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Aumolertinib: A Review in Non-Small Cell Lung Cancer

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Abstract

Aumolertinib (formerly almonertinib; Ameile®) is an oral, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (EGFR-TKI) that is selective for mutant EGFR over wild-type EGFR. It has been developed for the treatment of advanced EGFR mutation-positive non-small cell lung cancer (NSCLC). In the phase 3 AENEAS trial conducted in Chinese patients, aumolertinib as first-line treatment significantly prolonged progression-free survival (PFS) and duration of response (DoR) compared with gefitinib in patients with advanced EGFR mutation-positive NSCLC; overall survival (OS) data from this study are immature. In the phase 1/2 APOLLO trial, aumolertinib showed good clinical activity (based on objective response rate, PFS, DoR and OS) in Chinese patients with locally advanced or metastatic EGFR T790M mutation-positive NSCLC who had progressed on or after prior EGFR-TKI therapy. Aumolertinib has a generally manageable tolerability profile; adverse events associated with wild-type EGFR inhibition (e.g. rash and diarrhoea) were less frequent with aumolertinib than gefitinib in AENEAS. Thus, aumolertinib is a promising new option for both first-line and second-line treatment in patients with advanced EGFR mutation-positive NSCLC.

Plain Language Summary

Non-small cell lung cancer (NSCLC), the most common type of lung cancer, is associated with a poor prognosis. In up to 50% of Asian patients and ≈ 17% of Caucasian patients with NSCLC, specific mutations in the epidermal growth factor receptor (EGFR) gene are responsible for tumour growth. Drugs that block the effects of EGFR [known as EGFR tyrosine kinase inhibitors (EGFR-TKIs)] improve survival in patients with NSCLC and EGFR mutations. Aumolertinib (Ameile®) is a third-generation EGFR-TKI that has been developed in China. When given to patients with previously untreated, advanced EGFR mutation-positive NSCLC, aumolertinib delayed cancer progression by ≈ 9 months compared with gefitinib, a first-generation EGFR-TKI. Aumolertinib also showed good clinical activity as a second-line treatment in patients with advanced EGFR mutation-positive NSCLC who had developed resistance during or after treatment with earlier-generation EGFR-TKIs. Overall, the tolerability profile of aumolertinib was similar to that of gefitinib, with some adverse events such as rash and diarrhoea being less frequent. Aumolertinib is a promising new first- or second-line treatment option in patients with advanced EGFR mutation-positive NSCLC.

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References

  1. Sequist LV. First-generation epidermal growth factor receptor tyrosine kinase inhibitors in EGFR mutation positive non-small cell lung cancer patients. J Thorac Oncol. 2008;3(Suppl 2):S143–5.

    Article  PubMed  Google Scholar 

  2. Zhao Y, Liu J, Cai X, et al. Efficacy and safety of first line treatments for patients with advanced epidermal growth factor receptor mutated, non-small cell lung cancer: systematic review and network meta-analysis. BMJ. 2019;367:I5460.

    Article  Google Scholar 

  3. Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361(10):947–57.

    Article  CAS  PubMed  Google Scholar 

  4. Rosell R, Carcereny E, Gervais R, 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.

    Article  CAS  PubMed  Google Scholar 

  5. Yu HA, Arcila ME, Rekhtman N, 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Yu HA, Riely GJ. Second-generation epidermal growth factor receptor tyrosine kinase inhibitors in lung cancers. J Natl Compr Canc Netw. 2013;11(2):161–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Pao W, Miller VA, Politi KA, 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.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Robichaux JP, Le X, Vijayan RSK, et al. Structure-based classification predicts drug response in EGFR-mutant NSCLC. Nature. 2021;597(7878):732–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Sullivan I, Planchard D. Next-generation EGFR tyrosine kinase inhibitors for treating EGFR-mutant lung cancer beyond first line. Front Med (Lausanne). 2016;3:76.

    PubMed  Google Scholar 

  10. Zhang H. Three generations of epidermal growth factor receptor tyrosine kinase inhibitors developed to revolutionize the therapy of lung cancer. Drug Des Dev Ther. 2016;10:3867–72.

    Article  CAS  Google Scholar 

  11. Mok TS, 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.

    Article  CAS  PubMed  Google Scholar 

  12. Sequist LV, Yang JC, Yamamoto N, 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.

    Article  CAS  PubMed  Google Scholar 

  13. Lamb YN, Scott LJ. Osimertinib: a review in T790M-positive advanced non-small cell lung cancer. Target Oncol. 2017;12(4):555–62.

    Article  PubMed  Google Scholar 

  14. Nagasaka M, Zhu VW, Lim SM, et al. Beyond osimertinib: the development of third-generation EGFR tyrosine kinase inhibitors for advanced EGFR+ NSCLC. J Thorac Oncol. 2021;16(5):740–63.

    Article  CAS  PubMed  Google Scholar 

  15. Ramalingam SS, 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.

    Article  CAS  PubMed  Google Scholar 

  16. Soria JC, Ohe Y, Vansteenkiste J, et al. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018;378(2):113–25.

    Article  CAS  PubMed  Google Scholar 

  17. Murtuza A, Bulbul A, Shen JP, et al. Novel third-generation EGFR tyrosine kinase inhibitors and strategies to overcome therapeutic resistance in lung cancer. Cancer Res. 2019;79(4):689–98.

    Article  CAS  PubMed  Google Scholar 

  18. Wu SG, Shih JY. Management of acquired resistance to EGFR TKI-targeted therapy in advanced non-small cell lung cancer. Mol Cancer. 2018;17(1):38.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Finlay MR, Anderton M, Ashton S, et al. Discovery of a potent and selective EGFR inhibitor (AZD9291) of both sensitizing and T790M resistance mutations that spares the wild type form of the receptor. J Med Chem. 2014;57(20):8249–67.

    Article  CAS  PubMed  Google Scholar 

  20. Remon J, Steuer CE, Ramalingam SS, et al. Osimertinib and other third-generation EGFR TKI in EGFR-mutant NSCLC patients. Ann Oncol. 2018;29(Suppl 1):i20–7.

    Article  CAS  PubMed  Google Scholar 

  21. Cross DA, Ashton SE, Ghiorghiu S, et al. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 2014;4(9):1046–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Jiangsu Hansoh Pharmaceutical Group. Hansoh Pharma's Ameile (almonertinib) receives marketing authorization in China for second-line treatment for patients with EGFR T790M-mutation non-small cell lung cancer [media release]. 2020. http://www.hspharm.com. Accessed 06 Dec 2021.

  23. Jiangsu Hansoh Pharmaceutical Group. Aumolertinib mesylate: Chinese product manual. Lianyungang City: Jiangsu Hansoh Pharmaceutical Group. 2021.

  24. Deeks ED. Furmonertinib: first approval. Drugs. 2021;81(15):1775–80.

    Article  CAS  PubMed  Google Scholar 

  25. Dhillon S. Lazertinib: first approval. Drugs. 2021;81(9):1107–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Hansoh Pharmaceutical Group Company Limited. Drug registration approval of Ameile in first line locally advanced or metastatic EGFR-mutated non-small cell lung cancer [media release]. http://www.hspharm.com/upload/file/2021/12/16/a1de0a25b5c3413a8fd3ca1ee81d2cc7.pdf. Accessed 16 Dec 2021.

  27. Yang JC, Camidge DR, Yang CT, et al. Safety, efficacy, and pharmacokinetics of almonertinib (HS-10296) in pretreated patients with EGFR-mutated advanced NSCLC: a multicenter, open-label, phase 1 trial. J Thorac Oncol. 2020;15(12):1907–18.

    Article  CAS  PubMed  Google Scholar 

  28. Gao P., Zhang F., Tong Z., et al. Discovery of a third generation EGFR inhibitor which is highly selective and potent against both resistant and activating EGFR mutations for NSCLC therapy [abstract no. 3063]. In: 2016 AACR meeting. 2016.

  29. Lu S, Wang Q, Zhang G, et al. Efficacy of aumolertinib (HS-10296) in patients with advanced EGFR T790M+ NSCLC: updated post-National Medical Products Administration approval results from the APOLLO registrational trial. J Thorac Oncol. 2021. https://doi.org/10.1016/j.jtho.2021.10.024.

    Article  PubMed  Google Scholar 

  30. Lu S, Wang Q, Zhang G et al. Final results of APOLLO study: overall survival (OS) of aumolertinib in patients with pretreated EGFR T790M positive locally advanced or metastatic non small cell lung cancer (NSCLC) [abstract no. 1208P plus poster]. Ann Oncol. 2021;32(Suppl 5):S962.

  31. Zhang Y, Zhang Y, Niu W, et al. Experimental study of almonertinib crossing the blood-brain barrier in EGFR-mutant NSCLC brain metastasis and spinal cord metastasis models. Front Pharmacol. 2021;12:750031.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Lu S, Dong X, Jian H, et al. Randomized phase III trial of aumolertinib (HS-10296, Au) versus gefitinib (G) as first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) and EGFR exon 19 del or L858R mutations (EGFRm) [abstract no. 9013 plus poster]. J Clin Oncol. 2021;39(15 Suppl):463s.

    Google Scholar 

  33. Tan CS, Kumarakulasinghe NB, Huang YQ, et al. Third generation EGFR TKIs: current data and future directions. Mol Cancer. 2018;17(1):29.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Lamb YN. Osimertinib: a review in previously untreated, EGFR mutation-positive, advanced NSCLC. Target Oncol. 2021;16(5):687–95.

    Article  PubMed  PubMed Central  Google Scholar 

  35. National Comprehensive Cancer Network®. Clinical practice guidelines in oncology (NCCN Guidelines®): non-small cell lung cancer (version 1.2022). 2022. http://www.nccn.org/. Accessed 14 Feb 2022.

  36. Hanna NH, Robinson AG, Temin S, et al. Therapy for stage IV non-small-cell lung cancer with driver alterations: ASCO and OH (CCO) joint guideline update. J Clin Oncol. 2021;39(9):1040–91.

    Article  CAS  PubMed  Google Scholar 

  37. Planchard D, Popat S, Kerr K, et al. Metastatic non-small cell lung cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018;29(Suppl 4):192–237.

    Article  Google Scholar 

  38. Wang H. A dose exploration study of almonertinib for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients with newly diagnosed or recurrent brain/leptomeningeal metastasis (ARTISTRY) [abstract no. 1369TiP]. Ann Oncol. 2021;32(Suppl 5):S949-1039.

    Google Scholar 

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Acknowledgments

During the peer review process, the manufacturer of aumolertinib was offered the opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

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    Matt Shirley & Susan J. Keam

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  1. Matt Shirley
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Correspondence to Matt Shirley.

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The preparation of this review was not supported by any external funding.

Authorship and conflicts of interest

M. Shirley and S. Keam are salaried employees of Adis International Ltd/Springer Nature, and declare no relevant conflicts of interest. All authors contributed to the review and are responsible for the article content.

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Additional information

The manuscript was reviewed by: C.-C. Lin, National Taiwan University Hospital, Taipei, Taiwan; H. Hayashi, Kindai University Faculty of Medicine, Medical Oncology, Osaka, Japan; R. Rosell, Catalan Institute of Oncology, Institute for Health Science Research Germans Trias i Pujol (IGTP), Barcelona, Spain.

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Shirley, M., Keam, S.J. Aumolertinib: A Review in Non-Small Cell Lung Cancer. Drugs 82, 577–584 (2022). https://doi.org/10.1007/s40265-022-01695-2

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