#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

First-line treatments in EGFR-mutated advanced non-small cell lung cancer: A network meta-analysis


Autoři: Hongwei Zhang aff001;  Jun Chen aff002;  Tingting Liu aff003;  Jun Dang aff001;  Guang Li aff001
Působiště autorů: Department of Radiation Oncology, The First Hospital of China Medical University, Shenyang, China aff001;  Department of Radiation Oncology, Shenyang Chest Hospital, Shenyang, China aff002;  Department of Radiation Oncology, Anshan Cancer Hospital, Anshan, China aff003
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0223530

Souhrn

Background

It remains unknown which is the optimal first-line treatment regimen for patients with advanced epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). We performed a network meta-analysis to address this important issue.

Methods

PubMed, Embase, Cochrane Library, Web of Science and major international scientific meetings were searched for relevant randomized controlled trials (RCTs). Progression-free survival (PFS) data was the primary outcome of interest, and overall survival (OS) and serious adverse events (SAEs) were the secondary outcomes of interests, reported as hazard ratio (HR) or odds ratio (OR) and 95% confidence intervals (CIs).

Results

25 RCTs with a total of 5005 patients randomized to receive seven treatments were included in the meta-analysis. Third-generation tyrosine kinase inhibitor (TKI) (osimertinib) and first-generation TKIs (F-TKIs) in combination with chemotherapy (F-TKIs+CT) were more effective than F-TKIs alone in terms of PFS (HR = 0.46, 95% CI: 0.22–0.93; P = 0.031 and HR = 0.62, 95% CI: 0.39–0.98; P = 0.041) and OS (HR = 0.63, 95% CI: 0.43–0.91; P = 0.014 and HR = 0.73, 95% CI: 0.57–0.92; P = 0.008). Second-generation TKIs (S-TKIs) showed significant OS advantage over F-TKIs (HR = 0.83, 95% CI: 0.70–0.99; P = 0.04). Based on treatment ranking in terms of PFS and OS, osimertinib had the highest probability of being the most effective treatment (89% and 86%) and with the best tolerability. F-TKIs+CT was ranked the second-most effective regimen, but with relatively high risk of SAEs.

Conclusions

Osimertinib seemed to be the most preferable first-line treatment in advanced EGFR-mutated NSCLC. However, limitations of the study including a single RCT investigating osimertinib and immature OS data need to be considered.

Klíčová slova:

Adverse events – Cancer treatment – Chemotherapy – Network analysis – Non-small cell lung cancer – Randomized controlled trials – Tyrosine kinase inhibitors


Zdroje

1. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Non-small cell lung cancer, version 2.2019 (November 21, 2018). Available from: https://www.nccn.org/professionals/physician_gls

2. De Marinis F, Ciardiello F, Baas P, Crinò L, Giaccone G, Grossi F, et al. 30 Immunotherapy in advanced NSCLC-from the 'tsunami' of therapeutic knowledge to a clinical practice algorithm: results from an international expert panel meeting of the Italian Association of Thoracic Oncology (AIOT). ESMO Open. 2018;3: e000298. doi: 10.1136/esmoopen-2017-000298 29942662

3. Reck M, Rabe KF. Precision diagnosis and treatment for advanced nonsmall- cell lung cancer. N Engl J Med. 2017;377: 849–861. doi: 10.1056/NEJMra1703413 28854088

4. Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, et al; North-East Japan Study Group. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010;362: 2380–2388. doi: 10.1056/NEJMoa0909530 20573926

5. Inoue A, Kobayashi K, Maemondo M, Sugawara S, Oizumi S, Isobe H, et al; North-East Japan Study Group. Updated overall survival results from a randomized phase III trial comparing gefitinib with carboplatin-paclitaxel for chemo-naïve non-small cell lung cancer with sensitive EGFR gene mutations (NEJ002). Ann Oncol. 2013;24: 54–59. doi: 10.1093/annonc/mds214 22967997

6. Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, et al; West Japan Oncology Group. 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: 121–128. doi: 10.1016/S1470-2045(09)70364-X 20022809

7. Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Seto T, et al. Updated overall survival results of WJTOG 3405, a randomized phase III trial comparing gefitinib (G) with cisplatin plus docetaxel (CD) as the first-line treatment for patients with non-small cell lung cancer harboring mutations of the epidermal growth factor receptor (EGFR). Journal of Clinical Oncology. 2012;30(15 SUPPL.1).

8. Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, et al; Spanish Lung Cancer Group in collaboration with Groupe Français de Pneumo-Cancérologie and Associazione Italiana Oncologia Toracica. 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: 239–246. doi: 10.1016/S1470-2045(11)70393-X 22285168

9. Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, et al. Erlotinib versus chemotherapy as firstline treatment for patients with advanced EGFR mutation-positive nonsmall-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, openlabel, randomised, phase 3 study. Lancet Oncol. 2011;12: 735–742. doi: 10.1016/S1470-2045(11)70184-X 21783417

10. 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: 1877–1883. doi: 10.1093/annonc/mdv276 26141208

11. 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: 577–589. doi: 10.1016/S1470-2045(16)30033-X 27083334

12. 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: 270–277. doi: 10.1093/annonc/mdw611 28426106

13. Wu YL, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, et al. Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial. Lancet Oncol. 2017;18: 1454–1466. doi: 10.1016/S1470-2045(17)30608-3 28958502

14. Mok TS, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, et al. Improvement in Overall Survival in a Randomized Study That Compared Dacomitinib With Gefitinib in Patients With Advanced Non-Small-Cell Lung Cancer and EGFR-Activating Mutations. J Clin Oncol. 2018;36: 2244–2250. doi: 10.1200/JCO.2018.78.7994 29864379

15. Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, et al; FLAURA Investigators. Osimertinib in untreated EGFRmutated advanced non-small-cell lung cancer. N Engl J Med. 2018;378: 113–125. doi: 10.1056/NEJMoa1713137 29151359

16. Wu YL, Lee JS, Thongprasert S, Yu CJ, Zhang L, Ladrera G, et al. Intercalated combination of chemotherapy and erlotinib for patients with advanced stage non-small-cell lung cancer (FASTACT-2): a randomised, double-blind trial. Lancet Oncol. 2013;14: 777–786. doi: 10.1016/S1470-2045(13)70254-7 23782814

17. Yu H, Zhang J, Wu X, Luo Z, Wang H, Sun S, et al. A phase II randomized trial evaluating gefitinib intercalated with pemetrexed/platinum chemotherapy or pemetrexed/platinum chemotherapy alone in unselected patients with advanced non-squamous non-small cell lung cancer. Cancer Biol Ther. 2014;15: 832–839. doi: 10.4161/cbt.28874 24755888

18. Cheng Y, Murakami H, Yang PC, He J, Nakagawa K, Kang JH, et al. Randomized Phase II Trial of Gefitinib With and Without Pemetrexed as First-Line Therapy in Patients With Advanced Nonsquamous Non-Small-Cell Lung Cancer With Activating Epidermal Growth Factor Receptor Mutations. J Clin Oncol. 2016;34: 3258–3266. doi: 10.1200/JCO.2016.66.9218 27507876

19. Nakamura A, Inoue A, Morita S, Hosomi Y, Kato T, Fukuhara T, et al. Phase III study comparing gefitinib monotherapy (G) to combination therapy with gefitinib, carboplatin, and pemetrexed (GCP) for untreated patients (pts) with advanced non-small cell lung cancer (NSCLC) with EGFR mutations (NEJ009). J Clin Oncol: 2018 American Society of Clinical Oncology, ASCO. 2018;36(SUPPL): abstr 9005.

20. Seto T, Kato T, Nishio M, Goto K, Atagi S, Hosomi Y, et al. Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-smallcell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study. Lancet Oncol. 2014;15: 1236–1244. doi: 10.1016/S1470-2045(14)70381-X 25175099

21. Yamamoto N, Seto T, Nishio M, Goto K, Okamoto I, Yamanaka T, et al. Erlotinib plus bevacizumab (EB) versus erlotinib alone (E) as first-line treatment for advanced EGFR mutationpositive non-squamous non-small-cell lung cancer (NSCLC): survival follow-up results of JO25567. J Clin Oncol: 2018 American Society of Clinical Oncology, ASCO. 2018;36(SUPPL): abstr 9007.

22. Furuya N, Fukuhara T, Saito H, Watanabe K, Sugawara S, Iwasawa S, et al. Phase III study comparing bevacizumab plus erlotinib to erlotinib in patients with untreated NSCLC harboring activating EGFR-mutations:NEJ026. J Clin Oncol: 2018 American Society of Clinical Oncology, ASCO. 2018;36(SUPPL): abstr 9006.

23. Lin JZ, Ma SK, Wu SX, Yu SH, Li XY. A network meta-analysis of nonsmall-cell lung cancer patients with an activating EGFR mutation: Should osimertinib be the first-line treatment? Medicine (Baltimore). 2018;97: e11569.

24. Batson S, Mitchell SA, Windisch R, Damonte E, Munk VC, Reguart N. Tyrosine kinase inhibitor combination therapy in first-line treatment of non-small-cell lung cancer: systematic review and network meta-analysis. Onco Targets Ther. 2017;10: 2473–2482. doi: 10.2147/OTT.S134382 28503070

25. 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: 2443–2450. doi: 10.1093/annonc/mdx359 28945850

26. Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg. 2010;8: 336–341. doi: 10.1016/j.ijsu.2010.02.007 20171303

27. Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med. 1998;17: 2815–234. doi: 10.1002/(sici)1097-0258(19981230)17:24<2815::aid-sim110>3.0.co;2-8 9921604

28. Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials. 2007; 8: 16. doi: 10.1186/1745-6215-8-16 17555582

29. Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomized trials. BMJ. 2011;343: d5928. doi: 10.1136/bmj.d5928 22008217

30. Gelman A, Rubin D. Inference from iterative simulation using multiple sequences. Statist Sci. 1992;7: 457–511.

31. Neupane B, Richer D, Bonner AJ, Kibret T, Beyene J. Network meta-analysis using R: a review of currently available automated packages. PLoS One. 2014;9: e115065. doi: 10.1371/journal.pone.0115065 25541687

32. Brooks S, Gelman A. General methods for monitoring convergence of iterative simulations. J Comput Graph Stat. 1998;7: 434–455.

33. van Valkenhoef G, Dias S, Ades AE, Welton NJ. Automated generation of node-splitting models for assessment of inconsistency in network meta-analysis. Res Synth Methods. 2016;7: 80–93. doi: 10.1002/jrsm.1167 26461181

34. Chaimani A, Higgins JP, Mavridis D, Spyridonos P, Salanti G. Graphical tools for network meta-analysis in STATA. PLoS One. 2013;8: e76654. doi: 10.1371/journal.pone.0076654 24098547

35. 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: 947–957. doi: 10.1056/NEJMoa0810699 19692680

36. 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: 2866–2874. doi: 10.1200/JCO.2010.33.4235 21670455

37. Gridelli C, Ciardiello F, Gallo C, Feld R, Butts C, Gebbia V, et al. First-line erlotinib followed by second-line cisplatin-gemcitabine chemotherapy in advanced non-small-cell lung cancer: the TORCH randomized trial. J Clin Oncol. 2012;30: 3002–3011. doi: 10.1200/JCO.2011.41.2056 22778317

38. Chen YM, Tsai CM, Fan WC, Shih JF, Liu SH, Wu CH, et al. Phase II randomized trial of erlotinib or vinorelbine in chemonaive, advanced, non-small cell lung cancer patients aged 70 years or older. J Thorac Oncol. 2012;7: 412–418. doi: 10.1097/JTO.0b013e31823a39e8 22157367

39. 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: 1883–1889. doi: 10.1093/annonc/mdv270 26105600

40. 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: 1122–1128. doi: 10.1200/JCO.2011.36.8456 22370314

41. 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: 3327–3334. doi: 10.1200/JCO.2012.44.2806 23816960

42. 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: 141–151. doi: 10.1016/S1470-2045(14)71173-8 25589191

43. 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: 213–222. doi: 10.1016/S1470-2045(13)70604-1 24439929

44. Hirsch FR, Kabbinavar F, Eisen T, Martins R, Schnell FM, Dziadziuszko R, et al. A randomized, phase II, biomarker-selected study comparing erlotinib to erlotinib intercalated with chemotherapy in first-line therapy for advanced non-small-cell lung cancer. J Clin Oncol. 2011;29: 3567–3573. doi: 10.1200/JCO.2010.34.4929 21825259

45. Jänne PA, Wang X, Socinski MA, Crawford J, Stinchcombe TE, Gu L, et al. Randomized phase II trial of erlotinib alone or with carboplatin and paclitaxel in patients who were never or light former smokers with advanced lung adenocarcinoma: CALGB 30406 trial. J Clin Oncol. 2012;30: 2063–2069. doi: 10.1200/JCO.2011.40.1315 22547605

46. Herbst RS, Prager D, Hermann R, Fehrenbacher L, Johnson BE, Sandler A, et al; TRIBUTE Investigator Group. 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: 5892–5899. doi: 10.1200/JCO.2005.02.840 16043829

47. Leighl NB, Rizvi NA, de Lima LG Jr, Arpornwirat W, Rudin CM, Chiappori AA, et al. Phase 2 Study of Erlotinib in Combination With Linsitinib (OSI-906) or Placebo in Chemotherapy-Naive Patients With Non-Small-Cell Lung Cancer and Activating Epidermal Growth Factor Receptor Mutations. Clin Lung Cancer. 2017;18: 34–42. doi: 10.1016/j.cllc.2016.07.007 27686971

48. Planchard D, Boyer MJ, Lee JS, Dechaphunkul A, Cheema PK, Takahashi T, et al. Postprogression Outcomes for Osimertinib versus Standard-of-care EGFR-TKI in patients with Previously Untreated EGFR-mutated Advanced Non-Small Cell Lung Cancer. Clin Cancer Res. 2019;25: 2058–2063. doi: 10.1158/1078-0432.CCR-18-3325 30659024


Článek vyšel v časopise

PLOS One


2019 Číslo 10
Nejčtenější tento týden
Nejčtenější v tomto čísle
Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

plice
INSIGHTS from European Respiratory Congress
nový kurz

Současné pohledy na riziko v parodontologii
Autoři: MUDr. Ladislav Korábek, CSc., MBA

Svět praktické medicíny 3/2024 (znalostní test z časopisu)

Kardiologické projevy hypereozinofilií
Autoři: prof. MUDr. Petr Němec, Ph.D.

Střevní příprava před kolonoskopií
Autoři: MUDr. Klára Kmochová, Ph.D.

Všechny kurzy
Kurzy Podcasty Doporučená témata Časopisy
Přihlášení
Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se

#ADS_BOTTOM_SCRIPTS#