Skip to main content

Personalized Therapy of Non-small Cell Lung Cancer (NSCLC)

  • Chapter
  • First Online:
Book cover Lung Cancer and Personalized Medicine: Novel Therapies and Clinical Management

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 890))

Abstract

Lung cancer remains the most common cause of cancer related deaths in both men and women in the United States and non-small cell lung cancer (NSCLC) accounts for over 85 % of all lung cancers. Survival of these patients has not significantly altered in over 30 years. This chapter initially discusses the clinical presentation of lung cancer patients. Most patients diagnosed with lung cancer due to symptoms have advanced stage cancer. Once diagnosed, lung cancer patients need imaging studies to assess the stage of the disease before decisions regarding therapy are finalized. The most important prognostic factors are stage of the disease and performance status and these factors also determine therapy. The chapter subsequently discusses management of each stage of the disease and the impact of several pathologic, clinical factors in personalizing therapy for each individual patient. Transition from chemotherapy for every patient to a more personalized approach based on histology and molecular markers has occurred in the management of advanced stage NSCLC. It is expected that such a personalized approach will extend to all stages of NSCLC and will likely improve the outcomes of all NSCLC patients.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. http://www.cancer.org/research/cancerfactsstatistics/cancerfactsfigures2014/. Accessed 15 Sept 2014

  2. Chute CG, Greenberg ER, Baron J et al (1985) Presenting conditions of 1539 population-based lung cancer patients by cell type and stage in New Hampshire and Vermont. Cancer 56:2107–11

    Article  PubMed  CAS  Google Scholar 

  3. Koyi H, Hillerdal G, Brandén E (2002) A prospective study of a total material of lung cancer from a county in Sweden 1997–1999: gender, symptoms, type, stage, and smoking habits. Lung Cancer 36:9–14

    Article  PubMed  Google Scholar 

  4. Buccheri G, Ferrigno D (2004) Lung cancer: clinical presentation and specialist referral time. Eur Respir J 24:898

    Article  PubMed  CAS  Google Scholar 

  5. The National Lung Screening Trial Research Team (2011) Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 365:395–409

    Article  PubMed Central  Google Scholar 

  6. Langer C, Lilenbaum R (2004) Role of chemotherapy in patients with poor performance status and advanced non-small cell lung cancer. Semin Oncol 31(suppl 6):8–15

    Article  PubMed  CAS  Google Scholar 

  7. Aggarwal C, Langer CJ (2012) Older age, poor performance status and major comorbidities: how to treat high-risk patients with advanced nonsmall cell lung cancer. Curr Opin Oncol 24:130–6

    Article  PubMed  Google Scholar 

  8. Mountain CF (1997) Revisions in the international system for staging lung cancer. Chest 111:1710–1717

    Article  PubMed  CAS  Google Scholar 

  9. Non-small Cell Lung Cancer Collaborative Group (1995) Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomized clinical trials. BMJ 311:899–909

    Article  Google Scholar 

  10. Butts CA, Ding K, Seymour L et al (2010) Randomized phase III trial of vinorelbine plus cisplatin compared with observation in completely resected stage IB and II non-small-cell lung cancer: updated survival analysis of JBR-10. J Clin Oncol 28:29–34

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Douillard JY, Rosell R, De Lena M et al (2006) Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB–IIIA non-small cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial. Lancet Oncology 7:719–727

    Article  PubMed  CAS  Google Scholar 

  12. Strauss GM, Herndon JE, Maddaus MA et al (2008) Adjuvant paclitaxel plus carboplatin compared with observation in stage IB non–small-cell lung cancer: CALGB 9633 with the Cancer and Leukemia Group B, Radiation Therapy Oncology Group, and North Central Cancer Treatment Group Study Groups. J Clin Oncol 26:5043–5051

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Chansky K, Sculier JP, Crowley JJ et al (2009) The International Association for the Study of Lung Cancer Staging Project: prognostic factors and pathologic TNM stage in surgically managed non-small cell lung cancer. J Thorac Oncol 4(7):792–801

    Article  PubMed  Google Scholar 

  14. Fibla JJ, Cassivi SD, Brunelli A et al (2012) Re-evaluation of the prognostic value of visceral pleura invasion in stage IB non-small cell lung cancer using the prospective multicenter ACOSOG Z0030 trial data set. Lung Cancer 78(3):259–262

    Article  PubMed  Google Scholar 

  15. Schuchert MJ, Schumacher L, Kilic A et al (2011) Impact of angiolymphatic and pleural invasion on surgical outcomes for stage I non-small cell lung cancer. Ann Thorac Surg 91(4):1059–1065

    Article  PubMed  Google Scholar 

  16. Kato T, Ishikawa K, Aragaki M et al (2012) Angiolymphatic invasion exerts a strong impact on surgical outcomes for stage I lung adenocarcinoma, but not non-adenocarcinoma. Lung Cancer 77(2):394–400

    Article  PubMed  Google Scholar 

  17. Reed E (1998) Platinum-DNA adduct, nucleotide excision repair and platinum based anti-cancer chemotherapy. Cancer Treat Rev 24(5):331–344

    Article  PubMed  CAS  Google Scholar 

  18. Olaussen KA, Dunant A, Fouret P et al (2006) DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med 355(10):983–991

    Article  PubMed  CAS  Google Scholar 

  19. Friboulet L, Olaussen KA, Pignon JP et al (2013) ERCC1 isoform expression and DNA repair in non-small-cell lung cancer. N Engl J Med 368:1101–10

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Gadgeel SM, Bepler G (2013) Prognostic and predictive markers for personalized adjuvant therapy for non-small-cell lung cancer patients. Future Oncol 9:1909–21

    Article  PubMed  CAS  Google Scholar 

  21. Goss GD, O’Callaghan C, Lorimer I et al (2013) Gefitinib versus placebo in completely resected non-small-cell lung cancer: results of the NCIC CTG BR19 study. J Clin Oncol 31:3320–6

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Kelly K, Altorki N, Eberhart E et al (2014) A randomized, double-blind phase 3 trial of adjuvant erlotinib (E) versus placebo (P) following complete tumor resection with or without adjuvant chemotherapy in patients (pts) with stage IB-IIIA EGFR positive (IHC/FISH) non-small cell lung cancer (NSCLC): RADIANT results. J Clin Oncol 32: abstract 7501

    Google Scholar 

  23. Chen HY, Yu SL, Chen CH et al (2007) A five-gene signature and clinical outcome in non-small-cell lung cancer. N Engl J Med 356(1):11–20

    Article  PubMed  CAS  Google Scholar 

  24. Kratz JR, He J, Van Den Eeden SK et al (2012) A practical molecular assay to predict survival in resected non-squamous, non-small-cell lung cancer: development and international validation studies. Lancet 379(9818):823–832

    Article  PubMed  PubMed Central  Google Scholar 

  25. Scarpaci A, Mitra P, Jarrar D et al (2013) Multimodality approach to management of stage III non-small cell lung cancer. Surg Oncol Clin N Am 22:319–28

    Article  PubMed  Google Scholar 

  26. Donington JS, Pass HI (2013) Surgical approach to locally advanced non-small cell lung cancer. Cancer J 19:217–21

    Article  PubMed  Google Scholar 

  27. Albain KS, Swann RS, Rusch VW et al (2009) Radiotherapy plus chemotherapy with or without surgical resection for stage III non-small-cell lung cancer: a phase III randomised controlled trial. Lancet 374:379–86

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Scagliotti GV, Parikh P, von Pawel J et al (2008) 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 26:3543–51

    Article  PubMed  CAS  Google Scholar 

  29. Ceppi P, Volante M, Saviozzi S et al (2006) Squamous cell carcinoma of the lung compared with other histotypes shows higher messenger RNA and protein levels for thymidylate synthase. Cancer 107:1589–96

    Article  PubMed  CAS  Google Scholar 

  30. Ciuleanu T, Brodowicz T, Zielinski C 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

    Article  PubMed  CAS  Google Scholar 

  31. Paz-Ares LG, de Marinis F, Dediu M 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

    Article  PubMed  CAS  Google Scholar 

  32. Cappuzzo F, Ciuleanu T, Stelmakh L et al (2010) Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol 11:521–9

    Article  PubMed  CAS  Google Scholar 

  33. Johnson DH, Fehrenbacher L, Novotny WF 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

    Article  PubMed  CAS  Google Scholar 

  34. Sandler A, Gray R, Perry MC et al (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355:2542–50

    Article  PubMed  CAS  Google Scholar 

  35. Reck M, von Pawel J, Zatloukal P et al (2010) Overall survival with cisplatin-gemcitabine and bevacizumab or placebo as first-line therapy for nonsquamous non-small-cell lung cancer: results from a randomised phase III trial (AVAiL). Ann Oncol 21:1804–9

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Patel JD, Socinski MA, Garon EB 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

    Article  PubMed  CAS  Google Scholar 

  37. Santos E, Martin-Zanca D, Reddy EP et al (1984) Malignant activation of a K-ras oncogene in lung carcinoma but not in normal tissue of the same patient. Science 223:661–4

    Article  PubMed  CAS  Google Scholar 

  38. Karnoub AE, Weinberg RA (2008) Ras oncogenes: split personalities. Nat Rev Mol Cell Biol 9:517–31

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Mascaux C, Iannino N, Martin B et al (2005) The role of RAS oncogene in survival of patients with lung cancer: a systematic review of the literature with meta-analysis. Br J Cancer 92(1):131–139

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Shepherd FA, Bourredjem A, Brambilla E et al (2012) Prognostic and predictive effects of KRAS mutation subtype in completely resected non-small cell lung cancer (NSCLC): A LACE-bio study. ASCO Meeting Abstracts; 30(15 suppl):7007

    Google Scholar 

  41. Tejpar S, Celik I, Schlichting M et al (2012) Association of KRAS G13D tumor mutations with outcome in patients with metastatic colorectal cancer treated with first-line chemotherapy with or without cetuximab. J Clin Oncol 30(29):3570–3577

    Article  PubMed  CAS  Google Scholar 

  42. Janne PA, Shaw AT, Pereira J et al (2013) Selumetinib plus docetaxel for KRAS-mutant advanced non-small-cell lung cancer: a randomised, multicentre, placebo-controlled, phase 2 study. Lancet Oncol 14:38–47

    Article  PubMed  CAS  Google Scholar 

  43. Nagarajan L, Louie E, Tsujimoto Y et al (1986) The human c-ros gene (ROS) is located at chromosome region 6q16----6q22. Proc Natl Acad Sci U S A 83:6568–72

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Manning G, Whyte DB, Martinez R et al (2002) The protein kinase complement of the human genome. Science 298:1912–34

    Article  PubMed  CAS  Google Scholar 

  45. Acquaviva J, Wong R, Charest A (2009) The multifaceted roles of the receptor tyrosine kinase ROS in development and cancer. Biochim Biophys Acta 1795:37–52

    PubMed  CAS  Google Scholar 

  46. Takeuchi K, Soda M, Togashi Y et al (2012) RET, ROS1 and ALK fusions in lung cancer. Nat Med 18:378–81

    Article  PubMed  CAS  Google Scholar 

  47. Bergethon A, Shaw AT, Ou SH et al (2012) ROS1 rearrangements define a unique molecular class of lung cancers. J Clin Oncol 30:863–70

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Shaw AT, Camidge DR, Engelman JR et al (2012) Clinical activity of crizotinib in advanced non-small cell lung cancer (NSCLC) harboring ROS1 gene rearrangement. J Clin Oncol 30: abstract 7508

    Google Scholar 

  49. Gherardi E, Birchmeier W, Birchmeier C et al (2012) Targeting MET in cancer: rationale and progress. Nat Rev Cancer 12:89–103

    Article  PubMed  CAS  Google Scholar 

  50. Park S, Choi YL, Sung CO et al (2012) High MET copy number and MET overexpression: poor outcome in non-small cell lung cancer patients. Histol Histopathol 27:197–207

    PubMed  Google Scholar 

  51. Ma PC, Jagadeeswaran R, Jagadeesh S 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

    Article  PubMed  CAS  Google Scholar 

  52. Cappuzzo F, Marchetti A, Skokan M et al (2009) Increased MET gene copy number negatively affects survival of surgically resected non–small-cell lung cancer patients. J Clin Oncol 27:1667–74

    Article  PubMed  PubMed Central  Google Scholar 

  53. Engelman JA, Zejnullahu K, Mitsudomi T et al (2007) MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 316:1039–43

    Article  PubMed  CAS  Google Scholar 

  54. Turke AB, Zejnullahu K, Wu YL et al (2010) Preexistence and clonal selection of MET amplification in EGFR mutant NSCLC. Cancer Cell 17:77–88

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Zhang YW, Staal B, Essenburg C et al (2010) MET kinase inhibitor SGX523 synergizes with epidermal growth factor receptor inhibitor erlotinib in a hepatocyte growth factor–dependent fashion to suppress carcinoma growth. Cancer Res 70:6880–90

    Article  PubMed  CAS  Google Scholar 

  56. Liu L, Shi H, Liu Y et al (2011) Synergistic effects of foretinib with HER-targeted agents in MET and HER1- or HER2-coactivated tumor cells. Mol Cancer Ther 10:518–30

    Article  PubMed  CAS  Google Scholar 

  57. Spigel DR, Edelman MJ, O’Byrne K et al (2014) Onartuzumab plus erlotinib versus erlotinib in previously treated stage IIIb or IV NSCLC: Results from the pivotal phase III randomized, multicenter, placebo-controlled METLung (OAM4971g) global trial. J Clin Oncol 32: abstract 8000

    Google Scholar 

  58. Sequist LV, von Pawel J, Garmey EG et al (2011) Randomized phase II study of erlotinib plus tivantinib versus erlotinib plus placebo in previously treated non-small-cell lung cancer. J Clin Oncol 29:3307–15

    Article  PubMed  CAS  Google Scholar 

  59. Camidge DR, Ou, SH, Shapiro G et al (2014) Efficacy and safety of crizotinib in patients with advanced c-MET-amplified non-small cell lung cancer (NSCLC). J Clin Oncol 32: abstract 8001

    Google Scholar 

  60. Gordon MS, Vogelzang NJ, Schoffski P et al (2011) Activity of cabozantinib (XL184) in soft tissue and bone: Results of a phase II randomized phase II discontinuation trial in patients with advanced solid tumors. J Clin Oncol 29: abstract 3010

    Google Scholar 

  61. Alberti L, Carniti C, Miranda C, Roccato E, Pierotti MA (2003) RET and NTRK1 protooncogenes in human diseases. J Cell Physiol 195:168–86

    Article  PubMed  CAS  Google Scholar 

  62. Bongarzone I, Vigneri P, Mariani L, Collini P, Pilotti S, Pierotti MA (1998) RET/NTRK1 rearrangements in thyroid gland tumors of the papillary carcinoma family: correlation with clinicopathological features. Clin Cancer Res 4:223–8

    PubMed  CAS  Google Scholar 

  63. Ju YS, Lee WC, Shin JY, Lee S, Bleazard T, Won JK 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Drilon A, Wang L, Hasanovic A et al (2013) Response to cabozantinib in patients with RET fusion-positive lung adenocarcinomas. Cancer Discov 3:630–5

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Mazieres J, Peters S, Lepage B et al (2013) Lung cancer that harbors a HER2 mutation: epidemiologic characteristics and therapeutic perspectives. J Clin Oncol 31:1997–2003

    Article  PubMed  CAS  Google Scholar 

  66. Arcila ME, Chaft JE, Nafa K et al (2012) Prevalence, clinicopathologic associations, and molecular spectrum of ERBB2 (HER2) tyrosine kinase mutations in lung adenocarcinomas. Clin Cancer Res 18:4910–8

    Article  PubMed  CAS  Google Scholar 

  67. Pelligrini C, Falleni M, Marchetti A et al (2003) HER-2/Neu alterations in non-small cell lung cancer: a comprehensive evaluation by real time reverse transcription-PCR, fluorescence in situ hybridization, and immunohistochemistry. Clin Cancer Res 9:3645–52

    Google Scholar 

  68. Hirsch FR, Varella-Garcia M, Franklin WA et al (2002) Evaluation of HER-2/neu gene amplification and protein expression in non-small cell lung cancer. B J Cancer 86:1449–56

    Article  CAS  Google Scholar 

  69. Davies H, Bignell GR, Cox C et al (2002) Mutations of the BRAF gene in human cancer. Nature 417:949–54

    Article  PubMed  CAS  Google Scholar 

  70. Chapman PB, Hauschild A, Robert C et al (2011) Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 364:2507–16

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Paik PK, Arcila ME, Fara M et al (2011) Clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations. J Clin Oncol 29:2046–51

    Article  PubMed  PubMed Central  Google Scholar 

  72. Marchetti A, Felicioni L, Malatesta S et al (2011) Clinical features and outcome of patients with non–small-cell lung cancer harboring BRAF mutations. J Clin Oncol 29:3574–3579

    Article  PubMed  CAS  Google Scholar 

  73. Kobayashi M, Sonobe M, Takahashi T et al (2011) Clinical significance of BRAF gene mutations in patients with non-small cell lung cancer. Anticancer Res 31:4619–23

    PubMed  CAS  Google Scholar 

  74. Planchard D, Mazieres J, Riely GJ et al (2013) Interim results of phase II study BRF113928 of dabrafenib in BRAF V600E mutation–positive non-small cell lung cancer (NSCLC) patients. J Clin Oncol 31: abstract 8009

    Google Scholar 

  75. Weiss J, Sos ML, Seidel D et al (2010) Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer. Sci Transl Med 2(62):62ra93

    PubMed  PubMed Central  CAS  Google Scholar 

  76. Heist RS, Mino-Kenudson M, Sequist LV et al (2012) FGFR1 amplification in squamous cell carcinoma of the lung. J Thorac Oncol 7:1775–1780

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Cancer Genome Atlas Research Network (2012) Comprehensive genomic characterization of sqaumous cell lung cancer. Nature 489:519–25

    Article  CAS  Google Scholar 

  78. Gadgeel SM, Chen W, Cote ML et al (2013) Fibrobalst growth factor receptor 1 amplification in non-small cell lung cancer by quantitative real time PCR. PLoS One 8:e79820

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Nogova L, Sequist L, Cassier PA et al (2014) Targeting FGFR-1 amplified lung squamous cell carcinoma with selective pan-FGFR inhibitor BGJ398. J Clin Oncol 32: abstract 8034

    Google Scholar 

  80. Paik PK, Shen R, Ferry D et al (2014) A phase Ib open label multicenter study of AZD4547 in patients with advanced squamous cell lung cancers: Preliminary antitumor activity and pharmacodynamic data. J Clin Oncol 32: abstract 8035

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Shirish M. Gadgeel M.D. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Gadgeel, S.M. (2016). Personalized Therapy of Non-small Cell Lung Cancer (NSCLC). In: Ahmad, A., Gadgeel, S. (eds) Lung Cancer and Personalized Medicine: Novel Therapies and Clinical Management. Advances in Experimental Medicine and Biology, vol 890. Springer, Cham. https://doi.org/10.1007/978-3-319-24932-2_11

Download citation

Publish with us

Policies and ethics