Targeted therapy of non-small cell lung cancer with rare EGFR gene mutations

Sukhoversha O.A.

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Publications
Targeted therapy of non-small cell lung cancer with rare EGFR gene mutations

June 25, 2021

937

Allergology and Pulmonology

Keywords :

non-small cell lung cancer

Specialities :

Allergology and Pulmonology

Oncology, Hematology

Resume

The treatment of choice for patients with EGFR mutation-positive non-small cell lung cancer (NSCLC) is an EGFR tyrosine kinase inhibitor (TKI). Most clinical trial data with these agents are limited to patients with the common activating EGFR mutations as follows: exon 19 deletions and exon 21 L858R point mutations. However, a significant proportion of patients with NSCLC harbor uncommon EGFR mutations that have variable sensitivity to different EGFR TKIs. Owing to its molecular structures, osimertinib has broader inhibitory profiles than the first-generation agents. Nevertheless, the paucity of prospective clinical data, the wide heterogeneity of uncommon mutations, and the existence of compound mutations often complicate treatment decisions in this patient subgroup. The following we collate clinical data on the efficacy of third generation TKIs, in particular osimertinib, in patients with NSCLC and rare or complex EGFR mutations. Particular attention is paid to the treatment of this subgroup of patients in the active phase of the COVID-19 disease, including the results of our own observations.

References:

1. Chen Z., Fillmore C.M., Hammerman P.S. et al. (2014) Non-small-cell lung cancers: a heterogeneous set of diseases. Nature reviews. Cancer, 14(8): 535–546. doi.org/10.1038/nrc3775.
2. Yarden Y., Sliwkowski M.X. (2001) Untangling the ErbB signalling network. Nature reviews. Molecular cell biology, 2(2): 127–137. doi.org/10.1038/35052073.
3. Gschwind A., Fischer O.M., Ullrich A. (2004) The discovery of receptor tyrosine kinases: targets for cancer therapy. Nature reviews. Cancer, 4(5): 361–370. doi.org/10.1038/nrc1360.
4. Burgess A.W. (2008) EGFR family: structure physiology signalling and therapeutic targets. Growth factors, 26(5): 263–274. doi.org/10.1080/08977190802312844.
5. Sabbah D.A., Hajjo R., Sweidan K. (2020) Review on Epidermal Growth Factor Receptor (EGFR) Structure, Signaling Pathways, Interactions, and Recent Updates of EGFR Inhibitors. Curr. Topics Med. Сhem., 20(10): 815–834. doi.org/10.2174/1568026620666200303123102.
6. Plönes T., Engel-Riedel W., Stoelben E. et al. (2016) Molecular Pathology and Personalized Medicine: The Dawn of a New Era in Companion Diagnostics-Practical Considerations about Companion Diagnostics for Non-Small-Cell-Lung-Cancer. J. Personal. Med., 6(1): 3. doi.org/10.3390/jpm6010003.
7. Wang D.D., Ma L., Wong M.P. et al. (2015) Contribution of EGFR and ErbB-3 Heterodimerization to the EGFR Mutation-Induced Gefitinib- and Erlotinib-Resistance in Non-Small-Cell Lung Carcinoma Treatments. PloS One, 10(5): e0128360. doi.org/10.1371/journal.pone.0128360.
8. Brambilla E., Gazdar A. (2009) Pathogenesis of lung cancer signalling pathways: roadmap for therapies. Eur. Resp. J., 33(6): 1485–1497. doi.org/10.1183/09031936.00014009.
9. El-Telbany А., Ma P. (2012) Cancer Genes in Lung Cancer. Genes Cancer, 3(7–8): 467–480.
10. Couraud S., Zalcman G., Milleron B. et al. (2012) Lung cancer in never smokers — a review. Eur. J. Cancer, 48(9): 1299–1311. doi.org/10.1016/j.ejca.2012.03.007.
11. Kosaka T., Yatabe Y., Endoh H. et al. (2004) Mutations of the epidermal growth factor receptor gene in lung cancer: biological and clinical implications. Cancer Res., 64(24): 8919–8923. doi.org/10.1158/0008–5472.CAN-04–2818.
12. Shparik Ya.V., Ponomareva O.V., Sokolov V.V. et al. (2020) Prevalence of EGFR gene mutations in Ukrainian patients with locally advanced or metastatic non-small cell lung cancer. Clin.Oncol., 10 (37–38): 10–17. (In Ukr.).
13. Lynch T.J., Bell D.W., Sordella R. et al. (2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. The New Engl. J. Med., 350(21): 2129–2139. doi.org/10.1056/NEJMoa040938.
14. Paez J.G., Jänne P.A., Lee J.C. et al. (2004) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science, 304(5676): 1497–1500. doi.org/10.1126/science.1099314.
15. Sharma S.V., Bell D.W., Settleman J., Haber D.A. (2007) Epidermal growth factor receptor mutations in lung cancer. Nature Reviews. Cancer, 7(3): 169–181. doi.org/10.1038/nrc2088.
16. Yatabe Y., Mitsudomi T. (2007) Epidermal growth factor receptor mutations in lung cancers. Pathol. Internat., 57(5): 233–244. doi.org/10.1111/j.1440–1827.2007.02098.x.
17. Yoneda K., Tanaka F. (2018) Molecular diagnosis and targeting for lung cancer. In: Molecular Diagnosis and Targeting for Thoracic and Gastrointestinal Malignancy. Y. Shimada, K. Yanaga (Eds.). Springer Nature Singapore, Singapore, 1–32.
18. Kobayashi Y., Mitsudomi T. (2016) Not all epidermal growth factor receptor mutations in lung cancer are created equal: Perspectives for individualized treatment strategy. Cancer Sci., 107(9): 1179–1186. doi.org/10.1111/cas.12996.
19. Saito M., Shiraishi K., Kunitoh H. et al. (2016) Gene aberrations for precision medicine against lung adenocarcinoma. Cancer Sci., 107(6): 713–720. doi.org/10.1111/cas.12941.
20. Siegelin M., Borczuk A. (2014) Epidermal growth factor receptor mutations in lung adenocarcinoma. Lab. Invest., 94: 129–137.
21. Masood A., Kancha R.K., Subramanian J. (2019) Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in non-small cell lung cancer harboring uncommon EGFR mutations: Focus on afatinib. In: Seminars in oncology, 46(3): 271–283.
22. Kim E.Y., Cho E.N., Park H.S. et al. (2016) Compound EGFR mutation is frequently detected with co-mutations of actionable genes and associated with poor clinical outcome in lung adenocarcinoma. Cancer Biol. Ther., 17(3): 237–245.
23. portal.gdc.cancer.gov
24. Shen Y.C., Tseng G.C., Tu C.Y. et al. (2017) Comparing the effects of afatinib with gefitinib or Erlotinib in patients with advanced-stage lung adenocarcinoma harboring non-classical epidermal growth factor receptor mutations. Lung Cancer, 110: 56–62.
25. Kuiper J.L., Hashemi S.M.S., Thunnissen E. et al. (2016) Non-classic EGFR mutations in a cohort of Dutch EGFR-mutated NSCLC patients and outcomes following EGFR-TKI treatment. Br. J. Cancer, 115(12): 1504–1512.
26. Krawczyk P., Kowalski D.M., Ramlau R. et al. (2017) Comparison of the effectiveness of erlotinib, gefitinib, and afatinib for treatment of non‑small cell lung cancer in patients with common and rare EGFR gene mutations. Oncol. Letters, 13(6): 4433–4444.
27. Gallant J.N., Sheehan J.H., Shaver T.M. et al. (2015) EGFR kinase domain duplication (EGFR-KDD) is a novel oncogenic driver in lung cancer that is clinically responsive to afatinib. Cancer Discov., 5(11): 1155–1163.
28. Konduri K., Gallant J.N., Chae Y.K. et al. (2016) EGFR fusions as novel therapeutic targets in lung cancer. Cancer Discov., 6(6): 601–611.
29. Kohsaka S., Nagano M., Ueno T. et al. (2017) A method of high-throughput functional evaluation of EGFR gene variants of unknown significance in cancer. Sci. Translat. Med., 9(416): 10.1126/scitranslmed.aan6566 pii:eaan6566.
30. Tsao M.S., Sakurada A., Cutz J.C. et al. (2005) Erlotinib in lung cancer — molecular and clinical predictors of outcome. New Engl. J. Med., 353(2): 133–144. doi.org/10.1056/NEJMoa050736.
31. Shaw A.T., Kim D.W., Nakagawa K. et al. (2013) Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. New Engl. J. Med., 368(25): 2385–2394. doi.org/10.1056/NEJMoa1214886.
32. Castellanos E., Feld E., Horn L. (2017) Driven by Mutations: The Predictive Value of Mutation Subtype in EGFR-Mutated Non-Small Cell Lung Cancer. J. Thor. Oncol., 12(4): 612–623. doi.org/10.1016/j.jtho.2016.12.014.
33. Jiang T., Zhou C. (2014) Clinical activity of the mutant-selective EGFR inhibitor AZD9291 in patients with EGFR inhibitor-resistant non-small cell lung cancer. Translat. Lung Cancer Res., 3(6): 370–372. doi.org/10.3978/j.issn.2218–6751.2014.08.02.
34. O’Kane G.M., Bradbury P.A., Feld R. et al. (2017) Uncommon EGFR mutations in advanced non-small cell lung cancer. Lung cancer (Amsterdam, Netherlands), 109: 137–144. doi.org/10.1016/j.lungcan.2017.04.016.
35. Yang J.C., Sequist L.V., Geater S.L. et al. (2015) Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol., 16: 830–838.
36. Yang J.C., Wu Y.L., Schuler M. et al. (2015) 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., 16: 141–151.
37. Qin Y., Jian H., Tong X. et al. (2020) Variability of EGFR exon 20 insertions in 24 468 Chinese lung cancer patients and their divergent responses to EGFR inhibitors. Mol. Oncol., 14(8): 1695–1704.
38. van Veggel B., Santos J.V.M.R., Hashemi S.M.S. et al. (2020) Osimertinib treatment for patients with EGFR exon 20 mutation positive non-small cell lung cancer. Lung Cancer, 141: 9–13.
39. Cho J.H., Lim S.H., An H.J. et al. (2020) Osimertinib for patients with non–small-cell lung cancer harboring uncommon EGFR mutations: a multicenter, open-label, phase II trial (KCSG-LU15–09). J. Clin. Oncol., 38(5): 488.
40. Piotrowska Z., Wang Y., Sequist L.V., Ramalingam S.S. (2020) ECOG-ACRIN 5162: A phase II study of osimertinib 160 mg in NSCLC with EGFR exon 20 insertions. J. Clin. Oncol., 38(15): 9513–9513.
41. Ji J., Aredo J.V., Piper-Vallillo A. et al. (2020) Osimertinib in non-small cell lung cancer (NSCLC) with atypical EGFR activating mutations: A retrospective multicenter study. J. Clin. Oncol., 38(15): 9570–9570.
42. Bie Y., Wang J., Xiong L. et al. (2021) Lung adenocarcinoma organoids harboring EGFR 19Del and L643V double mutations respond to osimertinib and gefitinib: A case report. Medicine, 100(11): e24793. doi.org/10.1097/MD.0000000000024793.
43. Okuno T., Arakawa S., Yoshida T., Ohe Y. (2020) Efficacy of osimertinib in a patient with leptomeningeal metastasis and EGFR uncommon S768I mutation. Lung Cancer, 143: 95–96.
44. Shan C.G., Wang H., Lin T. et al. (2021) A non-small cell lung cancer (NSCLC) patient with leptomeningeal metastasis harboring rare epidermal growth factor receptor (EGFR) mutations G719S and L861Q benefited from doubling dosage of osimertinib: a case report. Annals of palliative medicine, apm-20–2556. doi.org/10.21037/apm-20–2556.
45. Ma C., Zhang J., Tang D. et al. (2020) Tyrosine kinase inhibitors could be effective against non-small cell lung cancer brain metastases harboring uncommon EGFR mutations. Front. Oncol., 10: 224.
46. Stirling R.G., Chau C., Shareh A. et al. (2021) Recent Advances on the Role of EGFR Tyrosine Kinase Inhibitors in the Management of NSCLC With Uncommon, Non Exon 20 Insertions, EGFR Mutations. J. Thorac. Oncol., 16(5): 784–797.
47. Brown H., Vansteenkiste J., Nakagawa K. et al. (2018) MA15. 03 PD-L1 expression in untreated EGFRm advanced NSCLC and response to osimertinib and SoC EGFR-TKIs in the FLAURA trial. J. Thorac. Oncol., 13(10): 408.
48. Wang Z., Cheng Y., An T. et al. (2018) Detection of EGFR mutations in plasma circulating tumour DNA as a selection criterion for first-line gefitinib treatment in patients with advanced lung adenocarcinoma (BENEFIT): a phase 2, single-arm, multicentre clinical trial. The Lancet Resp. Med., 6(9): 681–690.
49. Lai G.G., Lim T.H., Lim J. et al. (2019) Clonal MET amplification as a determinant of tyrosine kinase inhibitor resistance in epidermal growth factor receptor-mutant non-small-cell lung cancer. J. Clin. Oncol., 37(11): 876–884.
50. Sequist L.V., Han J.Y., Ahn M.J. et al. (2020) Osimertinib plus savolitinib in patients with EGFR mutation-positive, MET-amplified, non-small-cell lung cancer after progression on EGFR tyrosine kinase inhibitors: interim results from a multicentre, open-label, phase 1b study. Lancet. Oncol., 21(3): 373–386. doi.org/10.1016/S1470-2045(19)30785-5.
51. Jänne P.A., Yang J.C.H., Kim D.W. et al. (2015) AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. New Engl. J. Med., 372(18): 1689–1699.
52. Peters M.L.B., Costa D.B., Rangachari D. (2017) Compound uncommon EGFR mutations in a patient with advanced NSCLC and durable response to sequential EGFR targeted therapies. J. Thorac. Oncol., 12(4): 35–36.
53. Qin B.D., Jiao X.D., Yuan L.Y. et al. (2018) The effectiveness of afatinib and osimertinib in a Chinese patient with advanced lung adenocarcinoma harboring a rare triple EGFR mutation (R670W/H835L/L833V): a case report and literature review. OncoTargets and therapy, 11: 4739.
54. Yang M., Tong X., Xu X. et al. (2018) Case report: osimertinib achieved remarkable and sustained disease control in an advanced non-small-cell lung cancer harboring EGFR H773L/V774M mutation complex. Lung Cancer, 121: 1–4.
55. Roeper J., Falk M., Chalaris-Rißmann A. et al. (2020) TP53 co-mutations in EGFR mutated patients in NSCLC stage IV: A strong predictive factor of ORR, PFS and OS in EGFR mt+ NSCLC. Oncotarget, 11(3): 250–264. doi.org/10.18632/oncotarget.27430.
56. Wao H., Mhaskar R., Kumar A. et al. (2013) Survival of patients with non-small cell lung cancer without treatment: a systematic review and meta-analysis. Syst. rev., 2(1): 1–11.
57. Calabrò L., Peters S., Soria J. C. et al. (2020) Challenges in lung cancer therapy during the COVID-19 pandemic. Lancet Resp. Med., 8(6): 542–544.
58. Dai M.Y., Liu D.B., Liu M. et al. (2020) Abstract CT406: Patients with cancer appear more vulnerable to SARS-COV-2: A multi-center study during the COVID-19 outbreak. Cancer Res., 80(16): 406. DOI: 10.1158/1538–7445.AM2020-CT406.
59. Horn L., Whisenant J.G., Torri V. et al. (2020) Thoracic Cancers International COVID-19 Collaboration (TERAVOLT): Impact of type of cancer therapy and COVID therapy on survival. J. Clin. Oncol., 38 (3818): LBA111.
60. Zhang L., Zhu F., Xie L. et al. (2020) Clinical characteristics of COVID-19-infected cancer patients: a retrospective case study in three hospitals within Wuhan, China. Ann. Oncol., 31(7): 894–901.
61. Liang W., Guan W., Chen R. et al. (2020) Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China. Lancet Oncol., 21(3): 335–337.
62. Rogado J., Pangua C., Serrano-Montero G. et al. (2020) Covid-19 and lung cancer: A greater fatality rate? Lung Cancer, 146: 19–22. doi.org/10.1016/j.lungcan.2020.05.034.
63. Addeo A., Obeid M., Friedlaender A. (2020) COVID-19 and lung cancer: risks, mechanisms and treatment interactions. J. Immunother. Cancer, 8(1): e000892. doi.org/10.1136/jitc-2020–000892.
64. Curigliano G., Banerjee S., Cervantes A. et al. (2020) Managing cancer patients during the COVID-19 pandemic: an ESMO multidisciplinary expert consensus. Ann. Oncol., 31(10): 1320–1335.
65. Kuderer N.M., Choueiri T.K., Shah D.P. et al. (2020) Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study. The Lancet, 395(10241): 1907–1918.
66. Chaft J.E., Oxnard G.R., Sima C.S. et al. (2011) Disease flare after tyrosine kinase inhibitor discontinuation in patients with EGFR-mutant lung cancer and acquired resistance to erlotinib or gefitinib: implications for clinical trial design. Clin. Cancer Res., 17(19): 6298–6303.
67. Weisberg E., Parent A., Yang P. L. et al. (2020) Repurposing of kinase inhibitors for treatment of COVID-19. Pharm. Res., 37(9): 1–29. doi.org/10.1007/s11095–020–02851–7.
68. Singh A.P., Berman A.T., Marmarelis M.E. et al. (2020) Management of lung cancer during the COVID-19 pandemic. JCO Oncol. Pract., 16(9): 579–586.
69. Soria J.C., Ohe Y., Vansteenkiste J. et al. (2018) Osimertinib in untreated EGFRmutated advanced non-small cell lung cancer. N. Engl. J. Med., 378: 113–25.
70. Magee D.E., Hird A.E., Klaassen Z. et al. (2020) Adverse event profile for immunotherapy agents compared with chemotherapy in solid organ tumors: a systematic review and meta-analysis of randomized clinical trials. Ann. Oncol., 31: 50–60.
71. Baburaj G., Thomas L., Rao M. (2021) Potential Drug Interactions of Repurposed COVID-19 Drugs with Lung Cancer Pharmacotherapies. Arch. Med. Res., 52(3): 261–269. doi.org/10.1016/j.arcmed.2020.11.006.