Erlotinib as Second-Line Therapy for Patients with Advanced Non-Small-Cell Lung Cancer and Wild-Type EGFR Tumors
Keywords:Non-small-cell lung carcinoma, EGFR, wild-type, erlotinib, second-line
Aim: The objective of the study was to determine the efficacy and safety of erlotinib in second-line therapy for patients with advanced non-small-cell lung carcinoma (NSCLC) and wild-type tumors, measuring progression-free survival (PFS), the response rate, and overall survival (OS).
Material and Methods: This retrospective, observational, and multicenter study involved 47 patients diagnosed with NSCLC and wild-type epidermal growth factor receptor(EGFR) who received erlotinib as second-line therapy in four Spanish hospitals. Primary and secondary endpoints included the determination of the efficacy (by measuring progression-free survival, PFS, the response rate, and overall survival, OS) and safety profile of erlotinib.
Results: The median PFS was 2.33 months (95% CI, 0.4-10.9). No differences in PFS were found regarding sex, age, smoking habits, ECOG performance status, and tumor histology. The median OS was 4.00 months (95% CI, 1.18-6.82). Four patients developed grade 3-4 non-hematological toxicities, including asthenia, cutaneous toxicity, and renal failure. One patient developed grade 3-4 thrombocytopenia.
Conclusion: Our study corroborates the modest but clear benefit of second-line agents, including erlotinib, for the treatment of advanced NSCLC, and supports their administration in patients with wild-type EGFR. Further prospective studies involving large number of patients are required to corroborate such results.
Crinò L, Weder W, van Meerbeeck J, Felip E; ESMO Guidelines Working Group. Early stage and locally advanced (non-metastatic) non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010; 21(Suppl): S103-15. http://dx.doi.org/10.1093/annonc/mdq207
Ettinger DS, Akerley W, Borghaei H, et al. Non-small cell lung cancer. J Natl Compr Canc Netw 2012; 10: 1236-1271.
Azzoli CG, Baker S Jr, Temin S, et al. American society of clinical oncology clinical practice guideline update on chemotherapy for stage IV non-small-cell lung cancer. J Clin Oncol 2009; 27: 6251-6266. http://dx.doi.org/10.1200/JCO.2009.23.5622
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. http://dx.doi.org/10.1056/NEJMoa011954
Caponi S, Vasile E, Ginocchi L, et al. Second-line treatment for non-small-cell lung cancer: one size does not fit all. Clin Lung Cancer 2010; 11:320-327. http://dx.doi.org/10.3816/CLC.2010.n.040
Hotta K, Fujiwara Y, Kiura K, et al. Relationship between response and survival in more than 50000 patients with advanced non-small cell lung cancer treated with systemic chemotherapy in 143 phase III trials. J Thorac Oncol 2007; 2: 402-407. http://dx.doi.org/10.1097/01.JTO.0000268673.95119.c7
Maione P, Rossi A, Bareschino MA, et al. Factors driving the choice of the best second-line treatment of advanced NSCLC. Rev Recent Clin Trials 2011; 6: 44-51. http://dx.doi.org/10.2174/157488711793980192
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: 2095-2103.
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: 1589-1597. http://dx.doi.org/10.1200/JCO.2004.08.163
Bezjak A, Tu D, Seymour L, et al. Symptom improvement in lung cancer patients treated with erlotinib: quality of life analysis of the National Cancer Institute of Canada Clinical Trials Group Study BR.21. J Clin Oncol 2006; 24: 3831-3837. http://dx.doi.org/10.1200/JCO.2006.05.8073
Reck M, van Zandwijk N, Gridelli C, et al. Erlotinib in advanced non-small cell lung cancer: efficacy and safety findings of the global phase IV Tarceva Lung Cancer Survival Treatment study. J Thorac Oncol 2010; 5: 1616-1622. http://dx.doi.org/10.1097/JTO.0b013e3181f1c7b0
da Cunha Santos G, Shepherd FA, Tsao MS. EGFR mutations and lung cancer. Annu Rev Pathol 2011; 6: 49-69. http://dx.doi.org/10.1146/annurev-pathol-011110-130206
D'Arcangelo M, Cappuzzo F. Erlotinib in the first-line treatment of non-small-cell lung cancer. Expert Rev Anticancer Ther 2013; 13: 523-533. http://dx.doi.org/10.1586/era.13.23
Yoshioka H, Hotta K, Kiura K, et al. A phase II trial of erlotinib monotherapy in pretreated patients with advanced non-small cell lung cancer who do not possess active EGFR mutations: Okayama Lung Cancer Study Group trial 0705. J Thorac Oncol 2010; 5: 99-104. http://dx.doi.org/10.1097/JTO.0b013e3181c20063
Garassino MC, Martelli O, Broggini M, et al. 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: 981-988. http://dx.doi.org/10.1016/S1470-2045(13)70310-3
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45: 228-247. http://dx.doi.org/10.1016/j.ejca.2008.10.026
American Joint Committee on Cancer. TNM classification of malignant tumours, lung, 7th edn. New York: Springer 2010. http://www.springer.com/us/book/9780387884400
Vázquez S, Lázaro M, Fírvida JL, et al. Second-line treatment in advanced non-small-cell lung cancer in the epidermal growth factor receptor wild-type population: review of patient profile. Anticancer Drugs 2014; 25: 368-374. http://dx.doi.org/10.1097/CAD.0000000000000066
Gao H, Ding X, Wei D, et al. Efficacy of erlotinib in patients with advanced non-small cell lung cancer: a pooled analysis of randomized trials. Anticancer Drugs 2011; 22: 842-852. http://dx.doi.org/10.1097/CAD.0b013e328349c303
Petrosyan F, Daw H, Haddad A, Spiro T. Targeted therapy for lung cancer. Anticancer Drugs 2012; 23: 1016-1021. http://dx.doi.org/10.1097/CAD.0b013e3283585149
Zhu CQ, da Cunha Santos G, Ding K, et al. Role of KRAS and EGFR as biomarkers of response to erlotinib in National Cancer Institute of Canada Clinical Trials Group Study BR.21. J Clin Oncol 2008; 26: 4268-4275. http://dx.doi.org/10.1200/JCO.2007.14.8924
Heigener DF, Wu YL, van Zandwijk N, Mali P, Horwood K, Reck M. Second-line erlotinib in patients with advanced non-small-cell lung cancer: subgroup analyses from theTRUST study. Lung Cancer 2011; 74: 274-279. http://dx.doi.org/10.1016/j.lungcan.2011.02.017
Ciuleanu T, Stelmakh L, Cicenas S, et al. Efficacy and safety of erlotinib versus chemotherapy in second-line treatment of patients with advanced, non-small-cell lung cancer with poor prognosis (TITAN): a randomised multicentre, open-label, phase 3 study. Lancet Oncol 2012; 13: 300-308. http://dx.doi.org/10.1016/S1470-2045(11)70385-0
Cappuzzo F, Ciuleanu T, Stelmakh L, et al. Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol 2010; 11: 521-529. http://dx.doi.org/10.1016/S1470-2045(10)70112-1
Brugger W, Triller N, Blasinska-Morawiec M, et al. Prospective molecular marker analyses of EGFR and KRAS from a randomized, placebo-controlled study of erlotinib maintenance therapy in advanced non-small-cell lung cancer. J Clin Oncol 2011; 29: 4113-4120. http://dx.doi.org/10.1200/JCO.2010.31.8162
Coudert B, Ciuleanu T, Park K, et al. Survival benefit with erlotinib maintenance therapy in patients with advanced non-small-cell lung cancer (NSCLC) according to response to first-line chemotherapy. Ann Oncol 2012; 23: 388-394. http://dx.doi.org/10.1093/annonc/mdr125
Karampeazis A, Voutsina A, Souglakos J, et al. Pemetrexed versus erlotinib in pretreated patients with advanced non-small cell lung cancer: a Hellenic Oncology Research Group (HORG) randomized phase 3 study. Cancer 2013; 119: 2754-2764. http://dx.doi.org/10.1002/cncr.28132
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. J Clin Oncol 2000; 18: 2354-2362.
Jazieh AR, Al Sudairy R, Abu-Shraie N, Al Suwairi W, Ferwana M, Murad MH. Erlotinib in wild type epidermal growth factor receptor non-small cell lung cancer: A systematic review. Ann Thorac Med 2013; 8: 204-208. http://dx.doi.org/10.4103/1817-1737.118503
Petrelli F, Borgonovo K, Cabiddu M, Barni S. Erlotinib as maintenance therapy in patients with advanced non-small cell lung cancer: a pooled analysis of three randomized trials. Anticancer Drugs 2011; 22: 1010-1019. http://dx.doi.org/10.1097/CAD.0b013e328349d80d