Skip to main content
  • 702 Accesses

Abstract

Systemic therapy for advanced non-small-cell lung cancer (NSCLC) depends upon tumor biology or tumor histology, with targeted agents preferentially used in individuals with a specific driver mutation and chemotherapy used for patients whose tumors do not harbor such mutations, or following failure of targeted therapy.

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 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight 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

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Non-Small Cell Lung Cancer Collaborative Group. Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials. Br Med J. 1995; 311: 899-909.

    Google Scholar 

  2. Non-Small Cell Lung Cancer Collaborative Group. Chemotherapy in addition to supportive care improves survival in advanced non-small-cell lung cancer: a systematic review and metaanalysis of individual patient data from 16 randomized controlled trials. J Clin Oncol. 2008; 26: 4617-4625.

    Google Scholar 

  3. Wozniak AJ, Crowley JJ, Balcerzak SP, et al. 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. 1998;16:2459-2465.

    Google Scholar 

  4. Sandler AB, Nemunaitis J, Denham C, et al. 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. 2000;18:122-130.

    Google Scholar 

  5. Lilenbaum RC, Herndon JE 2nd, List MA, et al. Single-agent versus combination chemotherapy in advanced non-small cell lung cancer: the Cancer and Leukemia Group B (Study 9730). J Clin Oncol. 2005; 23:190-196.

    Google Scholar 

  6. Kelly K, Crowley J, Bunn PA, 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. 2001;19: 3210-3218.

    Google Scholar 

  7. Le Chevalier T, Scagliotti GV, Natale R, et al. Efficacy of gemcitabine plus platinum chemotherapy compared with other platinum containing regimens in advanced non-smallcell lung cancer: a meta-analysis of survival outcomes. Lung Cancer. 2005; 47: 69-80.

    Google Scholar 

  8. Douillard JY, Laporte S, Fossella F, et al. Comparison of docetaxel- and vinca alkaloid-based chemotherapy in the first-line treatment of advanced non-small cell lung cancer: a metaanalysis of seven randomized clinical trials. J Thorac Oncol. 2007; 2: 939-946.

    Google Scholar 

  9. Grossi F, Aita M, Defferrari C, et al. Impact of third-generation drugs on the activity of firstline chemotherapy in advanced non-small cell lung cancer: a meta-analytical approach. Oncologist. 2009;14:497-510.

    Google Scholar 

  10. Ardizzoni A, Boni L, Tiseo M, et al. Cisplatin-versus carboplatin-based chemotherapy in first-line treatment of advanced non-small-cell lung cancer: an individual patient data metaanalysis. J Natl Cancer Inst. 2007; 99: 847-857.

    Google Scholar 

  11. Schiller JH, Harrington D, Belani CP, et al. Comparison of four chemotherapy regimens for advanced non-small cell lung cancer. N Engl J Med. 2002; 346: 92-98.

    Google Scholar 

  12. Scagliotti GV, De Marinis F, Rinaldi M, et al. Phase III randomized trial comparing three platinumbased doublets in advanced non–small-cell lung cancer. J Clin Oncol. 2002; 20: 4285-4291.

    Google Scholar 

  13. Fossella F, Pereira JR, von Pawel J, et al. 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. 2003; 21:3016-3024.

    Google Scholar 

  14. Delbaldo C, Michiels S, Syz N, et al. 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. 2004; 292:470-484.

    Google Scholar 

  15. 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 nonsmall-cell lung cancer. J Clin Oncol. 2008;26:3543-3551.

    Google Scholar 

  16. Ceppi P, Volante M, Saviozzi S, et al. Squamous cell carcinoma of the lung compared with other histotypes shows higher messenger RNA and protein levels for thymidylate synthase. Cancer. 2006;107:1589-1596.

    Google Scholar 

  17. Johnson DH, Fehrenbacher L, Novotny WF, et al. 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. 2004; 22: 2184–2191.

    Google Scholar 

  18. Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for nonsmall-cell lung cancer. N Engl J Med. 2006; 355: 2542-2550.

    Google Scholar 

  19. Sandler A, Yi J, Dahlberg S, Kolb MM, et al. Treatment outcomes by tumor histology in Eastern Cooperative Group study E4599 of bevacizumab with paclitaxel/carboplatin for advanced non-small cell lung cancer. J Thorac Oncol. 2010;5:1416-1423.

    Google Scholar 

  20. Reck M, von Pawel J, Zatloukal P, et al. Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil. J Clin Oncol. 2009; 27:1227-1234.

    Google Scholar 

  21. Soria JC, Mauguen A, Reck M, et al. Systematic review and meta-analysis of randomised, phase II/III trials adding bevacizumab to platinum-based chemotherapy as first-line treatment in patients with advanced non-small-cell lung cancer. Ann Oncol. 2013; 24:20-30.

    Google Scholar 

  22. Socinski MA, Langer CJ, Huang JE, et al. Safety of bevacizumab in patients with non-small-cell lung cancer and brain metastases. J Clin Oncol. 2009; 27:5255-5261.

    Google Scholar 

  23. Wozniak AJ, Garst J, Jahanzeb M, et al. Clinical outcomes (CO) for special populations of patients (pts) with advanced non-small cell lung cancer (NSCLC): results from ARIES, a bevacizumab (BV) observational cohort study (OCS). J Clin Oncol. 2010; 28 (abstr 7618).

    Google Scholar 

  24. Crinò L, Dansin E, Garrido P, et al. Safety and efficacy of first-line bevacizumab-based therapy in advanced non-squamous non-small-cell lung cancer (SAiL, MO19390): a phase 4 study. Lancet Oncol. 2010;11:733-740.

    Google Scholar 

  25. Johnson BE, Kabbinavar F, Fehrenbacher L, et al. ATLAS: randomized, double-blind, placebocontrolled, phase IIIB trial comparing bevacizumab therapy with or without erlotinib, after completion of chemotherapy, with bevacizumab for first-line treatment of advanced nonsmall-cell lung cancer. J Clin Oncol. 2013; 31:3926-3934.

    Google Scholar 

  26. Patel J, Socinski MA, Garon EB, et al. 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. 2013; 31:4349-4357.

    Google Scholar 

  27. Zinner R, Ross HJ, Weaver R, et al. Randomized, open-label, phase III study of pemetrexed plus carboplatin (PemC) followed by maintenance pemetrexed versus paclitaxel/carboplatin/bevacizumab (PCB) followed by maintenance bevacizumab in patients with advanced nonsquamous (NS) non-small cell lung cancer (NSCLC). J Clin Oncol. 2013; 31 (suppl; abstr LBA8003).

    Google Scholar 

  28. Ranson M, Hammond LA, Ferry D, et al. ZD1839, a selective oral epidermalgrowth factor receptor-tyrosine kinaseinhibitor, is well tolerated and active inpatients with solid, malignant tumors: results of a Phase I trial. J Clin Oncol. 2002;20:2240-2250.

    Google Scholar 

  29. Ciardiello F, Caputo R, Bianco R, et al. Antitumor effect and potentiation ofcytotoxic drugs activity in human cancercells by ZD-1839 (Iressa), an epidermalgrowth factor receptorselective tyrosine kinase inhibitor. Clin Cancer Res. 2000;6:2053-2063.

    Google Scholar 

  30. Swaisland H, Laight A, Stafford L, et al. Pharmacokinetics and tolerability of the orally active selective epidermal growth factor receptor tyrosine kinase inhibitorZD1839 in healthy volunteers. Clin Pharmacokinet. 2001;40:297-306.

    Google Scholar 

  31. Swaisland HC, Cantarini MV, Fuhr R, et al. Exploring the relationship betweenexpression of cytocrome P450 enzymesand gefitinib pharmacokinetics. Clin Pharmacokinet 2006;45:633-644.

    Google Scholar 

  32. Swaisland HC, Ranson M, Smith RP, et al. Pharmacokinetic drug interactionsof gefitinib with rifampicin, itraconazoleand metoprolol. Clin Pharmacokinet. 2005;44:1076-1081.

    Google Scholar 

  33. Heimberger AB, Learn CA, Archer GE, et al. Brain tumors in mice are susceptible to blockade of EpidermalGrowth Factor Receptor (EGFR) withthe oral, specific, EGFR-tyrosine kinase inhibitor ZD1839 (Iressa). Clin Cancer Res. 2002; 8:3496-3502.

    Google Scholar 

  34. Cappuzzo F, Ardizzoni A, Soto-Parra H, et al. Epidermal growth factor receptor targeted therapy by ZD 1839 (Iressa) in patients with brain metastases from non-small cell lung cancer (NSCLC). Lung Cancer. 2003;41: 227-231.

    Google Scholar 

  35. Ceresoli GL, Cappuzzo F, Gregorc V, et al. Gefitinib in patients with brain metastases from nonsmall-cell lung cancer: a prospective trial. Ann Oncol. 2004;15:1042-1047.

    Google Scholar 

  36. Hotta K, Kiura K, Ueoka H, et al. Effectof gefitinib (‘Iressa’, ZD1839) on brain metastases in patients with advancednon-small-cell lung cancer. Lung Cancer. 2004;46:255-261.

    Google Scholar 

  37. Namba Y, Kijima T, Yokota S, et al. Gefitinib in patients with brain metastases from non-smallcell lung cancer: review of 15 clinical cases. Clin Lung Cancer. 2004; 6:123-128.

    Google Scholar 

  38. Johnson JR, Cohen M, Sridhara R, et al. Approval summary for erlotinib for treatment of patients with locally advanced or metastatic of non-small cell lung cancer after failure of at least one prior chemotherapy regimen. Clin Cancer Res. 2005; 11:6414-6421.

    Google Scholar 

  39. Meany HJ, Fox E, McCully C, et al. The plasma and cerebrospinal fluid pharmacokinetics of erlotinib and its active metabolite (OSI-420) after intravenous administration of erlotinib in non-human primates. Cancer Chemother Pharmacol. 2008; 62:387-392.

    Google Scholar 

  40. Speake G. A pharmacological comparison of gefitinib (IRESSA) and erlotinib. 97th American Association of Cancer Research Annual Meeting, Washington, DC, USA 2006; poster 3784.

    Google Scholar 

  41. Yuza Y, Glatt KA, Jiang J, et al. Allele-dependent variation in the relative cellular potency of distinct EGFR inhibitors. Cancer Biol Ther. 2007; 6:661-667.

    Google Scholar 

  42. Li D, Ambrogio L, Shimamura T, et al: BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene. 2008; 27:4702-4711.

    Google Scholar 

  43. Wind S, Schmid M, Erhardt J, et al. Pharmacokinetics of afatinib, a selective irreversible ErbB family blocker, in patients with advanced solid tumours. Clin Pharmacokinet. 2013;52:1101-1109.

    Google Scholar 

  44. Yap TA, Vidal L, Adam J, et al. Phase I trial of the irreversible ErbB1 (EGFR) and ErbB2 (HER2) kinase inhibitor BIBW 2992 in patients with advanced solid tumours. J Clin Oncol 2010; 28: 3965-3972.

    Google Scholar 

  45. Mok TS, Wu Yl, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009; 361:947-957.

    Google Scholar 

  46. Han JY, Park K, Kim SW, et al. First-SIGNAL: first-line single-agent iressa versus gemcitabine and cisplatin trial in never-smokers with adenocarcinoma of the lung. J Clin Oncol. 2012; 30:1122-1128.

    Google Scholar 

  47. Mitsudomi T, Morita S, Yatabe Y, et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): An open label, randomised phase 3 trial. Lancet Oncol. 2010; 11:121-128.

    Google Scholar 

  48. 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.

    Google Scholar 

  49. Zhou C, Wu YL, Chen G, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-smallcell lung cancer (OPTIMAL, CTONG-0802): A multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2011; 12:735-742.

    Google Scholar 

  50. 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.

    Google Scholar 

  51. Wu YL, Liam CK, Zhou C, et al. First-line erlotinib versus cisplatin/gemcitabine (GP) in patients with advanced EGFR mutation-positive non-small-cell lung cancer (NSCLC): interim analyses from the phase 3, open-label, ENSURE study. J Thorac Oncol. 2013; 8:s603 (Suppl. 2).

    Google Scholar 

  52. Sequist LV, Yang JC, Yamamoto N, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013;31: 3327-3334.

    Google Scholar 

  53. Wu YL, Zhou C, Hu CP, et al. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harboring EGFR mutations (LUXLung 6): an opel-label, randomised phase 3 trial. Lancet Oncol. 2014;15:213-222.

    Google Scholar 

  54. Yang JC, Wu J C-H, Schuler YL, 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. 2015;16:141-151.

    Google Scholar 

  55. Katakami N, Morita S, Yoshioka H, et al. Randomized phase III study comparing gefitinib (G) with erlotinib (E) in patients (pts) with previously treated advanced lung adenocarcinoma (LA): WJOG 5108L. J Clin Oncol. 2014; 32:5s, (suppl; abstr 8041).

    Google Scholar 

  56. Ramalingam SS, Jänne PA, Mok T, et al. Dacomitinib versus erlotinib in patients with advanced stage, previously treated non-small-cell lung cancer (ARCHER 1009): a randomised, doubleblind, phase 3 trial. Lancet Oncol. 2014;15:1369-1378.

    Google Scholar 

  57. 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. 2008; 14: 4275-4283.

    Google Scholar 

  58. Wong DW, Leung EL, So KK, et al. The EML4-ALK fusion gene is involved in various histologic types of lung cancers from non smokers with wild-type EGFR and KRAS. Cancer. 2009; 115:1723-1733.

    Google Scholar 

  59. Shaw AT, Yeap BY, Mino-Kenudson M, et al. Clinical features and outcome of patients with nonsmall-cell lung cancer who harbour EML4-ALK. J Clin Oncol. 2009; 27: 4247-4253.

    Google Scholar 

  60. Inamura K, Takeuchi K, Togashi Y, et al. EML4-ALK lung cancers are characterized by rare other mutations, a TTF-1 cell lineage, an acinar histology, and young onset. Mod Pathol. 2009;22:508-515.

    Google Scholar 

  61. Bang YJ, Treatment of ALK-positive non-small cell lung cancer. Arch Pathol Lab Med. 2012;136:1201-1204

    Google Scholar 

  62. Thunnissen E, Bubendorf L, Manfred D, et al. EML4-ALK testing in non-small cell carcinomas of the lung: a review with recommendations. Virchows Arch. 2012; 461:245-257.

    Google Scholar 

  63. Horn L, and Pao W, EML4-ALK: homing in on a new target in non-small-cell lung cancer. J Clin Oncol. 2009; 27: 4232-4235.

    Google Scholar 

  64. Cui JJ, Tran-Dubé M, Shen H, et al. Structure based drug design of crizotinib (PF-02341066), a potent and selective dual inhibitor of mesenchymal-epithelial transition factor (c-MET) kinase and anaplastic lymphoma kinase (ALK). J Med Chem. 2011; 54:6342-6363.

    Google Scholar 

  65. Tanizaki J, Okamoto I, Okamoto K, et al. MET tyrosine kinase inhibitor crizotinib (PF-02341066) shows differential antitumor effects in non-small cell lung cancer according to MET alterations. J Thorac Oncol. 2011; 6:1624-1631.

    Google Scholar 

  66. 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.

    Google Scholar 

  67. Camidge DR, Bang YJ, Kwak EL, et al. Activity and safety of crizotinib in patients with ALKpositive non-small-cell lung cancer: updated results from a phase 1 study. Lancet Oncol. 2012;13:1011-1019.

    Google Scholar 

  68. Shaw AT, Kim DW, Nakagawa K, et al. Crizotinib versus chemotherapy in advanced ALKpositive lung cancer. N Engl J Med, 2013; 368: 2385–94.

    Google Scholar 

  69. Mok T, Kim D-W, Wu Y-L, et al. First-line crizotinib versus pemetrexed–cisplatin or pemetrexed–carboplatin in patients (pts) with advanced ALK-positive non-squamous non-small cell lung cancer (NSCLC): results of a phase III study (PROFILE 1014). J Clin Oncol. 2014; 32:5s (suppl; abstr 8002).

    Google Scholar 

  70. Kwak EL, Camidge DR, Clark J, et al. Clinical activity observed in a phase I dose escalation trial of an oral anti c-met and ALK inhibitor, PF-02341066. J Clin Oncol. 2009; 27; 15 (suppl; abstract 3509).

    Google Scholar 

  71. Ou SH, Kwak EL, Siwak-Tapp C, et al. Activity of crizotinib (PF02341066), a dual mesenchymalepithelial transition (MET) and anaplastic lymphoma kinase (ALK) inhibitor, in a non-small cell lung cancer patient with de novo MET amplification. J Thorac Oncol. 2011; 6:942-946.

    Google Scholar 

  72. Lennerz JK, Kwak EL, Ackerman A, et al. MET Amplification Identifies a Small and Aggressive Subgroup of Esophagogastric Adenocarcinoma With Evidence of Responsiveness to Crizotinib. J Clin Oncol. 2011;29:4803-4810.

    Google Scholar 

  73. Chi AS, Batchelor TT, Kwak EL, et al. Radiographic and Clinical Improvement After Treatment of a MET-Amplified Recurrent Glioblastoma With a Mesenchymal-Epithelial Transition Inhibitor. J Clin Oncol. 2012;30:e30-e33.

    Google Scholar 

  74. Kim D-W, Ahn MJ, Shi Y, et al. Results of a global phase II study with crizotinib in advanced ALK positive non-small cell lung cancer. J Clin Oncol. 2012; 30: abstract 7533.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Cappuzzo, F. (2015). Therapy options for advanced NSCLC. In: Guide to Targeted Therapies: Treatment Resistance in Lung Cancer. Adis, Cham. https://doi.org/10.1007/978-3-319-20741-4_2

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-20741-4_2

  • Published:

  • Publisher Name: Adis, Cham

  • Print ISBN: 978-3-319-20740-7

  • Online ISBN: 978-3-319-20741-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics