Kocaeli Med J. 2021; 10(2): 51-56 | DOI: 10.5505/ktd.2021.82856

Clinical Effects of T790M Mutation in EGFR Tyrosine Kinase Inhibitor Resistant NSCLC Patients

Filiz Güldaval¹, Ceyda Anar², Melih Büyükþirin¹, Merve Ayýk Türk¹, Günseli Balcý¹, Mine Gayaf¹, Murat Akyol⁵, Ýbrahim Onur Alýcý³, Gülru Polat¹, Gülistan Karadeniz¹, Aysu Ayrancý³, Fatma Demirci Üçsular¹, Kadri Murat Erdoðan⁴, Yaþar Kutbay⁴, Þener Arýkan⁴, Özgür Batum¹, Berna Kömürcuoðlu¹, Sinem Ermin^1
1Department of Chest Disease, University of Health Sciences Doctor Suat Seren Chest Diseases and Thoracic Surgery Education and Research Hospital, Izmir, Turkey
²Department of Chest Disease, Ýzmir Katip Celebi University Ataturk Education and Research Hospital, Izmir, Turkey
³Department of Chest Disease, Ýzmir Bakýrcay University Cigli Education and Research Hospital, Izmir, Turkey
⁴Department of Medical Genetics, Ýzmir Tepecik Education and Research Hospital, Izmir, Turkey
⁵Department of Medical Oncology, Ýzmir Bakýrcay University Cigli Education and Research Hospital, Izmir, Turkey

INTRODUCTION: To compare patient characteristics between the T790M-positive and T790M-negative 29.06.2021 populations, and to analyze the post-progression survival (PPS) after initial tyrosine kinase inhibitor (TKI) failure in order to investigate the prognosis in patients undergoing rebiopsy.
METHODS: We investigated the patient characteristics, including the initial EGFR-TKI response and T790M status at the time of rebiopsy or liquid biopsy, subsequent treatment after resistance to the initial EGFR-TKI (the presence of EGFR-TKI re-challenge), treatment just before biopsy and/or rebiopsy (EGFR-TKIs or chemotherapy), the timing of the rebiopsy (just after the initial EGFR-TKI failure or others).
RESULTS: No difference was found between the two groups with T790M mutation positive and negative in terms of age, gender, and metastasis location. Only patients with positive T790M mutation had higher progression after TKI use compared to negative ones (p: 0.000). The progression-free median survival in patients using TKI was 19.33 months in the group with T790M mutation and 22.25 months in the negative group. Overall survival was found to be 75 months and 27.5 months in the T790M positive and negative group, respectively, and this was statistically significant. (p: 0.009).
DISCUSSION AND CONCLUSION: Overall survival was significantly longer in the T790M positive group than in the T790M negative group. In addition, liquid biopsy can be performed several times for patients with progression after EGFR-TKI use and who do not want to undergo tissue biopsy.

Keywords: liquid býopsy, lung cancer, survival, T790M mutation, tissue biopsy

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EGFR Tirozin Kinaz Ýnhibitörlerine Dirençli KHDAK Hastalarýnda T790M Mutasyonunun Klinik Etkileri

Filiz Güldaval¹, Ceyda Anar², Melih Büyükþirin¹, Merve Ayýk Türk¹, Günseli Balcý¹, Mine Gayaf¹, Murat Akyol⁵, Ýbrahim Onur Alýcý³, Gülru Polat¹, Gülistan Karadeniz¹, Aysu Ayrancý³, Fatma Demirci Üçsular¹, Kadri Murat Erdoðan⁴, Yaþar Kutbay⁴, Þener Arýkan⁴, Özgür Batum¹, Berna Kömürcuoðlu¹, Sinem Ermin^1
1Saðlýk Bilimleri Üniversitesi Doktor Suat Seren Göðüs Hastalýklarý ve Cerrahisi Eðitim Araþtýrma Hastanesi, Göðüs Hastalýklarý Ana Bilim Dalý, Ýzmir, Türkiye
²Ýzmir Katip Çelebi Üniversitesi Atatürk Eðitim ve Araþtýrma Hastanesi, Göðüs Hastalýklarý Ana Bilim Dalý, Ýzmir, Türkiye
³Ýzmir Bakýrçay Üniversitesi Çiðli Eðitim Araþtýrma Hastanesi, Göðüs Hastalýklarý Ana Bilim Dalý, Ýzmir, Turkiye
⁴Ýzmir Tepecik Eðitim ve Araþtýrme Hastanesi, Týbbi Onkoloji Ana Bilim Dalý, Ýzmir, Turkiye
⁵Ýzmir Bakýrçay Üniversitesi Çiðli Eðitim Araþtýrma Hastanesi, Medikal Onkoloji Ana Bilim Dalý, Ýzmir, Turkiye

GÝRÝÞ ve AMAÇ: T790M - pozitif ve T790M - negatif popülasyonlar arasýndaki hasta özellikleri karþýlaþtýrýldý ve ilk tirozin kinaz inhibitörü (TKI) baþarýsýzlýðýndan sonra progresyon sonrasý saðkalým (PPS) analiz edilerek yeniden biyopsi yapýlan hastalarda prognoz araþtýrýldý.
YÖNTEM ve GEREÇLER: Hastalarýn karakteristik özellikleri, EGFR-TKI yanýtý, rebiyopsi veya likit biyopsi sýrasýndaki EGFR durumu, rebiyopsi öncesi uygulanan tedavi (kemoterapi/ EGFR-TKI), ilk EGFR-TKI’a direnç geliþtikten sonraki tedavi ve biyopsi zamaný (ilk EGFR-TKI baþarýsýzlýðý sonrasý) araþtýrýlmýþtýr.
BULGULAR: T790M mutasyonu pozitif ve negatif olan iki grup arasýnda yaþ, cinsiyet ve metastaz yeri arasýnda fark saptanmadý. Yalnýzca T790M mutasyonu pozitif olan hastalarda TKÝ kullanýmý sonrasý progresyonun negatif olanlara göre daha fazla olduðu görüldü (p: 0.001). TKÝ kullanan hastalarda progresyonsuz median saðkalým T790M mutasyonu olan grupta 19,33 ay iken negative olan grupta 22.25 ay olarak saptandý. Genel saðkalým T790M pozitif ve negative olan grupta sýrasýyla 75 ay ve 27,5 ay olarak bulundu ve bu istatistiksel olarak anlamlý idi (p: 0.009).
TARTIÞMA ve SONUÇ: Genel saðkalým T790M pozitif grupta,T790M negatif gruba göre istatistiksel olarak anlamlý düzeyde uzun olarak saptandý. Ayrýca EGFR-TKI kullanýmý sonrasý progresyon olan ve doku biyopsisi yaptýrmak istemeyen hastalara likit biyopsisinin birkaç kez yapýlabilir.

Anahtar Kelimeler: akciðer kanseri, doku biyopsi, likit biyopsi, saðkalým, T790M mutasyonu

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