The real-life efficacy and safety of osimertinib in pretreated advanced non-small cell lung cancer patients with T790M mutation: a Turkish Oncology Group Study.

Mutlu Hızal ,Mustafa Gürbüz,Nail Paksoy,Ali Murat Tatlı,Alper Can,Burcu Caner,Ahmet Sezer,Ahmet Gülmez,Teoman Şakalar,Tuğba Başoğlu,Semra Paydaş,Şebnem Yücel,Perran Fulden Yumuk,Naziye Ak,Esra Zeynelgil,Adnan Aydıner,Yakup İriağaç,İvo Gökmen,Atike Gökçen Demiray,Ahmet Demirkazık,Aykut Demirkıran,Aykut Bahçeci,Cihan Erol,Bülent Yalçın,Deniz Can Güven,Murat Ayhan,Mehmet Ali Nahit Şendur,Yusuf Karakaş,Özgür Açıkgöz,Nil Molınas Mandel ,Abdallah Tm Shbair ,Ahmet Bılıcı ,Burak Bi̇lgi̇n

doi:10.1007/s00432-021-03748-7

Abstract

Osimertinib, an irreversible third-generation EGFR-TKI, is the standard of care for second-line treatment of T790M-mutant advanced NSCLC patients whose disease progressed after first-line EGFR-TKI therapy. In this multicenter study, we aimed to determine the real-life efficacy and safety of Osimertinib in pretreated advanced NSCLC patients with T790M mutation. This retrospective trial included advanced T790M-mutant pretreated NSCLC patients who received Osimertinib from 24 different centers in Turkey. Primary endpoint was time-to-treatment discontinuation (TTD). Secondary endpoints were objective response rate (ORR), overall survival (OS), and safety. Of 163 patients, 68.7% had EGFR exon 19 deletion and 22.7% had exon 21 L858R mutation. Osimertinib was given as second-line treatment in 96 patients (58.9%) and third-line in 48 patients (29.4%). After median of 13-month follow-up, median TTD was 21.6months with an 82.2% ORR. Estimated median OS was 32.1months. Grade 3-4 adverse events were seen in 11.7% of the patients. Osimertinib is a highly effective option in second- or third-line treatment of NSCLC patients with T790M mutation, with a favorable safety profile.

Highlights

Osimertinib, an irreversible third-generation Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), is the standard of care for second-line treatment of T790M-mutant advanced Non-small cell lung cancer (NSCLC) patients whose progressed after first-line EGFR-TKI therapy
Osimertinib was given as second-line treatment in 96 patients (58.9%) and third-line in 48 patients (29.4%)
First-generation EGFR tyrosine kinase inhibitors (TKIs) (Erlotinib, Gefitinib), and secondgeneration TKI, Afatinib were the standard of care options for first-line treatment of advanced NSCLC with EGFR exon 19 deletion and 21 mutations

Summary

Introduction

Osimertinib, an irreversible third-generation EGFR-TKI, is the standard of care for second-line treatment of T790M-mutant advanced NSCLC patients whose progressed after first-line EGFR-TKI therapy. T790M mutation occurs in exon 20 of the EGFR gene, converts ATP-binding pocket of the receptor to a nonpolar, hydrophobic state which interferes with drug-binding and causes a lack of efficacy [4]. This point mutation was demonstrated in 60% of the patients at the time of progression [5]

Methods

Results

Conclusion