Hope or error: can combinations of EGFR tyrosine kinase inhibitors and other drugs replace monotherapy?


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

The development of targeted therapy over the past 20 years has undoubtedly changed the prognosis and course of some lung tumors. A significant increase in the frequency of objective responses, time on the background of therapy, as well as the total life expectancy of patients is an extremely important result of this stage. Nevertheless, the existence of a multitude of proven options raises many questions about the choice of the optimal treatment option based on the clinical characteristics of a particular patient. As part of this review, the authors wanted to remind the reader of the existing therapeutic options, as well as suggest possible options for a more personalized approach to the choice of therapy based on the data available in the literature.

Full Text

Restricted Access

About the authors

Fedor V. Moiseenko

Saint Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncological); N.N. Petrov National Medical Research Center of Oncology

Email: moiseenkofv@gmail.com
Dr. Sci. (Med.), Researcher at Department of Innovative Methods of Therapeutic Oncology and Rehabilitation, N.N. Petrov National Medical Research Center of Oncology; Head of the Oncological Chemotherapeutic (Anticancer Drug Therapy) Biotherapy Department, Saint Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncological) Saint Petersburg, Russia

References

  1. Mok T.S., Wu Y.L., Thongprasert S., et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361(10):947-57. Doi: 10.1056/ NEJMoa0810699.
  2. Imyanitov E.N., lyevleva A.G., Levchenko E.V. Molecular testing and targeted therapy for nonsmall cell lung cancer: Current status and perspectives. Crit Rev Oncol Hematol. 2021; 157:103194. Doi: 10.1016/j. critrevonc.2020.103194.
  3. Rosell R., Carcereny E., Gervais R., et al., Associazione Italiana Oncologia T 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. doi: 10.1016/S1470-2045(11)70393-X.
  4. Li X., Ren R., Ren S., et al. Peripheral blood for epidermal growth factor receptor mutation detection in non-small cell lung cancer patients. TranslOncol. 2014;7(3):341-48. Doi: 10.1016/j. tranon.2014.04.006
  5. Douillard J.Y, Ostoros G., Cobo M., et al. Gefitinib treatment in EGFR mutated caucasian NSCLC: circulating-free tumor DNA as a surrogate for determination of EGFR status. J Thorac Oncol. 2014;9(9):1345-53. Doi: 10.1097/ JTO.0000000000000263.
  6. Tseng J.S., Yang T.Y, Tsai C.R., et al. Dynamic plasma EGFR mutation status as a predictor of EGFR-TKI efficacy in patients with EGFR-mutant lung adenocarcinoma. J Thorac Oncol. 2015;10(4):603-10. Doi: 10.1097/ JTO.0000000000000443.
  7. Karachaliou N., Mayo-de las Casas C., Queralt C., et al., Spanish Lung Cancer G. Association of EGFR L858R Mutation in Circulating Free DNA With Survival in the EURTAC Trial. JAMA Oncol. 2015;1(2):149-57. Doi: 10.1001/ jamaoncol.2014.257.
  8. Yanagita M., Redig A.J., Paweletz C.P, et al. A Prospective Evaluation of Circulating Tumor Cells and Cell-Free DNA in EGFR-Mutant Non-Small Cell Lung Cancer Patients Treated with Erlotinib on a Phase II Trial. Clin Cancer Res. 2016;22(24):6010-doi: 10.1158/1078-0432.CCR-16-0909.
  9. Yang X., Zhuo M., Ye X., et al. Quantification of mutant alleles in circulating tumor DNA can predict survival in lung cancer. Oncotarget. 2016;7(15):20810-24. Doi: 10.18632/ oncotarget.8021.
  10. Lee Y., Park S., Kim W.S., et al. Correlation between progression-free survival, tumor burden, and circulating tumor DNA in the initial diagnosis of advanced-stage EGFR-mutated non-small cell lung cancer. Thorac Cancer. 2018;9(9):1104-10. doi: 10.1111/1759-7714.12793.
  11. Wu Y.L., Zhou C., Lu S., et al. Erlotinib versus gemcitabine/cisplatin in Chinese patients with EGFR mutation-positive advanced non-small-cell lung cancer: Crossover extension and post-hoc analysis of the ENSURE study. Lung Cancer. 2019;130:18-doi: 10.1016/j.lungcan.2019.01.016.
  12. Wu Y.L., Zhou C., Hu C.P, 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. Doi: 10.1016/ S1470-2045(13)70604-1.
  13. Kato T., Yoshioka H., Okamoto I., et al. Afatinibversus cisplatin plus pemetrexed in Japanese patients with advanced non-small cell lung cancer harboring activating EGFR mutations: Subgroup analysis of LUX-Lung 3. Cancer Sci. 2015;106(9):1202-11. doi: 10.1111/cas.12723.
  14. Park K., Tan E.H., O'Byrne K., 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-doi: 10.1016/S1470-2045(16)30033-X.
  15. Paz-Ares L., Tan E.H., O'Byrne K., 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):270-77. doi: 10.1093/annonc/mdw611.
  16. Yang J.C., Wu Y.L., Schuler M., 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. doi: 10.1016/S1470-2045(14)71173-8.
  17. Mok T.S., Cheng Y, Zhou X., 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(22):2244-50. Doi: 10.1200/ JCO.2018.78.7994.
  18. Ramalingam S.S., Vansteenkiste J., Planchard D., et al. Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC. N Engl J Med. 2020;382(1):41-50. Doi: 10.1056/ NEJMoa1913662.
  19. Mok T.S., Wu Y.L., Ahn M.J., et al. Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer. N Engl J Med. 2017;376(7):629-doi: 10.1056/NEJMoa1612674.
  20. Hochmair M.J., Morabito A., Hao D., et al. Sequential afatinib and osimertinib in patients with EGFR mutation-positive non-small-cell lung cancer: updated analysis of the observational GioTag study. Future Oncol. 2019;15(25):2905-doi: 10.2217/fon-2019-0346.
  21. Li R., Zhou X., Yao H., Li L. Four generations of EGFR TKIs associated with different pathogenic mutations in non-small cell lung carcinoma. J Drug Target. 2020;28(9):861-72. doi: 10.1080/1061186X.2020.1737934.
  22. He J., Zhou Z., Sun X., et al. The new opportunities in medicinal chemistry of fourth-generation EGFR inhibitors to overcome C797S mutation. Eur J Med Chem. 2021;210:112995. Doi: 10.1016/j. ejmech.2020.112995.
  23. Jia Y., Yun C. H., Park E., et al. Overcoming EGFR(T790M) and EGFR(C797S) resistance with mutant-selective allosteric inhibitors. Nature. 2016;534(7605):129-32. Doi: 10.1038/ nature17960.
  24. To C., Jang J., Chen T., et al. Single and Dual Targeting of Mutant EGFR with an Allosteric Inhibitor. Cancer Discov. 2019;9(7):926-43. doi: 10.1158/2159-8290.CD-18-0903.
  25. Li L., Jiang L., Wang Y, et al. Combination of Metformin and Gefitinib as First-Line Therapy for Nondiabetic Advanced NSCLC Patients with EGFR Mutations: A Randomized, Double-Blind Phase II Trial. Clin Cancer Res. 2019;25(23):6967-75. doi: 10.1158/1078-0432.CCR-19-0437.
  26. Sui X., Zhang M., Han X., et al. Combination of traditional Chinese medicine and epidermal growth factor receptor tyrosine kinase inhibitors in the treatment of non-small cell lung cancer: A systematic review and meta-analysis. Medicine (Baltimore). 2020;99(32):e20683. doi: 10.1097/MD.0000000000020683.
  27. Yang J.C., Cheng Y, Murakami H., et al. A Randomized Phase 2 Study of Gefitinib With or Without Pemetrexed as First-line Treatment in Nonsquamous NSCLC With EGFR Mutation: Final Overall Survival and Biomarker Analysis. J Thorac Oncol. 2020;15(1):91-100. Doi: 10.1016/j. jtho.2019.09.008.
  28. Han B., Jin B., Chu T., et al. Combination of chemotherapy and gefitinib as first-line treatment for patients with advanced lung adenocarcinoma and sensitive EGFR mutations: A randomized controlled trial. Int J Cancer. 2017;141(6):1249-56. doi: 10.1002/ijc.30806.
  29. Hosomi Y, Morita S., Sugawara S., et al. Gefitinib Alone Versus Gefitinib Plus Chemotherapy for Non-Small-Cell Lung Cancer With Mutated Epidermal Growth Factor Receptor: NEJ009 Study. J Clin Oncol. 2020;38:2:115-23. Doi: 10.1200/ JCO.19.01488.
  30. Xu L., Nilsson M.B., Saintigny P, et al. Epidermal growth factor receptor regulates MET levels and invasiveness through hypoxia-inducible factor-1alpha in non-small cell lung cancer cells. Oncogene. 2010;29:18:2616-27. Doi: 10.1038/ onc.2010.16.
  31. Tabernero J. The role of VEGF and EGFR inhibition: implications for combining anti-VEGF and anti-EGFR agents. Mol Cancer Res. 2007;(3):203-20. doi: 10.1158/1541-7786.MCR-06-0404.
  32. Larsen A.K., Ouaret D., El Ouadrani K., Petitprez A. Targeting EGFR and VEGF(R) pathway cross-talk in tumor survival and angiogenesis. Pharmacol Ther. 2011;131(1 ):80-90. Doi: 10.1016/j. pharmthera.2011.03.012.
  33. Le X., Nilsson M., Goldman J., et al. Dual EGFR- VEGF Pathway Inhibition: A Promising Strategy for Patients With EGFR-Mutant NSCLC. J Thorac Oncol. 2021;16(2):205-15. Doi: 10.1016/j. jtho.2020.10.006.
  34. Masuda C., Yanagisawa M., Yorozu K., et al. Bevacizumab counteracts VEGF-dependent resistance to erlotinib in an EGFR-mutated NSCLC xenograft model. Int J Oncol. 2017;51(2):425-doi: 10.3892/ijo.2017.4036.
  35. Saito H., Fukuhara T., Furuya N., et al. Erlotinib plus bevacizumab versus erlotinib alone in patients with EGFR-positive advanced non-squamous nonsmall-cell lung cancer (NEJ026): interim analysis of an open-label, randomised, multicentre, phase 3 trial. Lancet Oncol. 2019;20(5):625-35. doi: 10.1016/S1470-2045(19)30035-X.
  36. Nakagawa K., Garon E. B., Seto T., et al. Ramucirumab plus erlotinib in patients with untreated, EGFR-mutated, advanced non-small-cell lung cancer (RELAY): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20(12):1655-69. Doi: 10.1016/ S1470-2045(19)30634-5.
  37. Blakely C.M., Watkins T.B.K., Wu W., et al. Evolution and clinical impact of co-occurring genetic alterations in advanced-stage EGFR-mutant lung cancers. Nat Genet. 2017;49(12):1693-704. doi: 10.1038/ng.3990.
  38. Yu H.A., Suzawa K., Jordan E., et al. Concurrent Alterations in EGFR-Mutant Lung Cancers Associated with Resistance to EGFR Kinase Inhibitors and Characterization of MTOR as a Mediator of Resistance. Clin Cancer Res. 2018;24(13):3108-doi: 10.1158/1078-0432.CCR-17-2961.
  39. Jakobsen J.N., Santoni-Rugiu E., Grauslund M., et al. Concomitant driver mutations in advanced EGFR-mutated non-small-cell lung cancer and their impact on erlotinib treatment. Oncotarget. 2018;9(40):26195-208. Doi: 10.18632/ oncotarget.25490.
  40. Hong S., Gao F., Fu S., et al. Concomitant Genetic Alterations With Response to Treatment and Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Patients With EGFR-Mutant Advanced Non-Small Cell Lung Cancer. JAMA Oncol. 2018;4(5):739-42. Doi: 10.1001/ jamaoncol.2018.0049.
  41. Rachiglio A.M., Fenizia F, Piccirillo M.C., et al. The Presence of Concomitant Mutations Affects the Activity of EGFR Tyrosine Kinase Inhibitors in EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC) Patients. Cancers (Basel). 2019;11(3):341. doi: 10.3390/cancers11030341
  42. Bria E., Pilotto S., Amato E., et al. Molecular heterogeneity assessment by next-generation sequencing and response to gefitinib of EGFR mutant advanced lung adenocarcinoma. Oncotarget. 2015;6(14):12783-95. doi: 10.18632/oncotarget.3727.
  43. Lim S.M., Kim H.R., Cho E.K., et al. Targeted sequencing identifies genetic alterations that confer primary resistance to EGFR tyrosine kinase inhibitor (Korean Lung Cancer Consortium). Oncotarget. 2016;7(24):36311-320. doi: 10.18632/oncotarget.8904.
  44. Lee T., Lee B., Choi Y.L., et al. Non-small Cell Lung Cancer with Concomitant EGFR, KRAS, and ALK Mutation: Clinicopathologic Features of 12 Cases. J Pathol Transl Med. 2016;50(3):197-203. doi: 10.4132/jptm.2016.03.09.
  45. Oxnard G.R., Hu Y, Mileham K.F, et al. Assessment of Resistance Mechanisms and Clinical Implications in Patients With EGFR T790M-Positive Lung Cancer and Acquired Resistance to Osimertinib. JAMA Oncol. 2018;4(11):1527-34. Doi: 10.1001/ jamaoncol.2018.2969.
  46. Liu Y., Sun L., Xiong Z.C., et al. Meta-analysis of the impact of de novo and acquired EGFR T790M mutations on the prognosis of patients with nonsmall cell lung cancer receiving EGFR-TKIs. Onco Targets Ther. 2017;10:2267-79. Doi: 10.2147/ OTT.S133082.
  47. Testa U., Castelli G., Pelosi E. Lung Cancers: Molecular Characterization, Clonal Heterogeneity and Evolution, and Cancer Stem Cells. Cancers (Basel). 2018;10(8):248. Doi: 10.3390/ cancers10080248.
  48. Jamal-Hanjani M., Wilson G.A., McGranahan N., et al. Tracking the Evolution of Non-Small-Cell Lung Cancer. N Engl J Med. 2017;376(22):2109-21. doi: 10.1056/NEJMoa1616288.
  49. Robinson D.R., Wu Y. M., Lonigro R.J., et al. Integrative clinical genomics of metastatic cancer. Nature. 2017;548(7667):297-303. doi: 10.1038/nature23306.
  50. Kim E.S., Roy U.B., Ersek J.L., et al. Updates Regarding Biomarker Testing for Non-Small Cell Lung Cancer: Considerations from the National Lung Cancer Roundtable. J Thorac Oncol. 2019;14(3):338-42. Doi: 10.1016/j. jtho.2019.01.002.
  51. Canale M., Petracci E., Delmonte A., et al. Concomitant TP53 Mutation Confers Worse Prognosis in EGFR-Mutated Non-Small Cell Lung Cancer Patients Treated with TKIs. J Clin Med. 2020;9(4):1047. doi: 10.3390/jcm9041047
  52. Li X.M., Li W.F., Lin J.T., et al. Predictive and Prognostic Potential of TP53 in Patients With Advanced Non-Small-Cell Lung Cancer Treated With EGFR-TKI: Analysis of a Phase III Randomized Clinical Trial (CTONG 0901). Clin Lung Cancer. 2021;22(2):100-109.e3. Doi: 10.1016/j. cllc.2020.11.001.
  53. Imielinski M., Berger A., Hammerman P.S., et al. Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing. Cell. 2012;150(6):1107-20. Doi: 10.1016/j. cell.2012.08.029.
  54. Offin M., Chan J. M., Tenet M., et al. Concurrent RB1 and TP53 Alterations Define a Subset of EGFR-Mutant Lung Cancers at risk for Histologic Transformation and Inferior Clinical Outcomes. J Thorac Oncol. 2019;14(10):1784-93. doi: 10.1016/j.jtho.2019.06.002.
  55. Santoni-Rugiu E., Melchior L.C., Urbanska E.M., et al. Intrinsic resistance to EGFR-Tyrosine Kinase Inhibitors in EGFR-Mutant Non-Small Cell Lung Cancer: Differences and Similarities with Acquired Resistance. Cancers (Basel). 2019;11(7):923. doi: 10.3390/cancers11070923.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies