. Clin. Oncol. 21:3016–24 [Google Scholar]
  11. Kelly K, Crowley J, Bunn PA Jr.. 11.  et al. 2001. 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. 19:3210–18 [Google Scholar]
  12. Wozniak AJ, Crowley JJ, Balcerzak SP. 12.  et al. 1998. Randomized trial comparing cisplatin with cisplatin plus vinorelbine in the treatment of advanced non-small-cell lung cancer: a Southwest Oncology Group study. J. Clin. Oncol. 16:2459–65 [Google Scholar]
  13. Sandler AB, Nemunaitis J, Denham C. 13.  et al. 2000. Phase III trial of gemcitabine plus cisplatin versus cisplatin alone in patients with locally advanced or metastatic non-small-cell lung cancer. J. Clin. Oncol. 18:122–30 [Google Scholar]
  14. Lilenbaum RC, Herndon JE 2nd, List MA. 14.  et al. 2005. Single-agent versus combination chemotherapy in advanced non-small-cell lung cancer. The Cancer and Leukemia Group B (Study 9730). J. Clin. Oncol. 23:190–6 [Google Scholar]
  15. Delbaldo C, Michiels S, Syz N. 15.  et al. 2004. Benefits of adding a drug to a single-agent or a 2-agent chemotherapy regimen in advanced non-small-cell lung cancer: a meta-analysis. JAMA 292:470–84 [Google Scholar]
  16. Comella P, Filippelli G, De Cataldis G. 16.  et al. 2007. Efficacy of the combination of cisplatin with either gemcitabine and vinorelbine or gemcitabine and paclitaxel in the treatment of locally advanced or metastatic non-small-cell lung cancer: a phase III randomised trial of the Southern Italy Cooperative Oncology Group (SICOG 0101). Ann. Oncol. 18:324–30 [Google Scholar]
  17. Alberola V, Camps C, Provencio M. 17.  et al. 2003. Cisplatin plus gemcitabine versus a cisplatin-based triplet versus nonplatinum sequential doublets in advanced non-small-cell lung cancer: a Spanish Lung Cancer Group phase III randomized trial. J. Clin. Oncol. 21:3207–13 [Google Scholar]
  18. Sandler A, Gray R, Perry MC. 18.  et al. 2006. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N. Engl. J. Med. 355:2542–50 [Google Scholar]
  19. Garon EB, Ciuleanu TE, Arrieta O. 19.  et al. 2014. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet 384:665–73 [Google Scholar]
  20. Fidias PM, Dakhil SR, Lyss AP. 20.  et al. 2009. Phase III study of immediate compared with delayed docetaxel after front-line therapy with gemcitabine plus carboplatin in advanced non-small-cell lung cancer. J. Clin. Oncol. 27:591–98 [Google Scholar]
  21. Ciuleanu T, Brodowicz T, Zielinski C. 21.  et al. 2009. 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 374:1432–40 [Google Scholar]
  22. Cappuzzo F, Ciuleanu T, Stelmakh L. 22.  et al. 2010. Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol 11:521–29 [Google Scholar]
  23. Soria JC, Felip E, Cobo M. 23.  et al. 2015. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial. Lancet Oncol 16:897–907 [Google Scholar]
  24. Paz-Ares L, de Marinis F, Dediu M. 24.  et al. 2012. Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial. Lancet Oncol 13:247–55 [Google Scholar]
  25. Paz-Ares LG, de Marinis F, Dediu M. 25.  et al. 2013. 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. 31:2895–902 [Google Scholar]
  26. Patel JD, Socinski MA, Garon EB. 26.  et al. 2013. PointBreak: a randomized phase III study of pemetrexed plus carboplatin and bevacizumab followed by maintenance pemetrexed and bevacizumab versus paclitaxel plus carboplatin and bevacizumab followed by maintenance bevacizumab in patients with stage IIIB or IV nonsquamous non-small-cell lung cancer. J. Clin. Oncol. 31:4349–57 [Google Scholar]
  27. Barlesi F, Scherpereel A, Rittmeyer A. 27.  et al. 2013. Randomized phase III trial of maintenance bevacizumab with or without pemetrexed after first-line induction with bevacizumab, cisplatin, and pemetrexed in advanced nonsquamous non-small-cell lung cancer: AVAPERL (MO22089). J. Clin. Oncol. 31:3004–11 [Google Scholar]
  28. Zinner RG, Obasaju CK, Spigel DR. 28.  et al. 2015. PRONOUNCE: randomized, open-label, phase III study of first-line pemetrexed + carboplatin followed by maintenance pemetrexed versus paclitaxel + carboplatin + bevacizumab followed by maintenance bevacizumab in patients with advanced nonsquamous non-small-cell lung cancer. J. Thorac. Oncol. 10:134–42 [Google Scholar]
  29. Ettinger DS, Wood DE, Akerley W. 29.  et al. 2014. Non-small cell lung cancer, version 1.2015. J. Natl. Compr. Cancer Netw 12:1738–61 [Google Scholar]
  30. Berge EM, Doebele RC. 30.  2014. Targeted therapies in non-small cell lung cancer: emerging oncogene targets following the success of epidermal growth factor receptor. Semin. Oncol. 41:110–25 [Google Scholar]
  31. Doebele RC, Pilling AB, Aisner DL. 31.  et al. 2012. Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non-small cell lung cancer. Clin. Cancer Res. 18:1472–82 [Google Scholar]
  32. Kris MG, Johnson BE, Berry LD. 32.  et al. 2014. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA 311:1998–2006 [Google Scholar]
  33. Leighl NB, Rekhtman N, Biermann WA. 33.  et al. 2014. Molecular testing for selection of patients with lung cancer for epidermal growth factor receptor and anaplastic lymphoma kinase tyrosine kinase inhibitors: American Society of Clinical Oncology endorsement of the College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology guideline. J. Clin. Oncol. 32:3673–79 [Google Scholar]
  34. Sharma SV, Bell DW, Settleman J. 34.  et al. 2007. Epidermal growth factor receptor mutations in lung cancer. Nat. Rev. Cancer 7:169–81 [Google Scholar]
  35. Paez JG, Janne PA, Lee JC. 35.  et al. 2004. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304:1497–500 [Google Scholar]
  36. Pao W, Miller V, Zakowski M. 36.  et al. 2004. EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib. PNAS 101:13306–11 [Google Scholar]
  37. Steuer CE, Behera M, Berry L. 37.  et al. 2016. Role of race in oncogenic driver prevalence and outcomes in lung adenocarcinoma: results from the Lung Cancer Mutation Consortium. Cancer 122:766–72 [Google Scholar]
  38. Sordella R, Bell DW, Haber DA. 38.  et al. 2004. Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways. Science 305:1163–67 [Google Scholar]
  39. Thatcher N, Chang A, Parikh P. 39.  et al. 2005. 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 366:1527–37 [Google Scholar]
  40. Shepherd FA, Rodrigues Pereira J, Ciuleanu T. 40.  et al. 2005. Erlotinib in previously treated non-small-cell lung cancer. N. Engl. J. Med. 353:123–32 [Google Scholar]
  41. Mok TS, Wu YL, Thongprasert S. 41.  et al. 2009. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N. Engl. J. Med. 361:947–57 [Google Scholar]
  42. Maemondo M, Inoue A, Kobayashi K. 42.  et al. 2010. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N. Engl. J. Med. 362:2380–88 [Google Scholar]
  43. Zhou C, Wu YL, Chen G. 43.  et al. 2011. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol 12:735–42 [Google Scholar]
  44. Sequist LV, Yang JC, Yamamoto N. 44.  et al. 2013. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J. Clin. Oncol. 31:3327–34 [Google Scholar]
  45. Yang JC, Wu YL, Schuler M. 45.  et al. 2015. 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 16:141–51 [Google Scholar]
  46. Janne PA, Wang X, Socinski MA. 46.  et al. 2012. Randomized phase II trial of erlotinib alone or with carboplatin and paclitaxel in patients who were never or light former smokers with advanced lung adenocarcinoma: CALGB 30406 trial. J. Clin. Oncol. 30:2063–69 [Google Scholar]
  47. Gridelli C, Ciardiello F, Gallo C. 47.  et al. 2012. First-line erlotinib followed by second-line cisplatin-gemcitabine chemotherapy in advanced non-small-cell lung cancer: the TORCH randomized trial. J. Clin. Oncol. 30:3002–11 [Google Scholar]
  48. Yu HA, Arcila ME, Rekhtman N. 48.  et al. 2013. Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers. Clin. Cancer Res. 19:2240–47 [Google Scholar]
  49. Kumar M, Ernani V, Owonikoko TK. 49.  2015. Biomarkers and targeted systemic therapies in advanced non-small cell lung cancer. Mol. Aspects Med. 45:55–66 [Google Scholar]
  50. Janne PA, Yang JC, Kim DW. 50.  et al. 2015. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. N. Engl. J. Med. 372:1689–99 [Google Scholar]
  51. Sequist LV, Rolfe L, Allen AR. 51.  2015. Rociletinib in EGFR-mutated non-small-cell lung cancer. N. Engl. J. Med. 373:578–79 [Google Scholar]
  52. Sacher AG, Paweletz C, Dahlberg SE. 52.  et al. 2016. Prospective validation of rapid plasma genotyping for the detection of EGFR and KRAS mutations in advanced lung cancer. JAMA Oncol 2:1014–22 [Google Scholar]
  53. Shaw AT, Yeap BY, Mino-Kenudson M. 53.  et al. 2009. Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK. J. Clin. Oncol. 27:4247–53 [Google Scholar]
  54. Ou SH, Kwak EL, Siwak-Tapp C. 54.  et al. 2011. Activity of crizotinib (PF02341066), a dual mesenchymal-epithelial transition (MET) and anaplastic lymphoma kinase (ALK) inhibitor, in a non-small cell lung cancer patient with de novo MET amplification. J. Thorac. Oncol. 6:942–46 [Google Scholar]
  55. Bergethon K, Shaw AT, Ou SH. 55.  et al. 2012. ROS1 rearrangements define a unique molecular class of lung cancers. J. Clin. Oncol. 30:863–70 [Google Scholar]
  56. Shaw AT, Kim DW, Nakagawa K. 56.  et al. 2013. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N. Engl. J. Med. 368:2385–94 [Google Scholar]
  57. Solomon BJ, Mok T, Kim DW. 57.  et al. 2014. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N. Engl. J. Med. 371:2167–77 [Google Scholar]
  58. Shaw AT, Engelman JA. 58.  2014. Ceritinib in ALK-rearranged non-small-cell lung cancer. N. Engl. J. Med. 370:2537–39 [Google Scholar]
  59. Shaw AT, Gandhi L, Gadgeel S. 59.  et al. 2016. Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: a single-group, multicentre, phase 2 trial. Lancet Oncol 17:234–42 [Google Scholar]
  60. Rangachari D, Yamaguchi N, VanderLaan PA. 60.  et al. 2015. Brain metastases in patients with EGFR-mutated or ALK-rearranged non-small-cell lung cancers. Lung Cancer 88:108–11 [Google Scholar]
  61. Kim DW, Mehra R, Tan DS. 61.  et al. 2016. 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 17:452–63 [Google Scholar]
  62. Gainor JF, Shaw AT. 62.  2013. Novel targets in non-small cell lung cancer: ROS1 and RET fusions. Oncologist 18:865–75 [Google Scholar]
  63. Shaw AT, Ou SH, Bang YJ. 63.  et al. 2014. Crizotinib in ROS1-rearranged non-small-cell lung cancer. N. Engl. J. Med. 371:1963–71 [Google Scholar]
  64. Slebos RJ, Hruban RH, Dalesio O. 64.  et al. 1991. Relationship between K-ras oncogene activation and smoking in adenocarcinoma of the human lung. J. Natl. Cancer Inst. 83:1024–27 [Google Scholar]
  65. Slebos RJ, Kibbelaar RE, Dalesio O. 65.  et al. 1990. K-ras oncogene activation as a prognostic marker in adenocarcinoma of the lung. N. Engl. J. Med. 323:561–65 [Google Scholar]
  66. Eberhard DA, Johnson BE, Amler LC. 66.  et al. 2005. Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. J. Clin. Oncol. 23:5900–9 [Google Scholar]
  67. Sadiq AA, Salgia R. 67.  2013. MET as a possible target for non-small-cell lung cancer. J. Clin. Oncol. 31:1089–96 [Google Scholar]
  68. Olivero M, Rizzo M, Madeddu R. 68.  et al. 1996. Overexpression and activation of hepatocyte growth factor/scatter factor in human non-small-cell lung carcinomas. Br. J. Cancer 74:1862–68 [Google Scholar]
  69. Nakamura Y, Niki T, Goto A. 69.  et al. 2007. c-Met activation in lung adenocarcinoma tissues: an immunohistochemical analysis. Cancer Sci 98:1006–13 [Google Scholar]
  70. Beau-Faller M, Ruppert AM, Voegeli AC. 70.  et al. 2008. MET gene copy number in non-small cell lung cancer: molecular analysis in a targeted tyrosine kinase inhibitor naive cohort. J. Thorac. Oncol. 3:331–39 [Google Scholar]
  71. Onozato R, Kosaka T, Kuwano H. 71.  et al. 2009. Activation of MET by gene amplification or by splice mutations deleting the juxtamembrane domain in primary resected lung cancers. J. Thorac. Oncol. 4:5–11 [Google Scholar]
  72. Ma PC, Jagadeeswaran R, Jagadeesh S. 72.  et al. 2005. Functional expression and mutations of c-Met and its therapeutic inhibition with SU11274 and small interfering RNA in non-small cell lung cancer. Cancer Res 65:1479–88 [Google Scholar]
  73. Awad MM, Oxnard GR, Jackman DM. 73.  et al. 2016. MET exon 14 mutations in non-small-cell lung cancer are associated with advanced age and stage-dependent MET genomic amplification and c-Met overexpression. J. Clin. Oncol. 34:721–30 [Google Scholar]
  74. Paik PK, Drilon A, Fan PD, Yu H, Rekhtman N. 74.  et al. 2015. Response to MET inhibitors in patients with stage IV lung adenocarcinomas harboring MET mutations causing exon 14 skipping. Cancer Discov 5:842–49 [Google Scholar]
  75. Ju YS, Lee WC, Shin JY. 75.  et al. 2012. A transforming KIF5B and RET gene fusion in lung adenocarcinoma revealed from whole-genome and transcriptome sequencing. Genome Res 22:436–45 [Google Scholar]
  76. Pan Y, Zhang Y, Li Y. 76.  et al. 2014. ALK, ROS1 and RET fusions in 1139 lung adenocarcinomas: a comprehensive study of common and fusion pattern-specific clinicopathologic, histologic and cytologic features. Lung Cancer 84:121–26 [Google Scholar]
  77. Lipson D, Capelletti M, Yelensky R. 77.  et al. 2012. Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies. Nat. Med. 18:382–84 [Google Scholar]
  78. Drilon A, Wang L, Hasanovic A. 78.  et al. 2013. Response to cabozantinib in patients with RET fusion-positive lung adenocarcinomas. Cancer Discov 3:630–35 [Google Scholar]
  79. Arcila ME, Chaft JE, Nafa K. 79.  et al. 2012. Prevalence, clinicopathologic associations, and molecular spectrum of ERBB2 (HER2) tyrosine kinase mutations in lung adenocarcinomas. Clin. Cancer Res. 18:4910–18 [Google Scholar]
  80. Shigematsu H, Takahashi T, Nomura M. 80.  et al. 2005. Somatic mutations of the HER2 kinase domain in lung adenocarcinomas. Cancer Res 65:1642–46 [Google Scholar]
  81. Liu L, Shao X, Gao W. 81.  et al. 2010. The role of human epidermal growth factor receptor 2 as a prognostic factor in lung cancer: a meta-analysis of published data. J. Thorac. Oncol. 5:1922–32 [Google Scholar]
  82. Mazieres J, Peters S, Lepage B. 82.  et al. 2013. Lung cancer that harbors an HER2 mutation: epidemiologic characteristics and therapeutic perspectives. J. Clin. Oncol. 31:1997–2003 [Google Scholar]
  83. Curtin JA, Fridlyand J, Kageshita T. 83.  et al. 2005. Distinct sets of genetic alterations in melanoma. N. Engl. J. Med. 353:2135–47 [Google Scholar]
  84. Kimura ET, Nikiforova MN, Zhu Z. 84.  et al. 2003. High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma. Cancer Res 63:1454–57 [Google Scholar]
  85. Samowitz WS, Sweeney C, Herrick J. 85.  et al. 2005. Poor survival associated with the BRAF V600E mutation in microsatellite-stable colon cancers. Cancer Res 65:6063–69 [Google Scholar]
  86. Paik PK, Arcila ME, Fara M. 86.  et al. 2011. Clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations. J. Clin. Oncol. 29:2046–51 [Google Scholar]
  87. Marchetti A, Felicioni L, Malatesta S. 87.  et al. 2011. Clinical features and outcome of patients with non-small-cell lung cancer harboring BRAF mutations. J. Clin. Oncol. 29:3574–79 [Google Scholar]
  88. Gautschi O, Pauli C, Strobel K. 88.  et al. 2012. A patient with BRAF V600E lung adenocarcinoma responding to vemurafenib. J. Thorac. Oncol. 7:e23–24 [Google Scholar]
  89. Rudin CM, Hong K, Streit M. 89.  2013. Molecular characterization of acquired resistance to the BRAF inhibitor dabrafenib in a patient with BRAF-mutant non-small-cell lung cancer. J. Thorac. Oncol. 8:e41–e42 [Google Scholar]
  90. Gautschi O, Milia J, Cabarrou B. 90.  et al. 2015. Targeted therapy for patients with BRAF-mutant lung cancer: results from the European EURAF cohort. J. Thorac. Oncol. 10:1451–57 [Google Scholar]
  91. Planchard D, Kim TM, Mazieres J. 91.  et al. 2016. Dabrafenib in patients with BRAF-positive advanced non-small-cell lung cancer: a single-arm, multicentre, open-label, phase 2 trial. Lancet Oncol 17:642–50 [Google Scholar]
  92. Brahmer JR, Pardoll DM. 92.  2013. Immune checkpoint inhibitors: making immunotherapy a reality for the treatment of lung cancer. Cancer Immunol. Res. 1:85–91 [Google Scholar]
  93. Brahmer J, Reckamp KL, Baas P. 93.  et al. 2015. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N. Engl. J. Med. 373:123–35 [Google Scholar]
  94. Borghaei H, Paz-Ares L, Horn L. 94.  et al. 2015. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N. Engl. J. Med. 373:1627–39 [Google Scholar]
  95. Herbst RS, Baas P, Kim DW. 95.  et al. 2015. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 387:1540–50 [Google Scholar]
  96. Garon EB, Rizvi NA, Hui R. 96.  et al. 2015. Pembrolizumab for the treatment of non-small-cell lung cancer. N. Engl. J. Med. 372:2018–28 [Google Scholar]
  97. Antonia S, Goldberg SB, Balmanoukian A. 97.  et al. 2016. Safety and antitumour activity of durvalumab plus tremelimumab in non-small cell lung cancer: a multicentre, phase 1b study. Lancet Oncol 17:299–308 [Google Scholar]
  98. Fehrenbacher L, Spira A, Ballinger M. 98.  et al. 2016. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet 387:1837–46 [Google Scholar]
  99. Rizvi NA, Mazieres J, Planchard D. 99.  et al. 2015. Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Lancet Oncol 16:257–65 [Google Scholar]
  100. Reck M, Rodríguez-Abreu D, Robinson AG. 100.  et al. for the KEYNOTE-024 Investigators 2016. Pembrolizumab versus chemotherapy for PD-L1–positive non–small-cell lung cancer. N. Engl. J. Med. 375:1823–33 [Google Scholar]
  101. Barlesi F, Park K, Ciardiello F. 101.  et al. 2016. Primary analysis from OAK, a randomized phase III study comparing atezolizumab with docetaxel in 2L/3L NSCLC. Eur. Soc. Med. Oncol. Congr., Copenhagen, Oct. 7–11, Abstr. LBA44_PR
/content/journals/10.1146/annurev-med-042915-102442
Loading
/content/journals/10.1146/annurev-med-042915-102442
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error