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Erschienen in: Targeted Oncology 4/2017

15.06.2017 | Original Research Article

Acquired Resistance to Erlotinib in EGFR Mutation-Positive Lung Adenocarcinoma among Hispanics (CLICaP)

verfasst von: Andrés F. Cardona, Oscar Arrieta, Martín Ignacio Zapata, Leonardo Rojas, Beatriz Wills, Noemí Reguart, Niki Karachaliou, Hernán Carranza, Carlos Vargas, Jorge Otero, Pilar Archila, Claudio Martín, Luis Corrales, Mauricio Cuello, Carlos Ortiz, Luis E. Pino, Rafael Rosell, Zyanya Lucia Zatarain-Barrón, on behalf of CLICaP

Erschienen in: Targeted Oncology | Ausgabe 4/2017

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Abstract

Background

Lung cancer harboring epidermal growth factor receptor (EGFR) mutations and treated with EGFR tyrosine kinase inhibitors (TKIs) all eventually develop acquired resistance to the treatment, with half of the patients developing EGFR T790M resistance mutations.

Objective

The purpose of this study was to assess histological and clinical characteristics and survival outcomes in Hispanic EGFR mutated lung cancer patients after disease progression.

Patients and Methods

EGFR mutation-positive lung cancer patients (n = 34) with acquired resistance to the EGFR-TKI erlotinib were identified from 2011 to 2015. Post-progression tumor specimens were collected for molecular analysis. Post-progression interventions, response to treatment, and survival were assessed and compared among all patients and those with and without T790M mutations.

Results

Mean age was 59.4 ± 13.9 years, 65% were never-smokers, and 53% had a performance status 0–1. All patients received erlotinib as first-line treatment. Identified mutations included: 60% DelE19 (Del746–750) and 40% L858R. First-line erlotinib overall response rate (ORR) was 61.8% and progression free survival (PFS) was 16.8 months (95% CI: 13.7–19.9). Acquired resistance mutations identified were T790M mutation (47.1%); PI3K mutations (14.7%); EGFR amplification (14.7%); KRAS mutation (5.9%); MET amplification (8.8%); HER2 alterations (5.9%, deletions/insertions in e20); and SCLC transformation (2.9%). Of patients, 79.4% received treatment after progression. ORR for post-erlotinib treatment was 47.1% (CR 2/PR 14) and median PFS was 8.3 months (95% CI: 2.2–36.6). Median overall survival (OS) from treatment initiation was 32.9 months (95% CI: 30.4–35.3), and only the use of post-progression therapy affected OS in a multivariate analysis (p = 0.05).

Conclusions

Hispanic patients with acquired resistance to erlotinib continued to be sensitive to other treatments after progression. The proportion of T790M+ patients appears to be similar to that previously reported in Caucasians.
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Literatur
1.
Zurück zum Zitat Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 11 Lyon, France. http://globocan.iarc.fr. Accessed 27 Aug 2016. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 11 Lyon, France. http://​globocan.​iarc.​fr. Accessed 27 Aug 2016.
2.
Zurück zum Zitat Brambilla E, Travis WD. Lung cancer. In: Stewart BW, Wild CP, editors. World cancer report. Lyon: World Health Organization; 2014. Brambilla E, Travis WD. Lung cancer. In: Stewart BW, Wild CP, editors. World cancer report. Lyon: World Health Organization; 2014.
4.
Zurück zum Zitat Sakurada A, Shepherd FA, Tsao MS. Epidermal growth factor receptor tyrosine kinase inhibitors in lung cancer: impact of primary or secondary mutations. Clin Lung Cancer. 2006;7(Suppl 4):S138–44.CrossRefPubMed Sakurada A, Shepherd FA, Tsao MS. Epidermal growth factor receptor tyrosine kinase inhibitors in lung cancer: impact of primary or secondary mutations. Clin Lung Cancer. 2006;7(Suppl 4):S138–44.CrossRefPubMed
6.
Zurück zum Zitat Arrieta O, Cardona AF, Martin C, Mas-Lopez L, Corrales-Rodriguez L, Bramuglia G, et al. Updated frequency of EGFR and KRAS mutations in NonSmall-cell lung cancer in Latin America: the Latin-American Consortium for the investigation of lung cancer (CLICaP). J Thorac Oncol. 2015;10(5):838–43. doi:10.1097/JTO.0000000000000481.CrossRefPubMed Arrieta O, Cardona AF, Martin C, Mas-Lopez L, Corrales-Rodriguez L, Bramuglia G, et al. Updated frequency of EGFR and KRAS mutations in NonSmall-cell lung cancer in Latin America: the Latin-American Consortium for the investigation of lung cancer (CLICaP). J Thorac Oncol. 2015;10(5):838–43. doi:10.​1097/​JTO.​0000000000000481​.CrossRefPubMed
7.
Zurück zum Zitat Nicholson RI, Gee JM, Harper ME. EGFR and cancer prognosis. Eur J Cancer. 2001;37(Suppl 4):S9–15.CrossRefPubMed Nicholson RI, Gee JM, Harper ME. EGFR and cancer prognosis. Eur J Cancer. 2001;37(Suppl 4):S9–15.CrossRefPubMed
9.
10.
Zurück zum Zitat Kobayashi S, Boggon TJ, Dayaram T, Janne PA, Kocher O, Meyerson M, et al. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med. 2005;352(8):786–92. doi:10.1056/NEJMoa044238.CrossRefPubMed Kobayashi S, Boggon TJ, Dayaram T, Janne PA, Kocher O, Meyerson M, et al. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med. 2005;352(8):786–92. doi:10.​1056/​NEJMoa044238.CrossRefPubMed
12.
Zurück zum Zitat Arrieta O, Cardona AF, Corrales L, Campos-Parra AD, Sanchez-Reyes R, Amieva-Rivera E, et al. The impact of common and rare EGFR mutations in response to EGFR tyrosine kinase inhibitors and platinum-based chemotherapy in patients with non-small cell lung cancer. Lung Cancer. 2015;87(2):169–75. doi:10.1016/j.lungcan.2014.12.009.CrossRefPubMed Arrieta O, Cardona AF, Corrales L, Campos-Parra AD, Sanchez-Reyes R, Amieva-Rivera E, et al. The impact of common and rare EGFR mutations in response to EGFR tyrosine kinase inhibitors and platinum-based chemotherapy in patients with non-small cell lung cancer. Lung Cancer. 2015;87(2):169–75. doi:10.​1016/​j.​lungcan.​2014.​12.​009.CrossRefPubMed
15.
Zurück zum Zitat Goldstraw P, Crowley J, Chansky K, Giroux DJ, Groome PA, Rami-Porta R, et al. The IASLC lung cancer staging project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumours. J Thorac Oncol. 2007;2(8):706–14. doi:10.1097/JTO.0b013e31812f3c1a.CrossRefPubMed Goldstraw P, Crowley J, Chansky K, Giroux DJ, Groome PA, Rami-Porta R, et al. The IASLC lung cancer staging project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumours. J Thorac Oncol. 2007;2(8):706–14. doi:10.​1097/​JTO.​0b013e31812f3c1a​.CrossRefPubMed
20.
Zurück zum Zitat Hwang KE, Jung JW, Oh SJ, Park MJ, Shon YJ, Choi KH, et al. Transformation to small cell lung cancer as an acquired resistance mechanism in EGFR-mutant lung adenocarcinoma: a case report of complete response to etoposide and cisplatin. Tumori. 2015;101(3):e96–8. doi:10.5301/tj.5000276.PubMed Hwang KE, Jung JW, Oh SJ, Park MJ, Shon YJ, Choi KH, et al. Transformation to small cell lung cancer as an acquired resistance mechanism in EGFR-mutant lung adenocarcinoma: a case report of complete response to etoposide and cisplatin. Tumori. 2015;101(3):e96–8. doi:10.​5301/​tj.​5000276.PubMed
22.
Zurück zum Zitat Arrieta O, Ramirez-Tirado LA, Baez-Saldana R, Pena-Curiel O, Soca-Chafre G, Macedo-Perez EO. Different mutation profiles and clinical characteristics among Hispanic patients with non-small cell lung cancer could explain the “Hispanic paradox”. Lung Cancer. 2015;90(2):161–6. doi:10.1016/j.lungcan.2015.08.010.CrossRefPubMed Arrieta O, Ramirez-Tirado LA, Baez-Saldana R, Pena-Curiel O, Soca-Chafre G, Macedo-Perez EO. Different mutation profiles and clinical characteristics among Hispanic patients with non-small cell lung cancer could explain the “Hispanic paradox”. Lung Cancer. 2015;90(2):161–6. doi:10.​1016/​j.​lungcan.​2015.​08.​010.CrossRefPubMed
23.
Zurück zum Zitat Jackman D, Pao W, Riely GJ, Engelman JA, Kris MG, Janne PA, et al. Clinical definition of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. J Clin Oncol. 2010;28(2):357–60. doi:10.1200/JCO.2009.24.7049.CrossRefPubMed Jackman D, Pao W, Riely GJ, Engelman JA, Kris MG, Janne PA, et al. Clinical definition of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. J Clin Oncol. 2010;28(2):357–60. doi:10.​1200/​JCO.​2009.​24.​7049.CrossRefPubMed
27.
Zurück zum Zitat Ilie M, Hofman V, Long E, Bordone O, Selva E, Washetine K, et al. Current challenges for detection of circulating tumor cells and cell-free circulating nucleic acids, and their characterization in non-small cell lung carcinoma patients. What is the best blood substrate for personalized medicine? Ann Transl Med. 2014;2(11):107. doi:10.3978/j.issn.2305-5839.2014.08.11.PubMedPubMedCentral Ilie M, Hofman V, Long E, Bordone O, Selva E, Washetine K, et al. Current challenges for detection of circulating tumor cells and cell-free circulating nucleic acids, and their characterization in non-small cell lung carcinoma patients. What is the best blood substrate for personalized medicine? Ann Transl Med. 2014;2(11):107. doi:10.​3978/​j.​issn.​2305-5839.​2014.​08.​11.PubMedPubMedCentral
28.
Zurück zum Zitat Chen Q, Quan Q, Ding L, Hong X, Zhou N, Liang Y, et al. Continuation of epidermal growth factor receptor tyrosine kinase inhibitor treatment prolongs disease control in non-small-cell lung cancers with acquired resistance to EGFR tyrosine kinase inhibitors. Oncotarget. 2015;6(28):24904–11. doi:10.18632/oncotarget.4570.CrossRefPubMedPubMedCentral Chen Q, Quan Q, Ding L, Hong X, Zhou N, Liang Y, et al. Continuation of epidermal growth factor receptor tyrosine kinase inhibitor treatment prolongs disease control in non-small-cell lung cancers with acquired resistance to EGFR tyrosine kinase inhibitors. Oncotarget. 2015;6(28):24904–11. doi:10.​18632/​oncotarget.​4570.CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat Chen N, Fang W, Zhan J, Hong S, Tang Y, Kang S, et al. Upregulation of PD-L1 by EGFR activation mediates the immune escape in EGFR-driven NSCLC: implication for optional immune targeted therapy for NSCLC patients with EGFR mutation. J Thorac Oncol. 2015;10(6):910–23. doi:10.1097/JTO.0000000000000500.CrossRefPubMed Chen N, Fang W, Zhan J, Hong S, Tang Y, Kang S, et al. Upregulation of PD-L1 by EGFR activation mediates the immune escape in EGFR-driven NSCLC: implication for optional immune targeted therapy for NSCLC patients with EGFR mutation. J Thorac Oncol. 2015;10(6):910–23. doi:10.​1097/​JTO.​0000000000000500​.CrossRefPubMed
33.
Zurück zum Zitat Lin C, Chen X, Li M, Liu J, Qi X, Yang W, et al. Programmed death-ligand 1 expression predicts tyrosine kinase inhibitor response and better prognosis in a cohort of patients with epidermal growth factor receptor mutation-positive lung adenocarcinoma. Clin Lung Cancer. 2015;16(5):e25–35. doi:10.1016/j.cllc.2015.02.002.CrossRefPubMed Lin C, Chen X, Li M, Liu J, Qi X, Yang W, et al. Programmed death-ligand 1 expression predicts tyrosine kinase inhibitor response and better prognosis in a cohort of patients with epidermal growth factor receptor mutation-positive lung adenocarcinoma. Clin Lung Cancer. 2015;16(5):e25–35. doi:10.​1016/​j.​cllc.​2015.​02.​002.CrossRefPubMed
34.
Zurück zum Zitat Zhang Y, Wang L, Li Y, Pan Y, Wang R, Hu H, et al. Protein expression of programmed death 1 ligand 1 and ligand 2 independently predict poor prognosis in surgically resected lung adenocarcinoma. Onco Targets Ther. 2014;7:567–73. doi:10.2147/OTT.S59959.CrossRefPubMedPubMedCentral Zhang Y, Wang L, Li Y, Pan Y, Wang R, Hu H, et al. Protein expression of programmed death 1 ligand 1 and ligand 2 independently predict poor prognosis in surgically resected lung adenocarcinoma. Onco Targets Ther. 2014;7:567–73. doi:10.​2147/​OTT.​S59959.CrossRefPubMedPubMedCentral
35.
36.
Zurück zum Zitat Arrieta O, Anaya P, Morales-Oyarvide V, Ramirez-Tirado LA, Polanco AC. Cost-effectiveness analysis of EGFR mutation testing in patients with non-small cell lung cancer (NSCLC) with gefitinib or carboplatin-paclitaxel. Eur J Health Econ: HEPAC: Health Econ Prev Care. 2016;17(7):855–63. doi:10.1007/s10198-015-0726-5.CrossRef Arrieta O, Anaya P, Morales-Oyarvide V, Ramirez-Tirado LA, Polanco AC. Cost-effectiveness analysis of EGFR mutation testing in patients with non-small cell lung cancer (NSCLC) with gefitinib or carboplatin-paclitaxel. Eur J Health Econ: HEPAC: Health Econ Prev Care. 2016;17(7):855–63. doi:10.​1007/​s10198-015-0726-5.CrossRef
Metadaten
Titel
Acquired Resistance to Erlotinib in EGFR Mutation-Positive Lung Adenocarcinoma among Hispanics (CLICaP)
verfasst von
Andrés F. Cardona
Oscar Arrieta
Martín Ignacio Zapata
Leonardo Rojas
Beatriz Wills
Noemí Reguart
Niki Karachaliou
Hernán Carranza
Carlos Vargas
Jorge Otero
Pilar Archila
Claudio Martín
Luis Corrales
Mauricio Cuello
Carlos Ortiz
Luis E. Pino
Rafael Rosell
Zyanya Lucia Zatarain-Barrón
on behalf of CLICaP
Publikationsdatum
15.06.2017
Verlag
Springer International Publishing
Erschienen in
Targeted Oncology / Ausgabe 4/2017
Print ISSN: 1776-2596
Elektronische ISSN: 1776-260X
DOI
https://doi.org/10.1007/s11523-017-0497-2

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