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Targeted Oncology

Erschienen in:

03.06.2020 | Original Research Article

Clinical Factors Affecting the Response to Osimertinib in Non-Small Cell Lung Cancer Patients with An Acquired Epidermal Growth Factor Receptor T790M Mutation: A Long-Term Survival Analysis

verfasst von: Ya Chen, Shuyuan Wang, Bo Zhang, Yiming Zhao, Lele Zhang, Minjuan Hu, Wei Zhang, Baohui Han

Erschienen in: Targeted Oncology | Ausgabe 3/2020

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Abstract

Background

Osimertinib is a standard therapy for advanced non-small cell lung cancer (NSCLC) patients with an acquired epidermal growth factor receptor (EGFR) T790M mutation; however, the exploration of clinical characteristics that may affect prognosis and long-term survival is still lacking.

Objective

This retrospective study aimed to provide long-term survival data and explore meaningful prognostic factors in patients treated with osimertinib.

Patients and Methods

A total of 246 patients with acquired EGFR T790M mutation who were treated with osimertinib were included in this study. Progression-free survival (PFS), overall survival from osimertinib initiation (OS1), overall survival from diagnosis of advanced disease (OS), and possible prognostic clinical features were analyzed.

Results

The median PFS, OS1, and OS values were 12.17, 24.33, and 47.86 months, respectively. The median PFS of patients harboring EGFR exon 19 deletions/T790M (19del/T790M) and those harboring EGFR 21 L858R/T790M were 13.27 and 9.77 months (p = 0.001), respectively, while the median OS1 values were 25.03 and 18.30 months (p = 0.023), respectively; however, no significant difference was found in median OS (p = 0.060). Cox regression analysis revealed that coexisting mutation type and extrathoracic metastasis affected survival (PFS, OS1). In addition, gene biopsy specimen type (tissue or blood sample) was related to PFS (p = 0.032), which implied that liquid biopsy may be an independent poor prognostic factor.

Conclusions

This is the first reported survival analysis of osimertinib-treated Chinese patients, which indicates a median OS of 47.86 months. The EGFR T790M mutation is likely to coexist with 19del and indicate longer PFS and OS1 than EGFR 21 L858R/T790M. Additionally, the extrathoracic metastasis status and biopsy specimen type might also affect the survival of patients treated with osimertinib.

Global Burden of Disease Cancer Collaboration, Fitzmaurice C, Akinyemiju TF, Al Lami FH, Alam T, Alizadeh-Navaei R, et al. Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2016: A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncol. 2018;4(11):1553–68. https://doi.org/10.1001/jamaoncol.2018.2706.

Tan DS, Mok TS, Rebbeck TR. Cancer genomics: diversity and disparity across ethnicity and geography. J Clin Oncol. 2016;34(1):91–101. https://doi.org/10.1200/jco.2015.62.0096.CrossRefPubMed

Herbst RS, Morgensztern D, Boshoff C. The biology and management of non-small cell lung cancer. Nature. 2018;553(7689):446–54. https://doi.org/10.1038/nature25183.CrossRefPubMed

Liu L, Liu J, Shao D, Deng Q, Tang H, Liu Z, et al. Comprehensive genomic profiling of lung cancer using a validated panel to explore therapeutic targets in East Asian patients. Cancer Sci. 2017;108(12):2487–94. https://doi.org/10.1111/cas.13410.CrossRefPubMedPubMedCentral

Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361(10):947–57. https://doi.org/10.1056/NEJMoa0810699.CrossRefPubMed

Yu HA, Pao W. Targeted therapies: Afatinib—new therapy option for EGFR-mutant lung cancer. Nat Rev Clin Oncol. 2013;10(10):551–2. https://doi.org/10.1038/nrclinonc.2013.154.CrossRefPubMedPubMedCentral

Shi YK, Wang L, Han BH, Li W, Yu P, Liu YP, et al. First-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance therapy for patients with advanced EGFR mutation-positive lung adenocarcinoma (CONVINCE): a phase 3, open-label, randomized study. Ann Oncol. 2017;28(10):2443–500. https://doi.org/10.1093/annonc/mdx359.CrossRefPubMed

Li D, Ambrogio L, Shimamura T, Kubo S, Takahashi M, Chirieac LR, et al. BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene. 2008;27(34):4702–11. https://doi.org/10.1038/onc.2008.109.CrossRefPubMedPubMedCentral

Pao W, Miller VA, Politi KA, Riely GJ, Somwar R, Zakowski MF, et al. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med. 2005;2(3):e73. https://doi.org/10.1371/journal.pmed.0020073.CrossRefPubMedPubMedCentral

10.

Yu HA, Arcila ME, Rekhtman N, Sima CS, Zakowski MF, Pao W, et al. Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers. Clin Cancer Res. 2013;19(8):2240–7. https://doi.org/10.1158/1078-0432.Ccr-12-2246.CrossRefPubMedPubMedCentral

11.

Tanaka K, Nosaki K, Otsubo K, Azuma K, Sakata S, Ouchi H, et al. Acquisition of the T790M resistance mutation during afatinib treatment in EGFR tyrosine kinase inhibitor-naive patients with non-small cell lung cancer harboring EGFR mutations. Oncotarget. 2017;8(40):68123–30. https://doi.org/10.18632/oncotarget.19243.CrossRefPubMedPubMedCentral

12.

Yang JC, Ahn MJ, Kim DW, Ramalingam SS, Sequist LV, Su WC, et al. Osimertinib in pretreated T790M-positive advanced non-small-cell lung cancer: AURA Study Phase II extension component. J Clin Oncol. 2017;35(12):1288–96. https://doi.org/10.1200/jco.2016.70.3223.CrossRefPubMed

13.

Yoon BW, Kim JH, Lee SH, Choi CM, Rho JK, Yoon S, et al. Comparison of T790M acquisition between patients treated with afatinib and gefitinib as first-line therapy: retrospective propensity score matching analysis. Transl Oncol. 2019;12(6):852–8. https://doi.org/10.1016/j.tranon.2019.04.004.CrossRefPubMedPubMedCentral

14.

Wu SG, Liu YN, Tsai MF, Chang YL, Yu CJ, Yang PC, et al. The mechanism of acquired resistance to irreversible EGFR tyrosine kinase inhibitor-afatinib in lung adenocarcinoma patients. Oncotarget. 2016;7(11):12404–13. https://doi.org/10.18632/oncotarget.7189.CrossRefPubMedPubMedCentral

15.

Janjigian YY, Smit EF, Groen HJ, Horn L, Gettinger S, Camidge DR, et al. Dual inhibition of EGFR with afatinib and cetuximab in kinase inhibitor-resistant EGFR-mutant lung cancer with and without T790M mutations. Cancer Discov. 2014;4(9):1036–45. https://doi.org/10.1158/2159-8290.Cd-14-0326.CrossRefPubMedPubMedCentral

16.

Ercan D, Zejnullahu K, Yonesaka K, Xiao Y, Capelletti M, Rogers A, et al. Amplification of EGFR T790M causes resistance to an irreversible EGFR inhibitor. Oncogene. 2010;29(16):2346–56. https://doi.org/10.1038/onc.2009.526.CrossRefPubMedPubMedCentral

17.

Kobayashi Y, Fujino T, Nishino M, Koga T, Chiba M, Sesumi Y, et al. EGFR T790M and C797S mutations as mechanisms of acquired resistance to dacomitinib. J Thorac Oncol. 2018;13(5):727–31. https://doi.org/10.1016/j.jtho.2018.01.009.CrossRefPubMed

18.

Cross DA, Ashton SE, Ghiorghiu S, Eberlein C, Nebhan CA, Spitzler PJ, et al. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 2014;4(9):1046–61. https://doi.org/10.1158/2159-8290.Cd-14-0337.CrossRefPubMedPubMedCentral

19.

Ahn MJ, Tsai CM, Shepherd FA, Bazhenova L, Sequist LV, Hida T, et al. Osimertinib in patients with T790M mutation-positive, advanced non-small cell lung cancer: Long-term follow-up from a pooled analysis of 2 phase 2 studies. Cancer. 2019;125(6):892–901. https://doi.org/10.1002/cncr.31891.CrossRefPubMed

20.

Mok TS, Wu YL, Ahn MJ, Garassino MC, Kim HR, Ramalingam SS, et al. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med. 2017;376(7):629–40. https://doi.org/10.1056/NEJMoa1612674.CrossRefPubMed

21.

Akamatsu H, Katakami N, Okamoto I, Kato T, Kim YH, Imamura F, et al. Osimertinib in Japanese patients with EGFR T790M mutation-positive advanced non-small-cell lung cancer: AURA3 trial. Cancer Sci. 2018;109(6):1930–8. https://doi.org/10.1111/cas.13623.CrossRefPubMedPubMedCentral

22.

Kiura K, Yoh K, Katakami N, Nogami N, Kasahara K, Takahashi T, et al. Osimertinib in patients with epidermal growth factor receptor T790M advanced non-small cell lung cancer selected using cytology samples. Cancer Sci. 2018;109(4):1177–84. https://doi.org/10.1111/cas.13511.CrossRefPubMedPubMedCentral

23.

Auliac JB, Perol M, Planchard D, Monnet I, Wislez M, Doubre H, et al. Real-life efficacy of osimertinib in pretreated patients with advanced non-small cell lung cancer harboring EGFR T790M mutation. Lung Cancer. 2019;127:96–102. https://doi.org/10.1016/j.lungcan.2018.11.037.CrossRefPubMed

24.

de Marinis F, Wu YL, de Castro G, Jr CGC, Chen YM, Cho BC, et al. ASTRIS: a global real-world study of osimertinib in %3e3000 patients with EGFR T790M positive non-small-cell lung cancer. Future Oncol. 2019;15(26):3003–144. https://doi.org/10.2217/fon-2019-0324.

25.

Oh DK, Ji WJ, Kim WS, Choi CM, Yoon SK, Rho JK, et al. Efficacy, safety, and resistance profile of osimertinib in T790M mutation-positive non-small cell lung cancer in real-world practice. PLoS ONE. 2019;14(1):e0210225. https://doi.org/10.1371/journal.pone.0210225.CrossRefPubMedPubMedCentral

26.

Ramalingam SS, Vansteenkiste J, Planchard D, Cho BC, Gray JE, Ohe Y, et al. Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. N Engl J Med. 2020;382(1):41–50. https://doi.org/10.1056/NEJMoa1913662.CrossRefPubMed

27.

Gelatti ACZ, Drilon A, Santini FC. Optimizing the sequencing of tyrosine kinase inhibitors (TKIs) in epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). Lung Cancer. 2019;137:113–22. https://doi.org/10.1016/j.lungcan.2019.09.017.CrossRefPubMed

28.

Roeper J, Falk M, Schatz S, Tiemann M, Wesseler C, Wiest GH, et al. Treatment patterns of EGFR mt+ NSCLC IV pts: real world data of the NOWEL network. Ann. Oncol. 2019;30(Suppl 5):v630. https://doi.org/10.1093/annonc/mdz260.055.

29.

Shah R, Girard N, Nagar SP, Griesinger F, Roeper J, Davis K, et al. Real-world (RW) treatment patterns and outcomes for second-line (2L) therapy and beyond in patients (pts) with epidermal growth factor receptor-mutated (EGFRm) advanced NSCLC receiving a first-line (1L) first- or second-generation (1G/2G) EGFR tyrosine kinase inhibitor (TKI). Ann Oncol. 2019;30(Suppl 5):v624–v625625. https://doi.org/10.1093/annonc/mdz260.044.CrossRef

30.

Goss G, Tsai C-M, Shepherd FA, Bazhenova L, Lee JS, Chang G-C, et al. Osimertinib for pretreated EGFR Thr790Met-positive advanced non-small-cell lung cancer (AURA2): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2016;17(12):1643–52. https://doi.org/10.1016/s1470-2045(16)30508-3.CrossRefPubMed

31.

Ke EE, Zhou Q, Zhang QY, Su J, Chen ZH, Zhang XC, et al. A higher proportion of the EGFR T790M mutation may contribute to the better survival of patients with Exon 19 deletions compared with those with L858R. J Thorac Oncol. 2017;12(9):1368–75. https://doi.org/10.1016/j.jtho.2017.05.018.CrossRefPubMed

32.

Lee CK, Wu YL, Ding PN, Lord SJ, Inoue A, Zhou C, et al. Impact of specific epidermal growth factor receptor (EGFR) mutations and clinical characteristics on outcomes after treatment with EGFR tyrosine kinase inhibitors versus chemotherapy in EGFR-mutant lung cancer: a meta-analysis. J Clin Oncol. 2015;33(17):1958–65. https://doi.org/10.1200/JCO.2014.58.1736.CrossRefPubMed

33.

Sun JM, Won YW, Kim ST, Kim JH, Choi YL, Lee J, et al. The different efficacy of gefitinib or erlotinib according to epidermal growth factor receptor exon 19 and exon 21 mutations in Korean non-small cell lung cancer patients. J Cancer Res Clin Oncol. 2011;137(4):687–94. https://doi.org/10.1007/s00432-010-0928-2.CrossRefPubMed

34.

Koyama N, Watanabe Y, Iwai Y, Kawamura R, Miwa C, Nagai Y, et al. Distinct benefit of overall survival between patients with non-small-cell lung cancer harboring EGFR Exon 19 deletion and Exon 21 L858R substitution. Chemotherapy. 2017;62(3):151–8. https://doi.org/10.1159/000454944.CrossRefPubMed

35.

Wang H, Huang J, Yu X, Han S, Yan X, Sun S, et al. Different efficacy of EGFR tyrosine kinase inhibitors and prognosis in patients with subtypes of EGFR-mutated advanced non-small cell lung cancer: a meta-analysis. J Cancer Res Clin Oncol. 2014;140(11):1901–9. https://doi.org/10.1007/s00432-014-1709-0.CrossRefPubMedPubMedCentral

36.

Furuyama K, Harada T, Iwama E, Shiraishi Y, Okamura K, Ijichi K, et al. Sensitivity and kinase activity of epidermal growth factor receptor (EGFR) exon 19 and others to EGFR-tyrosine kinase inhibitors. Cancer Sci. 2013;104(5):584–9. https://doi.org/10.1111/cas.12125.CrossRefPubMedPubMedCentral

37.

Zhu JQ, Zhong WZ, Zhang GC, Li R, Zhang XC, Guo AL, et al. Better survival with EGFR exon 19 than exon 21 mutations in gefitinib-treated non-small cell lung cancer patients is due to differential inhibition of downstream signals. Cancer Lett. 2008;265(2):307–17. https://doi.org/10.1016/j.canlet.2008.02.064.CrossRefPubMed

38.

Oxnard GR, Thress KS, Alden RS, Lawrance R, Paweletz CP, Cantarini M, et al. Association between plasma genotyping and outcomes of treatment with osimertinib (AZD9291) in advanced non-small-cell lung cancer. J Clin Oncol. 2016;34(28):3375–82. https://doi.org/10.1200/JCO.2016.66.7162.CrossRefPubMedPubMedCentral

Titel: Clinical Factors Affecting the Response to Osimertinib in Non-Small Cell Lung Cancer Patients with An Acquired Epidermal Growth Factor Receptor T790M Mutation: A Long-Term Survival Analysis
verfasst von: Ya Chen
Shuyuan Wang
Bo Zhang
Yiming Zhao
Lele Zhang
Minjuan Hu
Wei Zhang
Baohui Han
Publikationsdatum: 03.06.2020
Verlag: Springer International Publishing
Erschienen in: Targeted Oncology / Ausgabe 3/2020
Print ISSN: 1776-2596
Elektronische ISSN: 1776-260X
DOI: https://doi.org/10.1007/s11523-020-00724-y

Springer Medizin

Clinical Factors Affecting the Response to Osimertinib in Non-Small Cell Lung Cancer Patients with An Acquired Epidermal Growth Factor Receptor T790M Mutation: A Long-Term Survival Analysis