EP1.14-11 Real-Life Data of Osimertinib in Pretreated Patients with Advanced Non-Small Cell Lung Cancer Harboring EGFR T790M Mutation

Abstract

Several clinical trials have demonstrated the efficacy and safety of osimertinib in pretreated patients with advanced non-small cell lung cancer (NSCLC) harbouring EGFR T790M resistance mutation. However, clinical real-world data on patient characteristics and efficacy of the drug is limited. We reviewed the medical records of T790M mutation-positive lung cancer patients treated with osimertinib between May 2016 and February 2019 in our institution. We calculated progression-free survival (PFS) and overall survival (OS) from osimertinib initiation. The study included 22 patients with a mean age of 59.6 years. 59% (13/22) were female and 100% had adenocarcinoma histology. We had an unusual high frequency of tobacco use in our series as 40.9% (9/22) of our patients were smokers (3/22) o former-smokers (6/22), with a mean of 35 pack-year (sd, 28.5). 45.5% (10/22) had exon 21 L858R mutations, whereas 54.5% (12/22) harboured exon 19 deletions (19del). One patient simultaneously had an exón 19 deletion and exon 20 S768I mutation. Osimertinib was used in second, third and fourth line in 50% (11/22), 27% (6/22) and 23% (5/22) of patients, respectively. All patients had liquid biopsy blood samples obtained prior to the start of the treatment, and T790M mutation could be detected in 86.4% (19/22), with a mean mutant-allele fraction of 4,11% (standard deviation 8.65, min 0, max 37.7). T790M was detected only in tissue in 2 patients and exclusively in cerebrospinal fluid in 1 of them. At the time of starting osimertinib, patients had a median of 3 metastatic sites (min 1, max 6), being the most frequent locations the lung (73%), the bone (64%), the pleura (59%), the central nervous system (23%) and the peritoneum (14%). Median follow-up duration was 10 months (IQR, 4.7-22.67). To the date, 63% (14/22) have experienced progression of the disease. Median PFS in our series was 8.9 (95% CI, 4.9-17.9 ) months, whereas median OS since osimertinib initiation was 18.2 (95% CI, 8.8-NE) months. Regarding to toxicity, 12 patients referred adverse events, 82.6% of which were mild (G1), being the most frequent toxicities neutropenia (9%), diarrhoea (9%), hypertransaminasemia (9%) and asthenia (9%). Only 1 G3 event was recorded (asymptomatic hyperamilasemia). The efficacy of osimertinib in real-world practice was similar the observed in clinical trials, with a favourable adverse effect profile. Liquid biopsy is an effective non-invasive method to assess the presence of the T790M resistance mutation prior to the start of osimertinib.