Targeted Therapy for Non-small Cell Lung Cancer: Current Standards and the Promise of the Future

Overview

Journal Transl Lung Cancer Res

Date 2015 Mar 26

PMID 25806345

Citations 366

Authors

Bryan A Chan

Brett G M Hughes

Affiliations

Soon will be listed here.

Abstract

In recent years, there has been a major paradigm shift in the management of non-small cell lung cancer (NSCLC). NSCLC should now be further sub-classified by histology and driver mutation if one is known or present. Translational research advances now allow such mutations to be inhibited by either receptor monoclonal antibodies (mAb) or small molecule tyrosine kinase inhibitors (TKI). Whilst empirical chemotherapy with a platinum-doublet remains the gold standard for advanced NSCLC without a known driver mutation, targeted therapy is pushing the boundary to significantly improve patient outcomes and quality of life. In this review, we will examine the major subtypes of oncogenic drivers behind NSCLC as well as the development of targeted agents available to treat them both now and in the foreseeable future.

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References

Jackman D, Yeap B, Sequist L, Lindeman N, Holmes A, Joshi V . Exon 19 deletion mutations of epidermal growth factor receptor are associated with prolonged survival in non-small cell lung cancer patients treated with gefitinib or erlotinib. Clin Cancer Res. 2006; 12(13):3908-14. DOI: 10.1158/1078-0432.CCR-06-0462. View

Ou S, Tan J, Yen Y, Soo R . ROS1 as a 'druggable' receptor tyrosine kinase: lessons learned from inhibiting the ALK pathway. Expert Rev Anticancer Ther. 2012; 12(4):447-56. DOI: 10.1586/era.12.17. View

Rosell R, Moran T, Queralt C, Porta R, Cardenal F, Camps C . Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med. 2009; 361(10):958-67. DOI: 10.1056/NEJMoa0904554. View

Hammerman P, Sos M, Ramos A, Xu C, Dutt A, Zhou W . Mutations in the DDR2 kinase gene identify a novel therapeutic target in squamous cell lung cancer. Cancer Discov. 2012; 1(1):78-89. PMC: 3274752. DOI: 10.1158/2159-8274.CD-11-0005. View

Giaccone G . Epidermal growth factor receptor inhibitors in the treatment of non-small-cell lung cancer. J Clin Oncol. 2005; 23(14):3235-42. DOI: 10.1200/JCO.2005.08.409. View

Spigel D, Edelman M, Mok T, OByrne K, Paz-Ares L, Yu W . Treatment Rationale Study Design for the MetLung Trial: A Randomized, Double-Blind Phase III Study of Onartuzumab (MetMAb) in Combination With Erlotinib Versus Erlotinib Alone in Patients Who Have Received Standard Chemotherapy for Stage IIIB or IV.... Clin Lung Cancer. 2012; 13(6):500-4. DOI: 10.1016/j.cllc.2012.05.009. View

Camidge D, Bang Y, Kwak E, Iafrate A, Varella-Garcia M, Fox S . 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):1011-9. PMC: 3936578. DOI: 10.1016/S1470-2045(12)70344-3. View

Bergethon K, Shaw A, Ou S, Katayama R, Lovly C, McDonald N . ROS1 rearrangements define a unique molecular class of lung cancers. J Clin Oncol. 2012; 30(8):863-70. PMC: 3295572. DOI: 10.1200/JCO.2011.35.6345. View

Sattler M, Reddy M, Hasina R, Gangadhar T, Salgia R . The role of the c-Met pathway in lung cancer and the potential for targeted therapy. Ther Adv Med Oncol. 2011; 3(4):171-84. PMC: 3150066. DOI: 10.1177/1758834011408636. View

10.

Giaccone G, Herbst R, Manegold C, Scagliotti G, Rosell R, Miller V . 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):777-84. DOI: 10.1200/JCO.2004.08.001. View

11.

Maruyama R, Nishiwaki Y, Tamura T, Yamamoto N, Tsuboi M, Nakagawa K . Phase III study, V-15-32, of gefitinib versus docetaxel in previously treated Japanese patients with non-small-cell lung cancer. J Clin Oncol. 2008; 26(26):4244-52. DOI: 10.1200/JCO.2007.15.0185. View

12.

Alamgeer M, Ganju V, Watkins D . Novel therapeutic targets in non-small cell lung cancer. Curr Opin Pharmacol. 2013; 13(3):394-401. DOI: 10.1016/j.coph.2013.03.010. View

13.

Herbst R, Prager D, Hermann R, Fehrenbacher L, Johnson B, Sandler A . 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):5892-9. DOI: 10.1200/JCO.2005.02.840. View

14.

Thunnissen E, Van der Oord K, den Bakker M . Prognostic and predictive biomarkers in lung cancer. A review. Virchows Arch. 2014; 464(3):347-58. DOI: 10.1007/s00428-014-1535-4. View

15.

Sequist L, Yang J, Yamamoto N, OByrne K, Hirsh V, Mok T . Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013; 31(27):3327-34. DOI: 10.1200/JCO.2012.44.2806. View

16.

Perez-Soler R . The role of erlotinib (Tarceva, OSI 774) in the treatment of non-small cell lung cancer. Clin Cancer Res. 2004; 10(12 Pt 2):4238s-4240s. DOI: 10.1158/1078-0432.CCR-040017. View

17.

Scagliotti G, Novello S, Schiller J, Hirsh V, Sequist L, Soria J . Rationale and design of MARQUEE: a phase III, randomized, double-blind study of tivantinib plus erlotinib versus placebo plus erlotinib in previously treated patients with locally advanced or metastatic, nonsquamous, non-small-cell lung cancer. Clin Lung Cancer. 2012; 13(5):391-5. DOI: 10.1016/j.cllc.2012.01.003. View

18.

Arteaga C . The epidermal growth factor receptor: from mutant oncogene in nonhuman cancers to therapeutic target in human neoplasia. J Clin Oncol. 2001; 19(18 Suppl):32S-40S. View

19.

Garassino M, Martelli O, Broggini M, Farina G, Veronese S, Rulli E . Erlotinib versus docetaxel as second-line treatment of patients with advanced non-small-cell lung cancer and wild-type EGFR tumours (TAILOR): a randomised controlled trial. Lancet Oncol. 2013; 14(10):981-8. DOI: 10.1016/S1470-2045(13)70310-3. View

20.

Paz-Ares L, Biesma B, Heigener D, von Pawel J, Eisen T, Bennouna J . Phase III, randomized, double-blind, placebo-controlled trial of gemcitabine/cisplatin alone or with sorafenib for the first-line treatment of advanced, nonsquamous non-small-cell lung cancer. J Clin Oncol. 2012; 30(25):3084-92. DOI: 10.1200/JCO.2011.39.7646. View