Histologic Transformation in an EGFR-Mutant Lung Cancer in a Filipino Patient treated with Afatinib

A Case Report and Review of Literature

Authors

  • Steffanie Charlyne Tamayo St. Luke's Medical Center, Quezon City, Philippines
  • Joanmarie Balolong-Garcia St. Luke's Medical Center, Quezon City, Philippines
  • Michelle Joanne Alcantara St. Luke's Medical Center, Quezon City, Philippines
  • Rubi Li St. Luke's Medical Center, Quezon City, Philippines
  • Daphne Ang St. Luke's Medical Center, Quezon City, Philippines
  • Jose Jasper Andal St. Luke's Medical Center, Quezon City, Philippines
  • Rex Michael Santiago St. Luke's Medical Center, Quezon City, Philippines

DOI:

https://doi.org/10.21141/PJP.2019.15

Keywords:

Lung cancer, adenocarcinoma, small cell carcinoma, receptor, epidermal growth factor, cell transformation, neoplastic

Abstract

We report a case of a 64-year-old Filipino male who initially presented with chronic cough, easy fatigability, and weight loss. Work-ups lead to a diagnosis of lung adenocarcinoma with epidermal growth factor receptor (EGFR) exon 19 deletion. Patient was placed on targeted therapy with Afatinib. He was able to complete 17 months of targeted therapy with relatively stable disease before experiencing recurrence of easy fatigability. Work-ups then lead to a diagnosis of a high-grade neuroendocrine tumor consistent with small cell lung carcinoma (SCLC). Afatinib was then discontinued and the patient was started on Carboplatin and Etoposide. However, after only one cycle, the patient’s symptoms progressed and the patient eventually expired. Histological transformation of EGFR-mutant adenocarcinoma to SCLC as a mechanism of resistance to targeted therapy has been documented in literature since 2006. However, to our knowledge, this is the first fully-documented case of histologic transformation occurring in a Filipino patient. As molecular targeted therapy and immunotherapy become standard-of-care in our country, it is of paramount importance that clinicians and pathologists are aware of the various mechanisms of resistance that can occur as a result of these treatments.

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Author Biographies

Steffanie Charlyne Tamayo, St. Luke's Medical Center, Quezon City, Philippines

Resident, Institute of Pathology,

Joanmarie Balolong-Garcia, St. Luke's Medical Center, Quezon City, Philippines

Fellow, Department of Medical Oncology

Michelle Joanne Alcantara, St. Luke's Medical Center, Quezon City, Philippines

Fellow, Department of Medical Oncology

Rubi Li, St. Luke's Medical Center, Quezon City, Philippines

Consultant, Department of Medical Oncology

Daphne Ang, St. Luke's Medical Center, Quezon City, Philippines

Consultant [Molecular Pathology], Institute of Pathology

Jose Jasper Andal, St. Luke's Medical Center, Quezon City, Philippines

Consultant [Molecular Pathology], Institute of Pathology

Rex Michael Santiago, St. Luke's Medical Center, Quezon City, Philippines

Consultant [Lung and Thoracic Pathology] Institute of Pathology

References

1. Adelstein DJ, Tomashefski JF Jr, Snow NJ, Horrigan TP, Hines JD. Mixed small cell and non-small cell lung cancer. Chest. 1986;89(5):699-704. https://pubmed.ncbi.nlm.nih.gov/3009096. https://doi.org/10.1378/chest.89.5.699.

2. Mangum MD, Greco FA, Hainsworth JD, Hande KR, Johnson, DH. Combined small-cell and non-small-cell lung cancer. J Clin Oncol. 1989;7(5):607-12. https://pubmed.ncbi.nlm.nih.gov/2540288. https://doi.org/10.1200/JCO.1989.7.5.607.

3. Wallace AS, Arya M, Frazier SR, Westgate S, Wang Z, Doll D. Combined small-cell lung carcinoma: an institutional experience. Thorac Cancer. 2014;5(1): 57-62. https://pubmed.ncbi.nlm.nih.gov/26766973. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4704284. https://doi.org/10.1111/1759-7714.12059.

4. Oser MG, Niederst MJ, Sequist LV, Engelman JA. Transformation from non-small cell lung cancer to small cell lung cancer: molecular drivers and cells of origin. Lancet Oncol. 2015;16(4): e165-72. https://pubmed.ncbi.nlm.nih.gov/25846096. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4470698. https://doi.org/10.1016/S1470-2045(14)71180-5.

5. Suda K, Murakami I, Sakai K, et al. Small cell lung cancer transformation and T790M mutation: complimentary roles in acquired resistance to kinase inhibitors in lung cancer. Scientific Reports 5. 2015; Article number 14447. https://www.nature.com/articles/srep14447. Accessed 24 April 2019.

6. Chai CS, Liam CK, Pang YK. Case series of small cell lung cancer transformation post tyrosine kinase inhibitor failure. Ann Oncol. 2017;28(suppl 10):x153-4. https://oncologypro.esmo.org/Meeting-Resources/ESMO-Asia-2017-Congress/Case-Series-of-Small-Cell-Lung-Cancer-Transformation-Post-Tyrosine-Kinase-Inhibitor-Failure-498P. Accessed 30 April 2019.

7. Morgillo F, Della Corte CM, Fasano M, Ciardiello F. Mechanisms of resistance to EGFR-targeted drugs: lung cancer. ESMO Open. 2016; 1(3):e000060. https://pubmed.ncbi.nlm.nih.gov/27843613 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070275. https://doi.org/10.1136/esmoopen-2016-000060.

8. Marcoux N, Gettinger SN, O’Kane G, et al. EGFR-mutant adenocarcinomas that transform to small-cell lung cancer and other neuroendocrine carcinomas: clinical outcomes. Journal of Clinical Oncology. 2019;37(4):278-85. https://pubmed.ncbi.nlm.nih.gov/30550363. https://doi.org/10.1200/JCO.18.01585.

9. Zakowski MF, Ladanyi M, Kris, MG. EGFR mutations in small-cell lung cancers in patients who have never smoked. N Engl J Med. 2006;355(2):213–5. https://pubmed.ncbi.nlm.nih.gov/16837691. https://doi.org/10.1056/NEJMc053610.

10. Fallet, V, Ruppert, A, Poulot, V, et al. Secondary resistance to erlotinib: acquired T790M mutation and small-cell lung cancer transformation in the same patient. J Thoracic Oncol. 2012;7(6): 1061-3. https://pubmed.ncbi.nlm.nih.gov/22588159. https://doi.org/10.1097/JTO.0b013e31824fea45.

11. Kuiper JL, Heideman DA, Thunnissen E, et al. Incidence of T790M mutation in (sequential) rebiopsies in EGFR-mutated NSCLC-patients. Lung Cancer. 2014;85(1): 19-24. https://pubmed.ncbi.nlm.nih.gov/24768581. https://doi.org/10.1016/j.lungcan.2014.03.016.

12. Lin Q, Cai G, Yang K, Yang L, Chen C, Li, Y. Case report: small cell transformation and metastasis to the breast in a patient with lung adenocarcinoma following maintenance treatment with epidermal growth factor receptor tyrosine kinase inhibitors. BMC Cancer. 2016;16:593. https://pubmed.ncbi.nlm.nih.gov/27488410. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972970. https://doi.org/ 10.1186/s12885-016-2623-4.

13. Varghese, AM, Zakowski, MF, Yu, HA, et al. Small-cell lung cancers in patients who never smoked cigarettes. J Thorac Oncology. 2014; 9(6):892-6. https://pubmed.ncbi.nlm.nih.gov/24828667. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4199745. https://doi.org/10.1097/JTO.0000000000000142.

14. Watanabe S, Sone T, Matsui T, et al. Transformation to small-cell lung cancer following treatment with EGFR tyrosine kinase inhibitors in a patient with lung adenocarcinoma. Lung Cancer. 2013; 82(2): 370-2. https://doi.org/10.1016/j.lungcan.2013.06.003.

15. Zhang, B, Xu, J, Wang, S, et al. Characteristics and outcome of small cell lung cancer patients (SCLC) transformed from adenocarcinoma after tyrosine kinase inhibitors treatment. Annals of Oncology. 2018; 29 (Suppl 9): ix150-60. https://oncologypro.esmo.org/Meeting-Resources/ESMO-Asia-2018-Congress/Characteristics-and-outcome-of-small-cell-lung-cancer-patients-SCLC-transformed-from-adenocarcinoma-after-tyrosine-kinase-inhibitors-treatment. Accessed 30 April 2019.

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Published

2019-09-15

How to Cite

Tamayo, S. C., Balolong-Garcia, J., Alcantara, M. J., Li, R., Ang, D., Andal, J. J., & Santiago, R. M. (2019). Histologic Transformation in an EGFR-Mutant Lung Cancer in a Filipino Patient treated with Afatinib: A Case Report and Review of Literature. PJP, 4(2), 43–47. https://doi.org/10.21141/PJP.2019.15

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