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The Patient - Patient-Centered Outcomes Research

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Open Access 01-02-2018 | Original Research Article

Does EGFR Mutation Type Influence Patient-Reported Outcomes in Patients with Advanced EGFR Mutation-Positive Non-Small-Cell Lung Cancer? Analysis of Two Large, Phase III Studies Comparing Afatinib with Chemotherapy (LUX-Lung 3 and LUX-Lung 6)

Authors: Yi-Long Wu, Vera Hirsh, Lecia V. Sequist, Cheng-Ping Hu, Jifeng Feng, Shun Lu, Yunchao Huang, Martin Schuler, Tony Mok, Nobuyuki Yamamoto, Kenneth O’Byrne, Sarayut L. Geater, Caicun Zhou, Dan Massey, Angela Märten, Juliane Lungershausen, James Chih-Hsin Yang

Published in: The Patient - Patient-Centered Outcomes Research | Issue 1/2018

Abstract

Introduction

In LUX-Lung 3 and LUX-Lung 6, afatinib significantly improved progression-free survival (PFS) versus chemotherapy in patients with tumors harboring common epidermal growth factor receptor (EGFR) mutations (Del19/L858R) and significantly improved overall survival (OS) in patients with tumors harboring Del19 mutations. Patient-reported outcomes stratified by EGFR mutation type are reported.

Patients and Methods

Lung cancer symptoms and health-related quality of life (QoL) were assessed every 21 days until progression using the EORTC Quality of Life Core Questionnaire C30 and its lung cancer-specific module, LC13. Analyses of cough, dyspnea, and pain were prespecified and included analysis of percentage of patients who improved on therapy, time to deterioration of symptoms, and change over time. Global health status (GHS)/QoL was also assessed. Analyses were conducted for all patients with tumors harboring Del19 or L858R mutations and were exploratory.

Results

Compared with chemotherapy, afatinib more commonly improved symptoms of, delayed time to deterioration for, and was associated with better mean scores over time for cough and dyspnea in patients with Del19 or L858R mutations. All three prespecified analyses of pain showed a trend favoring afatinib over chemotherapy. In both Del19 and L858R mutations, afatinib was also associated with improvements in GHS/QoL. Longitudinal analyses demonstrated statistically significant improvements in GHS/QoL for afatinib over chemotherapy for patients with tumors harboring Del19 mutations or L858R mutations.

Conclusions

These exploratory analyses suggest first-line afatinib improved lung cancer-related symptoms and GHS/QoL compared with chemotherapy in patients with non-small-cell lung cancer with tumors harboring common EGFR mutations, with benefits in both Del19 and L858R patients. When considered with OS (Del19 patients only) and PFS benefits, these findings substantiate the value of using afatinib over chemotherapy in these patient groups.

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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

Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, et al. 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;13(3):239–46. https://doi.org/10.1016/S1470-2045(11)70393-X.CrossRefPubMed

Sequist LV, Yang JC, Yamamoto N, O’Byrne K, Hirsh V, Mok T, et al. 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. https://doi.org/10.1200/JCO.2012.44.2806.CrossRefPubMed

Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol. 2010;11(2):121–8. https://doi.org/10.1016/S1470-2045(09)70364-X.CrossRefPubMed

Wu YL, Zhou C, Hu CP, Feng J, Lu S, Huang Y, et al. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol. 2014;15(2):213–22. https://doi.org/10.1016/S1470-2045(13)70604-1.CrossRefPubMed

Yang JC, Shih JY, Su WC, Hsia TC, Tsai CM, Ou SH, et al. Afatinib for patients with lung adenocarcinoma and epidermal growth factor receptor mutations (LUX-Lung 2): a phase 2 trial. Lancet Oncol. 2012;13(5):539–48. https://doi.org/10.1016/S1470-2045(12)70086-4.CrossRefPubMed

Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2011;12(8):735–42. https://doi.org/10.1016/S1470-2045(11)70184-X.CrossRefPubMed

Fukuoka M, Wu YL, Thongprasert S, Sunpaweravong P, Leong SS, Sriuranpong V, et al. Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). J Clin Oncol. 2011;29(21):2866–74. https://doi.org/10.1200/JCO.2010.33.4235.CrossRefPubMed

Okabe T, Okamoto I, Tamura K, Terashima M, Yoshida T, Satoh T, et al. Differential constitutive activation of the epidermal growth factor receptor in non-small cell lung cancer cells bearing EGFR gene mutation and amplification. Cancer Res. 2007;67(5):2046–53. https://doi.org/10.1158/0008-5472.CAN-06-3339.CrossRefPubMed

10.

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

11.

Han JY, Park K, Kim SW, Lee DH, Kim HY, Kim HT, et al. First-SIGNAL: first-line single-agent IRESSA versus gemcitabine and cisplatin trial in never-smokers with adenocarcinoma of the lung. J Clin Oncol. 2012;30(10):1122–8. https://doi.org/10.1200/JCO.2011.36.8456.CrossRefPubMed

12.

Inoue A, Kobayashi K, Maemondo M, Sugawara S, Oizumi S, Isobe H, et al. Updated overall survival results from a randomized phase III trial comparing gefitinib with carboplatin-paclitaxel for chemo-naive non-small cell lung cancer with sensitive EGFR gene mutations (NEJ002). Ann Oncol. 2013;24(1):54–9. https://doi.org/10.1093/annonc/mds214.CrossRefPubMed

13.

Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, et al. Final overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802). Ann Oncol. 2015;26(9):1877–83. https://doi.org/10.1093/annonc/mdv276.CrossRefPubMed

14.

Wu YL, Zhou C, Liam CK, Wu G, Liu X, Zhong Z, et al. First-line erlotinib versus gemcitabine/cisplatin in patients with advanced EGFR mutation-positive non-small-cell lung cancer: analyses from the phase III, randomized, open-label, ENSURE study. Ann Oncol. 2015;26(9):1883–9. https://doi.org/10.1093/annonc/mdv270.CrossRefPubMed

15.

Yoshioka H, Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I et al. Final overall survival results of WJTOG 3405, a randomized phase 3 trial comparing gefitinib (G) with cisplatin plus docetaxel (CD) as the first-line treatment for patients with non-small cell lung cancer (NSCLC) harboring mutations of the epidermal growth factor receptor (EGFR). ASCO Meeting Abstracts. 2014;32(15_suppl):8117.

16.

Lee C, Davies LC, Wu Y-L, Mitsudomi T, Inoue A, Rosell R et al. The impact on overall survival (OS) of first-line gefitinib (G) and erlotinib (E) and of clinical factors in advanced non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor mutations (EGFR mut) based on meta-analysis of 1,231 patients (pts) enrolled in 6 major randomized trials. ASCO Meeting Abstracts. 2015;33(15_suppl):8072.

17.

Yang JC, Wu YL, Schuler M, Sebastian M, Popat S, Yamamoto N, et al. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 2015;16(2):141–51. https://doi.org/10.1016/S1470-2045(14)71173-8.CrossRefPubMed

18.

Chen G, Feng J, Zhou C, Wu YL, Liu XQ, Wang C, et al. Quality of life (QoL) analyses from OPTIMAL (CTONG-0802), a phase III, randomised, open-label study of first-line erlotinib versus chemotherapy in patients with advanced EGFR mutation-positive non-small-cell lung cancer (NSCLC). Ann Oncol. 2013;24(6):1615–22. https://doi.org/10.1093/annonc/mdt012.CrossRefPubMed

19.

Oizumi S, Kobayashi K, Inoue A, Maemondo M, Sugawara S, Yoshizawa H, et al. Quality of life with gefitinib in patients with EGFR-mutated non-small cell lung cancer: quality of life analysis of North East Japan Study Group 002 Trial. Oncologist. 2012;17(6):863–70. https://doi.org/10.1634/theoncologist.2011-0426.CrossRefPubMedPubMedCentral

20.

Wu YL, Fukuoka M, Mok TS, Saijo N, Thongprasert S, Yang JC, et al. Tumor response and health-related quality of life in clinically selected patients from Asia with advanced non-small-cell lung cancer treated with first-line gefitinib: post hoc analyses from the IPASS study. Lung Cancer. 2013;81(2):280–7. https://doi.org/10.1016/j.lungcan.2013.03.004.CrossRefPubMed

21.

Yang JC, Hirsh V, Schuler M, Yamamoto N, O’Byrne KJ, Mok TS, et al. Symptom control and quality of life in LUX-Lung 3: a phase III study of afatinib or cisplatin/pemetrexed in patients with advanced lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013;31(27):3342–50. https://doi.org/10.1200/JCO.2012.46.1764.CrossRefPubMed

22.

Geater SL, Xu CR, Zhou C, Hu CP, Feng J, Lu S, et al. Symptom and quality of life improvement in LUX-Lung 6: an open-label phase III study of afatinib versus cisplatin/gemcitabine in Asian patients with EGFR mutation-positive advanced non-small-cell lung cancer. J Thorac Oncol. 2015;10(6):883–9. https://doi.org/10.1097/JTO.0000000000000517.CrossRefPubMed

23.

Fayers P, Aaronson N, Bjordal K, Groenvold M, Curran D, Bottomley A. EORTC QLQ-C30 scoring manual. 3rd ed. Brussels: EORTC; 2001.

24.

Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993;85(5):365–76.CrossRefPubMed

25.

Bergman B, Aaronson NK, Ahmedzai S, Kaasa S, Sullivan M. The EORTC QLQ-LC13: a modular supplement to the EORTC Core Quality of Life Questionnaire (QLQ-C30) for use in lung cancer clinical trials. EORTC Study Group on Quality of Life. Eur J Cancer. 1994;30A(5):635–42.CrossRefPubMed

26.

Earle CC, Weeks JC. The science of quality-of-life measurement in lung cancer. In: Lipscomb J, Gotay CC, Snyder C, editors. Outcomes assessment in cancer: measures, methods, and applications. Cambridge: Cambridge University Press; 2005.

27.

National Comprehensive Cancer Network. NCCN Guidelines: Non-Small Cell Lung Cancer. V 1. 2015. Available at: http://www.nccn.org/professionals/physician_gls/pdf/mcc.pdf.

28.

Reck M, Popat S, Reinmuth N, De Ruysscher D, Kerr KM, Peters S et al. Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25 Suppl 3:iii27-39. https://doi.org/10.1093/annonc/mdu199.

29.

Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010;362(25):2380–8. https://doi.org/10.1056/NEJMoa0909530.CrossRefPubMed

30.

Wu YL, Liam CK, Zhou C, et al. First-line erlotinib versus cisplatin/gemcitabine (GP) in patients with advanced EGFR mutation-positive non-small-cell lung cancer (NSCLC): interim analyses from the phase 3, open-label, ENSURE study. J Thorac Oncol. 2013;8(Suppl. 2):S603.

31.

Park K, Tan EH, O’Byrne K, Zhang L, Boyer M, Mok T, et al. Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial. Lancet Oncol. 2016;17(5):577–89. https://doi.org/10.1016/S1470-2045(16)30033-X.CrossRefPubMed

32.

Paz-Ares L, Tan EH, O’Byrne K, Zhang L, Hirsh V, Boyer M, et al. Afatinib versus gefitinib in patients with EGFR mutation-positive advanced non-small-cell lung cancer: overall survival data from the phase IIb LUX-Lung 7 trial. Ann Oncol. 2017;28(2):270–7. https://doi.org/10.1093/annonc/mdw611.CrossRefPubMedPubMedCentral

Title: Does EGFR Mutation Type Influence Patient-Reported Outcomes in Patients with Advanced EGFR Mutation-Positive Non-Small-Cell Lung Cancer? Analysis of Two Large, Phase III Studies Comparing Afatinib with Chemotherapy (LUX-Lung 3 and LUX-Lung 6)
Authors: Yi-Long Wu
Vera Hirsh
Lecia V. Sequist
Cheng-Ping Hu
Jifeng Feng
Shun Lu
Yunchao Huang
Martin Schuler
Tony Mok
Nobuyuki Yamamoto
Kenneth O’Byrne
Sarayut L. Geater
Caicun Zhou
Dan Massey
Angela Märten
Juliane Lungershausen
James Chih-Hsin Yang
Publication date: 01-02-2018
Publisher: Springer International Publishing
Published in: The Patient - Patient-Centered Outcomes Research / Issue 1/2018
Print ISSN: 1178-1653
Electronic ISSN: 1178-1661
DOI: https://doi.org/10.1007/s40271-017-0287-z

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