An epidermal growth factor receptor compound mutation of L858R with S768I in advanced non-small-cell lung cancer: a case report.

EGFR mutation Afatinib Case report L858R S768I

Journal

Journal of medical case reports
ISSN: 1752-1947
Titre abrégé: J Med Case Rep
Pays: England
ID NLM: 101293382

Informations de publication

Date de publication:
18 Mar 2024
Historique:
received: 11 12 2023
accepted: 30 01 2024
medline: 18 3 2024
pubmed: 18 3 2024
entrez: 18 3 2024
Statut: epublish

Résumé

In the current treatment landscape for non-small cell lung cancers, epidermal growth factor receptor-tyrosine kinase inhibitors have emerged as a well-established treatment option for patients with advanced or metastatic disease. This is particularly true for those with commonly occurring epidermal growth factor receptor mutations. However, the therapeutic efficacy of these agents for so-called rare epidermal growth factor receptor mutations, and in particular those characterized by a high degree of complexity, such as double mutations, remains a subject of clinical uncertainty. In this context, we present the case of a 64-year-old man of Moroccan descent, a lifelong non-smoker, diagnosed with metastatic non-small cell lung cancer characterized by a complex epidermal growth factor receptor mutation encompassing L858R and S768I. The patient subsequently underwent afatinib-based treatment, showing notable clinical results. These included a remarkable overall survival of 51 months, with a median progression-free survival of more than 39 months. This case report is a compelling testimony to the evolving therapeutic landscape of non-small cell lung cancers, providing valuable insight into the potential therapeutic efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors in the realm of rare and complex epidermal growth factor receptor mutations.

Sections du résumé

BACKGROUND BACKGROUND
In the current treatment landscape for non-small cell lung cancers, epidermal growth factor receptor-tyrosine kinase inhibitors have emerged as a well-established treatment option for patients with advanced or metastatic disease. This is particularly true for those with commonly occurring epidermal growth factor receptor mutations. However, the therapeutic efficacy of these agents for so-called rare epidermal growth factor receptor mutations, and in particular those characterized by a high degree of complexity, such as double mutations, remains a subject of clinical uncertainty.
CASE PRESENTATION METHODS
In this context, we present the case of a 64-year-old man of Moroccan descent, a lifelong non-smoker, diagnosed with metastatic non-small cell lung cancer characterized by a complex epidermal growth factor receptor mutation encompassing L858R and S768I. The patient subsequently underwent afatinib-based treatment, showing notable clinical results. These included a remarkable overall survival of 51 months, with a median progression-free survival of more than 39 months.
CONCLUSIONS CONCLUSIONS
This case report is a compelling testimony to the evolving therapeutic landscape of non-small cell lung cancers, providing valuable insight into the potential therapeutic efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors in the realm of rare and complex epidermal growth factor receptor mutations.

Identifiants

pubmed: 38494473
doi: 10.1186/s13256-024-04422-5
pii: 10.1186/s13256-024-04422-5
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

118

Informations de copyright

© 2024. The Author(s).

Références

D’Addario G, Früh M, Reck M, Baumann P, Klepetko W, Felip E. Metastatic non-small-cell lung cancer: ESMO clinical practice guidelines for diagnosis, treatment, and followup. Ann Oncol. 2010;21(Suppl. 5):116–9. https://doi.org/10.1093/annonc/mdq189 .
doi: 10.1093/annonc/mdq189
Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006;355(24):2542–50. https://doi.org/10.1056/NEJMoa061884 .
doi: 10.1056/NEJMoa061884 pubmed: 17167137
Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004;350(21):2129-2139. doi:10.1056/NEJMOA040938
Witta SE, Jotte RM, Konduri K, et al. Randomized phase II trial of erlotinib with and without entinostat in patients with advanced non-small-cell lung cancer who progressed on prior chemotherapy. J Clin Oncol. 2012;30(18):2248–55. https://doi.org/10.1200/JCO.2011.38.9411 .
doi: 10.1200/JCO.2011.38.9411 pubmed: 22508830 pmcid: 4798782
Keam B, Kim DW, Park JH, et al. Rare and complex mutations of epidermal growth factor receptor, and efficacy of tyrosine kinase inhibitor in patients with non-small cell lung cancer. Int J Clin Oncol. 2014;19(4):594–600. https://doi.org/10.1007/S10147-013-0602-1 .
doi: 10.1007/S10147-013-0602-1 pubmed: 23912954
Kauffmann-Guerrero D, Huber RM, Reu S, et al. NSCLC patients harbouring rare or complex EGFR mutations are more often smokers and might not benefit from first-line tyrosine kinase inhibitor therapy. Respiration. 2018;95(3):169–76. https://doi.org/10.1159/000484175 .
doi: 10.1159/000484175 pubmed: 29190621
Tam IYS, Leung ELH, Tin VPC, et al. Double EGFR mutants containing rare EGFR mutant types show reduced in vitro response to gefitinib compared with common activating missense mutations. Mol Cancer Ther. 2009;8(8):2142–51. https://doi.org/10.1158/1535-7163.MCT-08-1219 .
doi: 10.1158/1535-7163.MCT-08-1219 pubmed: 19671738
Kobayashi S, Canepa HM, Bailey AS, et al. Compound EGFR mutations and response to EGFR tyrosine kinase inhibitors. J Thorac Oncol. 2013;8(1):118–22. https://doi.org/10.1097/JTO.0B013E3182781E35 .
doi: 10.1097/JTO.0B013E3182781E35
Young Kim E, Na Cho E, Surng Park H, et al. Compound EGFR mutation is frequently detected with co-mutations of actionable genes and associated with poor clinical outcome in lung adenocarcinoma. Cancer Biol Ther. 2016;17:237. https://doi.org/10.1080/15384047.2016.1139235 .
doi: 10.1080/15384047.2016.1139235
Hata A, Yoshioka H, Fujita S, et al. Complex mutations in the epidermal growth factor receptor gene in non-small cell lung cancer. J Thorac Oncol. 2010;5(10):1524–8. https://doi.org/10.1097/JTO.0B013E3181E8B3C5 .
doi: 10.1097/JTO.0B013E3181E8B3C5 pubmed: 20808254
Zhao W, Song A, Xu Y, et al. Rare mutation-dominant compound EGFR-positive NSCLC is associated with enriched kinase domain-resided variants of uncertain significance and poor clinical outcomes. BMC Med. 2023;21(1):1–16. https://doi.org/10.1186/S12916-023-02768-Z/FIGURES/5 .
doi: 10.1186/S12916-023-02768-Z/FIGURES/5
Kitadai R, Okuma Y. Treatment strategies for non-small cell lung cancer harboring common and uncommon EGFR mutations: drug sensitivity based on exon classification, and structure-function analysis. Cancers (Basel). 2022;14(10):2519. https://doi.org/10.3390/CANCERS14102519 .
doi: 10.3390/CANCERS14102519 pubmed: 35626123 pmcid: 9139782
Wu SG, Yu CJ, Yang JCH, Shih JY. The effectiveness of afatinib in patients with lung adenocarcinoma harboring complex epidermal growth factor receptor mutation. Ther Adv Med Oncol. 2020;12:1758835920946156. https://doi.org/10.1177/1758835920946156 .
doi: 10.1177/1758835920946156 pubmed: 32843903 pmcid: 7418472
Bethune G, Bethune D, Ridgway N, Xu Z. Epidermal growth factor receptor (EGFR) in lung cancer: an overview and update. J Thorac Dis. 2010;2(1):48. https://doi.org/10.3978/J.ISSN.2072-1439.2010.02.01.017 .
doi: 10.3978/J.ISSN.2072-1439.2010.02.01.017 pubmed: 22263017 pmcid: 3256436
Gupta R, Dastane AM, Forozan F, et al. Evaluation of EGFR abnormalities in patients with pulmonary adenocarcinoma: the need to test neoplasms with more than one method. Mod Pathol. 2009;22(1):128–33. https://doi.org/10.1038/modpathol.2008.182 .
doi: 10.1038/modpathol.2008.182 pubmed: 18997733
Yasuda H, Park E, Yun CH, et al. Structural, biochemical, and clinical characterization of epidermal growth factor receptor (EGFR) exon 20 insertion mutations in lung cancer. Sci Transl Med. 2013;5:216. https://doi.org/10.1126/SCITRANSLMED.3007205/SUPPL_FILE/5-216RA177_SM.PDF .
doi: 10.1126/SCITRANSLMED.3007205/SUPPL_FILE/5-216RA177_SM.PDF
Leventakos K, Kipp BR, Rumilla KM, Winters JL, Yi ES, Mansfield AS. Brief report: S768I mutation in EGFR in patients with lungcancer. J Thorac Oncol. 2016;11(10):1798. https://doi.org/10.1016/J.JTHO.2016.05.007 .
doi: 10.1016/J.JTHO.2016.05.007 pubmed: 27211795 pmcid: 5035584
Yang JCH, Sequist LV, Geater SL, et al. 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. 2015;16(7):830–8. https://doi.org/10.1016/S1470-2045(15)00026-1 .
doi: 10.1016/S1470-2045(15)00026-1 pubmed: 26051236
Zhu X, Bai Q, Lu Y, et al. Response to tyrosine kinase inhibitors in lung adenocarcinoma with the rare epidermal growth factor receptor mutation S768I: a retrospective analysis and literature review. Target Oncol. 2017;12(1):81–8. https://doi.org/10.1007/s11523-016-0455-4 .
doi: 10.1007/s11523-016-0455-4 pubmed: 27538584
Kohsaka S, Petronczki M, Solca F, Maemondo M. Tumor clonality and resistance mechanisms in EGFR mutation-positive non-small-cell lung cancer: Implications for therapeutic sequencing. Futur Oncol. 2019;15(6):637–52. https://doi.org/10.2217/fon-2018-0736 .
doi: 10.2217/fon-2018-0736
Peng L, Song Z, Jiao S. Comparison of uncommon EGFR exon 21 L858R compound mutations with single mutation. Onco Targets Ther. 2015;8:905–10. https://doi.org/10.2147/OTT.S78984 .
doi: 10.2147/OTT.S78984 pubmed: 25960661 pmcid: 4410901
Li M, Zhou CZ, Yang JJ, et al. The in cis compound EGFR mutations in Chinese advanced non-small cell lung cancer patients. Cancer Biol Ther. 2019;20(8):1097–104. https://doi.org/10.1080/15384047.2019.1595280/SUPPL_FILE/KCBT_A_1595280_SM0961.PPTX .
doi: 10.1080/15384047.2019.1595280/SUPPL_FILE/KCBT_A_1595280_SM0961.PPTX pubmed: 30990107 pmcid: 6605978
Kobayashi S, Canepa HM, Bailey AS, et al. Compound EGFR mutations and response to EGFR tyrosine kinase inhibitors. J Thorac Oncol. 2013;8(1):118–22. https://doi.org/10.1097/JTO.0B013E3182781E35 .
doi: 10.1097/JTO.0B013E3182781E35
Kim EY, Cho EN, Park HS, et al. Compound EGFR mutation is frequently detected with co-mutations of actionable genes and associated with poor clinical outcome in lung adenocarcinoma. Cancer Biol Thera. 2016;17(3):237–45. https://doi.org/10.1080/15384047.2016.1139235 .
doi: 10.1080/15384047.2016.1139235
Xu H, Yang G, Liu R, et al. EGFR uncommon alterations in advanced non-small cell lung cancer and structural insights into sensitivity to diverse tyrosine kinase inhibitors. Front Pharmacol. 2022;13:3791. https://doi.org/10.3389/FPHAR.2022.976731/BIBTEX .
doi: 10.3389/FPHAR.2022.976731/BIBTEX
Chen K, Yu X, Wang H, et al. Uncommon mutation types of epidermal growth factor receptor and response to EGFR tyrosine kinase inhibitors in Chinese non-small cell lung cancer patients. Cancer Chemother Pharmacol. 2017;80(6):1179–87. https://doi.org/10.1007/S00280-017-3464-9 .
doi: 10.1007/S00280-017-3464-9 pubmed: 29063948
Cho JH, Lim SH, An HJ, et al. 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. 2020;38(5):488–95. https://doi.org/10.1200/JCO.19.00931 .
doi: 10.1200/JCO.19.00931 pubmed: 31825714
Masuda T, Sunaga N, Kasahara N, et al. Successful afatinib rechallenge in a patient with non-small cell lung cancer harboring EGFR G719C and S768I mutations. Thorac cancer. 2020;11(8):2351–6. https://doi.org/10.1111/1759-7714.13532 .
doi: 10.1111/1759-7714.13532 pubmed: 32529804 pmcid: 7396375
Huang CH, Ju JS, Chiu TH, et al. Afatinib treatment in a large real-world cohort of nonsmall cell lung cancer patients with common and uncommon epidermal growth factor receptor mutation. Int J cancer. 2022;150(4):626–35. https://doi.org/10.1002/IJC.33821 .
doi: 10.1002/IJC.33821 pubmed: 34558665
Eide IJZ, Stensgaard S, Helland Å, et al. Osimertinib in non-small cell lung cancer with uncommon EGFR-mutations: a post-hoc subgroup analysis with pooled data from two phase II clinical trials. Transl Lung Cancer Res. 2022;11(6):953–63. https://doi.org/10.21037/TLCR-21-995/COIF) .
doi: 10.21037/TLCR-21-995/COIF) pubmed: 35832438 pmcid: 9271433
Svaton M, Pesek M, Chudacek Z, Vosmiková H. Current two EGFR mutations in lung adenocarcinoma—case report. Klin Onkol. 2015;28(2):134–7. https://doi.org/10.14735/AMKO2015134 .
doi: 10.14735/AMKO2015134 pubmed: 25882025
Watanabe M, Oizumi S, Kiuchi S, et al. The effectiveness of afatinib in a patient with advanced lung adenocarcinoma harboring rare G719X and S768I mutations. Intern Med. 2018;57(7):993–6. https://doi.org/10.2169/INTERNALMEDICINE.9565-17 .
doi: 10.2169/INTERNALMEDICINE.9565-17 pubmed: 29225262
Yang Y, Zhang B, Li R, Liu B, Wang L. EGFR-tyrosine kinase inhibitor treatment in a patient with advanced non-small cell lung cancer and concurrent exon 19 and 21 EGFR mutations: a case report and review of the literature. Oncol Lett. 2016;11(5):3546–50. https://doi.org/10.3892/ol.2016.4409 .
doi: 10.3892/ol.2016.4409 pubmed: 27123149 pmcid: 4841118
Morimoto T, Yamasaki K, Shingu T, et al. A rare case of double primary lung adenocarcinomas with uncommon complex EGFR G719X and S768I mutations and pleomorphic carcinoma. Thorac Cancer. 2023;14(29):2981–4. https://doi.org/10.1111/1759-7714.15085 .
doi: 10.1111/1759-7714.15085 pubmed: 37614204 pmcid: 10569900
Simionato F, Calvetti L, Cosci M, Scarparo S, Aprile G. Case report: a metabolic complete response to upfront osimertinib in a smoker non-small cell lung cancer patient harbouring EGFR G719A/V769M complex mutation. Oncol Targets Ther. 2020;13:12027–31. https://doi.org/10.2147/OTT.S280933 .
doi: 10.2147/OTT.S280933
Falla-Martinez JC, Espinosa D, Baena JC, Rodriguez LX, Sua LF, Zambrano AR. An endothelial growth factor receptor compound mutation of T790M substitution with exon 19 deletion in a previously untreated patient: a case report. J Med Case Rep. 2019;13(1):1–8. https://doi.org/10.1186/S13256-019-2075-Y/TABLES/1 .
doi: 10.1186/S13256-019-2075-Y/TABLES/1
He S-Y, Lin Q-F, Chen J, Yu G-P, Zhang J-L, Shen D. Efficacy of afatinib in a patient with rare EGFR (G724S/R776H) mutations and amplification in lung adenocarcinoma: a case report. World J Clin cases. 2021;9(6):1329–35. https://doi.org/10.12998/wjcc.v9.i6.1329 .
doi: 10.12998/wjcc.v9.i6.1329 pubmed: 33644199 pmcid: 7896682
Qin BD, Jiao XD, Yuan LY, et al. 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. Oncol Targets Ther. 2018;11:4739–45. https://doi.org/10.2147/OTT.S167346 .
doi: 10.2147/OTT.S167346
Yang M, Tong X, Xu X, et al. 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. 2018;121:1–4. https://doi.org/10.1016/j.lungcan.2018.04.006 .
doi: 10.1016/j.lungcan.2018.04.006 pubmed: 29858019
Li L, Huang S, Qin L, Yan N, Shen S, Li X. Successful treatment of lung adenocarcinoma complicated with a rare compound EGFR mutation L833V/H835L using aumolertinib: a case report and literature review. Front Pharmacol. 2023;14:1257592. https://doi.org/10.3389/FPHAR.2023.1257592/BIBTEX .
doi: 10.3389/FPHAR.2023.1257592/BIBTEX pubmed: 37719840 pmcid: 10499621

Auteurs

Sara Boukansa (S)

Laboratory of Biomedical and Translational Research, Faculty of Medicine and Pharmacy, Sidi Mohamed Ben Abdellah University, Fez, Morocco. sara.boukansa@usmba.ac.ma.
Laboratory of Anatomic Pathology and Molecular Pathology, University Hospital Hassan II, Sidi Mohamed Ben Abdellah University, Fez, Morocco. sara.boukansa@usmba.ac.ma.

Ismail Mouhrach (I)

Unit of Medical Genetics and Oncogenetics, University Hospital Hassan II, Sidi Mohamed Ben Abdellah University, Fez, Morocco.

Fatima El Agy (F)

Laboratory of Biomedical and Translational Research, Faculty of Medicine and Pharmacy, Sidi Mohamed Ben Abdellah University, Fez, Morocco.
Laboratory of Anatomic Pathology and Molecular Pathology, University Hospital Hassan II, Sidi Mohamed Ben Abdellah University, Fez, Morocco.

Laila Bouguenouch (L)

Unit of Medical Genetics and Oncogenetics, University Hospital Hassan II, Sidi Mohamed Ben Abdellah University, Fez, Morocco.

Mounia Serraj (M)

Department of Pneumology, University Hospital Hassan II, Sidi Mohamed Ben Abdellah University, Fez, Morocco.

Bouchra Amara (B)

Department of Pneumology, University Hospital Hassan II, Sidi Mohamed Ben Abdellah University, Fez, Morocco.

Yassine Ouadnouni (Y)

Department of Thoracic Surgery, University Hospital Hassan II, Sidi Mohamed Ben Abdellah University, Fez, Morocco.

Mohamed Smahi (M)

Department of Thoracic Surgery, University Hospital Hassan II, Sidi Mohamed Ben Abdellah University, Fez, Morocco.

Badreeddine Alami (B)

Department of Radiology, University Hospital Hassan II, Sidi Mohamed Ben Abdellah University, Fez, Morocco.

Nawfel Mellas (N)

Department of Oncology, University Hospital Hassan II, Sidi Mohamed Ben Abdellah University, Fez, Morocco.

Zineb Benbrahim (Z)

Department of Oncology, University Hospital Hassan II, Sidi Mohamed Ben Abdellah University, Fez, Morocco.

Hinde El Fatemi (H)

Laboratory of Biomedical and Translational Research, Faculty of Medicine and Pharmacy, Sidi Mohamed Ben Abdellah University, Fez, Morocco.
Laboratory of Anatomic Pathology and Molecular Pathology, University Hospital Hassan II, Sidi Mohamed Ben Abdellah University, Fez, Morocco.

Classifications MeSH