Download PDF
Semin intervent Radiol 2013; 30(02): 191-198
DOI: 10.1055/s-0033-1342961
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Non–Small-Cell Lung Cancer: Treatment of Late Stage Disease: Chemotherapeutics and New Frontiers

Ronald J. Scheff
1   Division of Hematology/Oncology, Department of Internal Medicine, Weill Cornell Medical College, New York, New York
,
Bryan J. Schneider
1   Division of Hematology/Oncology, Department of Internal Medicine, Weill Cornell Medical College, New York, New York
› Author Affiliations
Further Information

Publication History

Publication Date:
28 May 2013 (online)

Also available at
    Permissions and Reprints

Corrected by:

Non–Small-Cell Lung Cancer: Treatment of Late Stage Disease: Chemotherapeutics and New Frontiers Semin intervent Radiol 2013; 30(02): e1-e1
DOI: 10.1055/s-0033-1349396

Abstract

Systemic therapy should be considered in patients with advanced non–small cell lung cancer (NSCLC) who are no longer amenable to local therapies. Systemic therapy has been shown to improve survival and preserve quality of life in patients with a reasonable performance status. In unselected patients, the standard of care for initial therapy remains platinum-based chemotherapy. At progression, further treatment typically consists of the sequential administration of single-agent therapy, which has also been shown to improve survival and reduce cancer-related symptoms. Molecular biomarkers are essential to guide targeted agents. This analysis requires ample tumor DNA; thus adequate biopsy samples are critical to guide therapeutic options. More biomarkers are currently being validated and may potentially have specific targeted therapy. In the near future, it is likely that rapid multiplexed genotype testing will help reduce the need for large amounts of tumor for analysis and will promote personalized cancer therapy. We review recent changes in the definition of stage IV NSCLC and review current and future systemic therapeutic approaches for patients with advanced disease.

Keywords

non–small cell lung cancer - chemotherapy - systemic therapy - targeted therapy
 

  • References

  • 1 American Cancer Society. Cancer facts and figures 2012. Atlanta, GA: 2012. Available at: http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-031941.pdf
    PubMedGoogle Scholar
  • 2 Rapp E, Pater JL, Willan A , et al. Chemotherapy can prolong survival in patients with advanced non-small-cell lung cancer—report of a Canadian multicenter randomized trial. J Clin Oncol 1988; 6 (4) 633-641
    PubMedGoogle Scholar
  • 3 Marino P, Pampallona S, Preatoni A, Cantoni A, Invernizzi F. Chemotherapy vs supportive care in advanced non-small-cell lung cancer. Results of a meta-analysis of the literature. Chest 1994; 106 (3) 861-865
    CrossrefPubMedGoogle Scholar
  • 4 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. BMJ 1995; 311 (7010) 899-909
    CrossrefPubMedGoogle Scholar
  • 5 Rami-Porta R, Crowley JJ, Goldstraw P. The revised TNM staging system for lung cancer. Ann Thorac Cardiovasc Surg 2009; 15 (1) 4-9
    PubMedGoogle Scholar
  • 6 Postmus PE, Brambilla E, Chansky K , et al; International Association for the Study of Lung Cancer International Staging Committee; Cancer Research and Biostatistics; Observers to the Committee; Participating Institutions. The IASLC Lung Cancer Staging Project: proposals for revision of the M descriptors in the forthcoming (seventh) edition of the TNM classification of lung cancer. J Thorac Oncol 2007; 2 (8) 686-693
    CrossrefPubMedGoogle Scholar
  • 7 Tanvetyanon T, Robinson LA, Schell MJ , et al. Outcomes of adrenalectomy for isolated synchronous versus metachronous adrenal metastases in non-small-cell lung cancer: a systematic review and pooled analysis. J Clin Oncol 2008; 26 (7) 1142-1147
    CrossrefPubMedGoogle Scholar
  • 8 Ardizzoni A, Boni L, Tiseo M , et al; CISCA (CISplatin versus CArboplatin) Meta-analysis Group. Cisplatin- versus carboplatin-based chemotherapy in first-line treatment of advanced non-small-cell lung cancer: an individual patient data meta-analysis. J Natl Cancer Inst 2007; 99 (11) 847-857
    CrossrefPubMedGoogle Scholar
  • 9 Schiller JH, Harrington D, Belani CP , et al; Eastern Cooperative Oncology Group. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 2002; 346 (2) 92-98
    CrossrefPubMedGoogle Scholar
  • 10 Herbst RS, Khuri FR, Lu C , et al. The novel and effective nonplatinum, nontaxane combination of gemcitabine and vinorelbine in advanced nonsmall cell lung carcinoma: potential for decreased toxicity and combination with biological therapy. Cancer 2002; 95 (2) 340-353
    CrossrefPubMedGoogle Scholar
  • 11 Jiang J, Liang X, Zhou X, Huang R, Chu Z, Zhan Q. Non-platinum doublets were as effective as platinum-based doublets for chemotherapy-naïve advanced non-small-cell lung cancer in the era of third-generation agents. J Cancer Res Clin Oncol 2013; 139 (1) 25-38
    CrossrefPubMedGoogle Scholar
  • 12 Molina JR, Adjei AA. The role of Pemetrexed (Alimta, LY231514) in lung cancer therapy. Clin Lung Cancer 2003; 5 (1) 21-27
    CrossrefPubMedGoogle Scholar
  • 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 (21) 3543-3551
    CrossrefPubMedGoogle Scholar
  • 14 Socinski MA, Schell MJ, Peterman A , et al. Phase III trial comparing a defined duration of therapy versus continuous therapy followed by second-line therapy in advanced-stage IIIB/IV non-small-cell lung cancer. J Clin Oncol 2002; 20 (5) 1335-1343
    CrossrefPubMedGoogle Scholar
  • 15 Soon YY, Stockler MR, Askie LM, Boyer MJ. Duration of chemotherapy for advanced non-small-cell lung cancer: a systematic review and meta-analysis of randomized trials. J Clin Oncol 2009; 27 (20) 3277-3283
    CrossrefPubMedGoogle Scholar
  • 16 Sandler A, Gray R, Perry MC , et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 2006; 355 (24) 2542-2550
    CrossrefPubMedGoogle Scholar
  • 17 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 (31) 5255-5261
    CrossrefPubMedGoogle Scholar
  • 18 Pirker R, Pereira JR, Szczesna A , et al; FLEX Study Team. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet 2009; 373 (9674) 1525-1531
    CrossrefPubMedGoogle Scholar
  • 19 Lynch TJ, Patel T, Dreisbach L , et al. Cetuximab and first-line taxane/carboplatin chemotherapy in advanced non-small-cell lung cancer: results of the randomized multicenter phase III trial BMS099. J Clin Oncol 2010; 28 (6) 911-917
    CrossrefPubMedGoogle Scholar
  • 20 Paz-Ares L, De Marinis F, Dediu M , et al. PARAMOUNT: Final overall survival (OS) results of the phase III study of maintenance pemetrexed (pem) plus best supportive care (BSC) versus placebo (plb) plus BSC immediately following induction treatment with pem plus cisplatin (cis) for advanced nonsquamous (NS) non-small cell lung cancer (NSCLS). J Clin Oncol 2012; 30 (suppl): Abstract LBA7507
    PubMedGoogle Scholar
  • 21 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 2009; 374 (9699) 1432-1440
    CrossrefPubMedGoogle Scholar
  • 22 Fidias PM, Dakhil SR, Lyss AP , et al. 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 2009; 27 (4) 591-598
    CrossrefPubMedGoogle Scholar
  • 23 Sridhar SS, Seymour L, Shepherd FA. Inhibitors of epidermal-growth-factor receptors: a review of clinical research with a focus on non-small-cell lung cancer. Lancet Oncol 2003; 4 (7) 397-406
    CrossrefPubMedGoogle Scholar
  • 24 Cappuzzo F, Ciuleanu T, Stelmakh L , et al; SATURN investigators. Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol 2010; 11 (6) 521-529
    CrossrefPubMedGoogle Scholar
  • 25 Shepherd FA, Dancey J, Ramlau R , et al. Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J Clin Oncol 2000; 18 (10) 2095-2103
    CrossrefPubMedGoogle Scholar
  • 26 Hanna N, Shepherd FA, Fossella FV , et al. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol 2004; 22 (9) 1589-1597
    CrossrefPubMedGoogle Scholar
  • 27 Shepherd FA, Rodrigues Pereira J, Ciuleanu T , et al; National Cancer Institute of Canada Clinical Trials Group. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 2005; 353 (2) 123-132
    CrossrefPubMedGoogle Scholar
  • 28 Noble J, Ellis PM, Mackay JA, Evans WK. Lung Cancer Disease Site Group of Cancer Care Ontario's Program in Evidence-based Care. Second-line or subsequent systemic therapy for recurrent or progressive non-small cell lung cancer: a systematic review and practice guideline. J Thorac Oncol 2006; 1 (9) 1042-1058
    CrossrefPubMedGoogle Scholar
  • 29 Crinò L, Mosconi AM, Scagliotti G , et al. Gemcitabine as second-line treatment for advanced non-small-cell lung cancer: a phase II trial. J Clin Oncol 1999; 17 (7) 2081-2085
    PubMedGoogle Scholar
  • 30 Lara Jr PN, Gumerlock PH, Mack PC , et al. Gemcitabine in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy: a phase II California cancer consortium trial. Clin Lung Cancer 2004; 6 (2) 102-107
    CrossrefPubMedGoogle Scholar
  • 31 Santoro A, Maiorino L, Santoro M. Second-line with vinorelbine in the weekly monochemotherapy for the treatment of advanced non-small cell lung cancer. Lung Cancer 1994; 11: S130
    PubMedGoogle Scholar
  • 32 Di Maio M, Chiodini P, Georgoulias V , et al. Meta-analysis of single-agent chemotherapy compared with combination chemotherapy as second-line treatment of advanced non-small-cell lung cancer. J Clin Oncol 2009; 27 (11) 1836-1843
    CrossrefPubMedGoogle Scholar
  • 33 Fossella FV, DeVore R, Kerr RN , et al. Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens. The TAX 320 Non-Small Cell Lung Cancer Study Group. J Clin Oncol 2000; 18 (12) 2354-2362
    CrossrefPubMedGoogle Scholar
  • 34 Miller VA, Fossella FV, DeVore R , et al. Docetaxel benefits lung cancer symptoms and quality of life in a randomized phase III study of non-small cell lung cancer patients previously treated with platinum-based therapy. Proc Am Soc Clin Oncol 1999; 18: 491a
    PubMedGoogle Scholar
  • 35 Dancey J, Shepherd F, Ramlau R , et al. Quality of life assessment in a randomized study of taxotere versus best supportive care in non-small cell lung cancer patients previously treated with platinum-based chemotherapy. Proc Am Soc Clin Oncol 1999; 18: 491a
    PubMedGoogle Scholar
  • 36 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 2004; 22 (5) 777-784
    CrossrefPubMedGoogle Scholar
  • 37 Herbst RS, Giaccone G, Schiller JH , et al. Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial—INTACT 2. J Clin Oncol 2004; 22 (5) 785-794
    CrossrefPubMedGoogle Scholar
  • 38 Gatzemeier U, Pluzanska A, Szczesna A , et al. Phase III study of erlotinib in combination with cisplatin and gemcitabine in advanced non-small-cell lung cancer: the Tarceva Lung Cancer Investigation Trial. J Clin Oncol 2007; 25 (12) 1545-1552
    CrossrefPubMedGoogle Scholar
  • 39 Herbst RS, Prager D, Hermann R , et al; TRIBUTE Investigator Group. TRIBUTE: a phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol 2005; 23 (25) 5892-5899
    CrossrefPubMedGoogle Scholar
  • 40 Mok TS, Wu YL, Thongprasert S , et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361 (10) 947-957
    CrossrefPubMedGoogle Scholar
  • 41 Rosell R, Carcereny E, Gervais R , et al; Spanish Lung Cancer Group in collaboration with Groupe Français de Pneumo-Cancérologie and Associazione Italiana Oncologia Toracica. 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 (3) 239-246
    CrossrefPubMedGoogle Scholar
  • 42 Zhou C, Wu YL, Chen G , et al. 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 2011; 12 (8) 735-742
    CrossrefPubMedGoogle Scholar
  • 43 Maemondo M, Inoue A, Kobayashi K , et al; North-East Japan Study Group. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 2010; 362 (25) 2380-2388
    CrossrefPubMedGoogle Scholar
  • 44 Mitsudomi T, Morita S, Yatabe Y , et al; West Japan Oncology Group. 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 (2) 121-128
    CrossrefPubMedGoogle Scholar
  • 45 Yang JC, Schuler MH, Yamamoto N , et al. LUX-Lung3: a randomized, open label, phase III study of afatinib versus pemetrexed and cisplatin as first-line treatment for patients with advanced adenocarcinoma of the lung harboring EGFR-activating mutations. J Clin Oncol 2012; 30 (suppl): Abstract LBA7500
    PubMedGoogle Scholar
  • 46 Kim DW, Ahn MJ, Shi Y , et al. Results of a global phase II study with crizotinib in advanced ALK-positive non-small cell lung cancer (NSCLC). J Clin Oncol 2012; 30 (suppl): Abstract 7533
    PubMedGoogle Scholar
  • 47 Camidge DR, Bang YJ, Kwak EL , et al. Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study. Lancet Oncol 2012; 13 (10) 1011-1019
    CrossrefPubMedGoogle Scholar
  • 48 Tsao MS, Aviel-Ronen S, Ding K , et al. Prognostic and predictive importance of p53 and RAS for adjuvant chemotherapy in non small-cell lung cancer. J Clin Oncol 2007; 25 (33) 5240-5247
    CrossrefPubMedGoogle Scholar
  • 49 Pao W, Wang TY, Riely GJ , et al. KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med 2005; 2 (1) e17
    CrossrefPubMedGoogle Scholar
  • 50 Janne PA, Shaw AT, Pereira JR , et al. Phase II double-blind, randomized study of selumetinib (SEL) plus docetaxel (DOC) versus DOC plus placebo as second-line treatment for advanced KRAS mutant non-small cell lung cancer (NSCLC). J Clin Oncol 2012; 30 (suppl): Abstract 7503
    PubMedGoogle Scholar
  • 51 Bergethon K, Shaw AT, Ou SH , et al. ROS1 rearrangements define a unique molecular class of lung cancers. J Clin Oncol 2012; 30 (8) 863-870
    CrossrefPubMedGoogle Scholar
  • 52 Shaw AT, Camidge DR, Engelman JA , et al. Clinical activity of crizotinib in advanced non-small cell lung cancer (NSCLC) harboring ROS1 gene rearrangement. J Clin Oncol 2012; 30 (suppl): Abstract 7508
    PubMedGoogle Scholar
  • 53 Suehara Y, Arcila ME, Dela Cruz Drillon AE , et al. KIF5B-RET: Discovery of a novel fusion oncogene in lung adenocarcinomas by a systematic screen for tyrosine kinase fusions and identification of patients for a RET targeted therapy trial. J Clin Oncol 2012; 30 (suppl): Abstract 7578
    PubMedGoogle Scholar
  • 54 Paik PK, Arcila ME, Fara M , et al. Clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations. J Clin Oncol 2011; 29 (15) 2046-2051
    CrossrefPubMedGoogle Scholar
  • 55 Marchetti A, Felicioni L, Malatesta S , et al. Clinical features and outcome of patients with non-small-cell lung cancer harboring BRAF mutations. J Clin Oncol 2011; 29 (26) 3574-3579
    CrossrefPubMedGoogle Scholar
  • 56 Brahmer JR, Horn L, Antonia S , et al. Clinical activity and safety of anti-PD1 (BMS-936558, MDX-1106) in patients with advanced non-small-cell lung cancer (NSCLC). J Clin Oncol 2012; 30 (suppl): Abstract 7509
    PubMedGoogle Scholar
  • 57 National Comprehensive Cancer Network®, NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®); Non-Small Cell Lung Cancer: Version 2. 2012. Available at: http://www.tri-kobe.org/nccn/guideline/lung/english/non_small.pdf
    PubMedGoogle Scholar
  • 58 Meyerson M, Gabriel S, Getz G. Advances in understanding cancer genomes through second-generation sequencing. Nat Rev Genet 2010; 11 (10) 685-696
    CrossrefPubMedGoogle Scholar
  • 59 Paik PK, Hasanovic A, Wang L , et al. Multiplex testing for driver mutations in squamous cell carcinomas of the lung. J Clin Oncol 2012; 30 (suppl): Abstract 7505
    PubMedGoogle Scholar
  • 60 Sequist LV, Heist RS, Shaw AT , et al. Implementing multiplexed genotyping of non-small-cell lung cancers into routine clinical practice. Ann Oncol 2011; 22 (12) 2616-2624
    CrossrefPubMedGoogle Scholar