Preferences help
enabled [disable] Abstract
Number of results
2018 | 93 | 115-124
Article title

Innovations in lung cancer treatment

Title variants
Languages of publication
Lung cancer is associated with one of the highest mortality rates among malignant tumors. It is the main death cause of men and women in Poland where over 15 000 men and 7 000 women die with this diagnosis annually. 1.7 million people die every year due to lung cancer in the world. Two main types of lung cancer are small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). The history of lung cancer treatment begins with surgical approach followed by addition of chemotherapy and radiotherapy, which were used either separately or in combination depending on the stage of the lung cancer. Many somatic mutations were identified and molecularly targeted therapies could have been established. One of the oldest and the best known group of molecularly targeted drugs used in lung cancer treatment are tyrosine kinase inhibitors (TKIs) of epidermal growth factor receptor (EGFR). First EGFR-TKI was gefitinib, which has been examined in clinical trials before erlotinib, afatinib, dacomitinib and osimertinib. EGFR-TKIs increased overall survival (OS) with significantly less side effects when compared to standard chemotherapy. Another group of molecularly targeted drugs are anaplastic lymphoma (ALK) kinase inhibitors such as crizotinib, alectinib and ceritinib. Another innovation which was introduced in NSCLC treatment was immunotherapy. Its effect is based on modification of immune system leading to activation of cytotoxic T lymphocytes (CTL). Currently nivolumab and pembrolizumab (anti-PD1 antibodies) as well as atezoliumab (anti-PD-L1 antibody) are being used in NSCLC patients. The discovery of innovative therapies for NSCLC patients resulted in significant extension of patients' life expectancy while minimizing the side effects of such therapy. Moreover, the quality of patients’ life was significantly improved. However, important problems still remain to be solved: overcoming the resistance in the course of molecularly targeted therapies and the lack of predictive factors that determine the effectiveness of immunotherapy.
Physical description
  • Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, Poland
  • Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, Poland
  • Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, Poland
  • Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, Poland
  • Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, Poland
  • [1] World Cancer Report 2014. World Health Organization. 2014. pp. Chapter 5.1. ISBN 92-832-0429-8.
  • [2] Didkowska J., Wojciechowska U., Koskinen HL., Tavilla A., Dyba T., Hakulinen T., Future lung cancer incidence in Poland and Finland based on forecasts on hypothetical changes in smoking habits, Acta Oncol. 2011.
  • [3] Didkowska J., Wojciechowska U., Mańczuk M., Łobaszewski J., Lung cancer epidemiology: contemporary and future challenges worldwide, Ann Transl Med. 2016
  • [4] Bilano V., Gilmour S., Moffiet T., Global trends and projections for tobacco use, 1990-2025: an analysis of smoking indicators from the WHO Comprehensive Information Systems for Tobacco Control, Lancet 2015.
  • [5] Ferlay J., Soerjomataram I., Ervik M., Dikshit R., Eser S., Mathers C., Rebelo M., Parkin DM., Forman D., Bray, F., GLOBOCAN 2012 v1.1.
  • [6] Shepherd F. A., Rodrigues Pereira J., Ciuleanu T. iwsp. Erlotinib in previously treated non-small-cell lung cancer. N. Engl. J. Med. 2005; 353: 123–132.
  • [7] Ulivi P., Zoli W., Capelli L., Chiadini E., Calistri D., Amadori D., Target therapy in NSCLC patients: Relevant clinical agents and tumour molecular characterisation (Review), Molecular and Clinical Oncology, 2013.
  • [8] Rosell R., Carcereny E., Gervais R., Vergnenegre A., Massuti B., Felip E., Palmero R., Garcia-Gomez R., Pallares C., Sanchez JM., 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.
  • [9] Cappuzzo F., Coudert B., Wierzbicki R., Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised placebo-controlled phase 3 study, Lancet Oncol. 2010.
  • [10] Győrffy B., Surowiak P., Budczies J., Lánczky A., Online survival analysis software to assess the prognostic value of biomarkers using transcriptomic data in non-small-cell lung cancer, PloS One, 2013.
  • [11] Bethune G., Bethune D., Ridgway N., Xu Z., Epidermal growth factor receptor (EGFR) in lung cancer: an overview and update, J Thorac Dis. 2010.
  • [12] Gao G., Ren S, Li A., Xu J., Xu Q., Su C., Epidermal growth factor receptor-tyrosine kinase inhibitor therapy is effective as first-line treatment of advanced non-small-cell lung cancer with mutated EGFR: a meta-analysis from six phase III randomized controlled trials. Int J Cancer, 2012.
  • [13] Jiang-Yong Y., Si-Fan Y., Shu-Hang W., Hua B., Jun Z., Tong-Tong An., Jian-Chun D., JieW.,Clinical outcomes of EGFR-TKI treatment and genetic heterogeneity in lung adenocarcinoma patients with EGFR mutations on exons 19 and 21, Chin J Cancer. 2016.
  • [14] Krawczyk P., Reszka K., Ramlau R., Powrózek T., Pankowski J., Wojas-Krawczyk K., Kalinka-Warzocha E., Szczęsna A., Nicoś M., Jarosz B., Prevalence of rare EGFR gene mutations in nonsmall-cell lung cancer: A multicenter study on 3856 Polish Caucasian patients, Ann Oncol. 2016.
  • [15] Rosell R., Carcereny E., Gervais R., Vergnenegre A., Massuti B., Felip E., Palmero R., Garcia-Gomez R., Pallares C., Sanchez JM., Porta R., Cobo M., Garrido P., Longo F., Moran T., Insa A., De Marinis F., Corre R., Bover I., Illiano A., Dansin E., de Castro J., Milella M., Reguart N., Altavilla G., Jimenez U., Provencio M., Moreno MA., Terrasa J., Muñoz-Langa J., Valdivia J., Isla D., Domine M., Molinier O., Mazieres J., Baize N., Garcia-Campelo R., Robinet G., Rodriguez-Abreu D., Lopez-Vivanco G., Gebbia V., Ferrera-Delgado L., Bombaron P., Bernabe R., Bearz A., Artal A., Cortesi E., Rolfo C., Sanchez-Ronco M., Drozdowskyj A., Queralt C., de Aguirre I., Ramirez JL., Sanchez JJ., Molina MA., Taron M., Paz-Ares L., 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.
  • [16] Lynch TJ., Bell DW., Sordella R., Gurubhagavatula S., Okimoto RA., Brannigan BW., Harris PL., Haserlat SM., Supko JG., Haluska FG., Louis DN., Christiani DC., Settleman J., Haber DA., Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004.
  • [17] Clark G.M., Prognostic factors versus predictive factors: examples from a clinical trail of erlotinib, Mol Oncol. 2007.
  • [18] Pirker R., Herth FJ., Kerr KM., Filipits M., Taron M., Gandara D., Hirsch FR., Grunenwald D., Popper H., Smit E., Dietel M., Marchetti A., Manegold C., Schirmacher P., Thomas M., Rosell R., Cappuzzo F., Stahel R., Consensus for EGFR mutation testing in non-small cell lung cancer: results from a European workshop, J Thorac Oncol. 2010.
  • [19] Passaro A.,Gori B., Marinis F., Afatinib as first-line treatment for patients with advanced non-small-cell lung cancer harboring EGFR mutations: focus on LUX-Lung 3 and LUX-Lung 6 phase III trials, J Thorac Dis. 2013.
  • [20] Wu YL., Cheng Y., Zhou X., Lee KH., Nakagawa K., Niho S., Tsuji F., Linke R., Rosell R., Corral J., Migliorino MR., Pluzanski A., Sbar EI., Wang T., White JL., Nadanaciva S., Sandin R., Mok TS.,Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial, Lancet Oncol. 2017.
  • [21] Wang S., Cang S., Liu D., Third-generation inhibitors targeting EGFR T790M mutation in advanced non-small cell lung cancer, J HematolOncol., 2016.
  • [22] Harandi A., Zaidi AS., Stocker AM., Laber DA., Clinical efficacy and toxicity of anti-EGFR therapy in common cancers, J Oncol. 2009.
  • [23] Hirsh V., Managing treatment-related adverse events associated with egfr tyrosine kinase inhibitors in advanced non-small-cell lung cancer, Curr Oncol. 2011.
  • [24] Qin A., Gadgeel S., The Current Landscape of Anaplastic Lymphoma Kinase (ALK) in Non-Small Cell Lung Cancer: Emerging Treatment Paradigms and Future Directions, Target Oncol. 2017.
  • [25] GerberD., Minna J., ALK Inhibition for Non-Small Cell Lung Cancer: From Discovery to Therapy in Record Time, Cancer Cell. 2010.
  • [26] Kwak EL., Bang YJ., Camidge DR., Shaw AT., Solomon B., Maki RG., Ou SH., Dezube BJ., Jänne PA., Costa DB., Varella-Garcia M., Kim WH., Lynch TJ., Fidias P., Stubbs H., Engelman JA., Sequist LV., Tan W., Gandhi L., Mino-Kenudson M., Wei GC., Shreeve SM., Ratain MJ., Settleman J., Christensen JG., Haber DA., Wilner K., Salgia R., Shapiro GI., Clark JW., Iafrate AJ., Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer, N Engl J Med. 2010.
  • [27] Lindeman N., Cagle P., Beasley M., Chitale D., Dacic S., Giaccone G., Jenkins R., Kwiatkowski D., Saldivar J., Squire J., Thunnissen E., Ladanyi M., Molecular Testing Guideline for Selection of Lung Cancer Patients for EGFR and ALK Tyrosine Kinase Inhibitors, J Thorac Oncol. 2013.
  • [28] Forde PM., Rudin CM., Crizotinib in the treatment of non-small-cell lung cancer, Expert Opin Pharmacother. 2012.
  • [29] Sahu A., Prabhash K., Noronha V., Joshi A., Desai S., Crizotinib: A comprehensive review, South Asian J Cancer, 2013.
  • [30] Chuang J., Neal J., Crizotinib as first line therapy for advanced ALK-positive non-small cell lung cancers, Transl Lung Cancer Res. 2015.
  • [31] Sullivan I., Planchard D., ALK inhibitors in non-small cell lung cancer: the latest evidence and developments, TherAdv Med Oncol. 2016.
  • [32] Awad MM., Shaw AT., ALK inhibitors in non-small cell lung cancer: crizotinib and beyond, Clin Adv Hematol Oncol. 2014.
  • [33] Noronha V.,Ramaswamy A., Patil V., Joshi A.,Chougule A., Kane S., Kumar S., Sahu A., Doshi V., NayakL., Mahajan A., Janu A., Prabhash K., ALK Positive Lung Cancer: Clinical Profile, Practice and Outcomes in a Developing Country, PLoS One. 2016.
  • [34] Carter BW., Halpenny DF., Ginsberg MS., Papadimitrakopoulou VA., de Groot PM., Immunotherapy in Non-Small Cell Lung Cancer Treatment: Current Status and the Role of Imaging, J Thorac Imaging. 2017.
  • [35] Massarelli E., Papadimitrakopoulou V, Welsh J.,Tang C.,Tsao A., Immunotherapy in lung cancer, Transl Lung Cancer Res. 2014.
  • [36] Carrizosa D., Gold K., New strategies in immunotherapy for non-small cell lung cancer, Transl Lung Cancer Res. 2015.
  • [37] Keating GM., Bevacizumab: a review of its use in advanced cancer, Drugs. 2014.
  • [38] Aspeslagh S., Marabelle A., Soria JC., Armand JP., Upcoming innovations in lung cancer immunotherapy: focus on immune checkpoint inhibitors, Chin Clin Oncol. 2015.
  • [39] Medina P., Adams V., PD‐1 Pathway Inhibitors: Immuno‐Oncology Agents for Restoring Antitumor Immune Responses, Pharmacotherapy, 2016.
  • [40] Taube JM., Klein A., Brahmer JR., Xu H., Pan X., Kim JH., Chen L., Pardoll DM., Topalian SL., Anders RA., Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy, Clin Cancer Res. 2014.
  • [41] Brahmer J., Reckamp KL., Baas P., Crinò L., Eberhardt WE., Poddubskaya E., Antonia S., Pluzanski A., Vokes EE., Holgado E., Waterhouse D., Ready N., Gainor J., ArénFrontera O., Havel L., Steins M., Garassino MC., Aerts JG., Domine M., Paz-Ares L., Reck M., Baudelet C., Harbison CT., Lestini B., Spigel DR., Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer, N Engl J Med. 2015.
  • [42] Borghaei H., Paz-Ares L., Horn L., Spigel DR., Steins M., Ready NE., Chow LQ., Vokes EE., Felip E., Holgado E., Barlesi F., Kohlhäufl M., Arrieta O., Burgio MA., Fayette J., Lena H., Poddubskaya E., Gerber DE., Gettinger SN., Rudin CM., Rizvi N., Crinò L., Blumenschein GR Jr., Antonia SJ., Dorange C., Harbison CT., Graf Finckenstein F., Brahmer JR., Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer, N Engl J Med. 2015.
  • [43] Herbst RS., Baas P., Kim DW., Felip E., Pérez-Gracia JL, Han JY., Molina J., Kim JH., Arvis CD., Ahn MJ., Majem M., Fidler MJ., de Castro G Jr., Garrido M., Lubiniecki GM., Shentu Y., Im E., Dolled-Filhart M., Garon EB., Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial, Lancet 2016.
  • [44] Roach C., Zhang N.,Corigliano E., Jansson M., Toland G., Ponto G., Dolled-Filhart M., Emancipator K., Stanforth D.,Kulangara K., Development of a Companion Diagnostic PD-L1 Immunohistochemistry Assay for Pembrolizumab Therapy in Non–Small-cell Lung Cancer, Appl Immunohistochem Mol Morphol. 2016 Jul; 24(6): 392-7
Document Type
Publication order reference
YADDA identifier
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.