Dynamics of disease progression during treatment with Osimertinib in patients with EGFR T790M‐positive non‐small cell lung cancer

Abstract

Background: Patterns of treatment failure and subsequent treatment in nonsmall cell lung cancer (NSCLC) patients treated with osimertinib are scarcely known. We analyzed the disease progression during osimertinib treatment to identify potential treatment strategies. Methods:We identified advanced NSCLC patients who commenced osimertinib treatment after progression on previous epidermal growth factor receptor (EGFR)-tyrosine-kinase inhibitor (TKI) from June 2014 to November 2018 from electronic records. Patients' tumor characteristics, efficacy outcomes, affected organs from radiology studies, and treatment modalities before and after osimertinib were analyzed.Results: Eighty-four patients were included. At osimertinib initiation, bone (50.0%) and brain (41.9%) were the commonest single metastatic sites, whereas thoracic involvement (73.3%) was more frequent than bone (27.4%) or brain (20.2%) metastasis during disease progression on osimertinib. Oligo-progressive disease (PD) and central nervous system (CNS)-sanctuary PD were observed in 15 (17.9%) and 3 (3.6%) patients, respectively. Most patients without brain metastasis (BM) at osimertinib initiation remained BM-free (46/49, 93.9%), and 60% of patients (21/35) with pre-existing BM showed intracranial disease control despite extracranial PD. The resistance mechanisms to osimertinib were explored in 23 patients (27.4%), and T790M-loss was observed in 14 patients (60.9%) who had worse survival outcomes than those without T790M-loss (progression-free survival, 5.4 vs. 16.5 months, p = 0.02; overall survival, not reached, p = 0.03). Conclusion:PD during osimertinib treatment occurred preferentially in the thorax and pre-existing sites. Extracranial PD prevailed over intracranial PD regardless of baseline BM and prior brain radiation. These results support osimertinib's intracranial efficacy and may guide treatment strategies for EGFR-mutated NSCLC with BM.

The impact of EGFR T790M mutation status following the development of Osimertinib resistance on the efficacy of Osimertinib in non‐small cell lung cancer: A meta‐analysis

“…A total of 222 patients were selected from ten articles 13–15,26–32 . Of these 222 patients, 121 patients exhibited the loss of the T790M mutation subsequent to the emergence of resistance to Osimertinib (T790M‐loss group) and 101 patients maintained the T790M mutation (T790M‐maintenance group) while developing resistance to Osimertinib.…”

“…A total of 222 patients were selected from ten articles. 13 , 14 , 15 , 26 , 27 , 28 , 29 , 30 , 31 , 32 Of these 222 patients, 121 patients exhibited the loss of the T790M mutation subsequent to the emergence of resistance to Osimertinib (T790M‐loss group) and 101 patients maintained the T790M mutation (T790M‐maintenance group) while developing resistance to Osimertinib. Pooled analysis showed that the risk value for the T790M‐maintenance group was lower than for the T790M‐loss group (HR: 0.44, 95% CI: 0.30–0.66; Figure 2 ).…”

“…Three of the ten studies 14 , 27 , 32 provided OS data in addition to PFS data. The aggregated analysis reported a longer OS in the T790M‐maintenance group compared with the T790M‐loss group (HR: 0.3, 95% CI: 0.1–0.86; Figure 3 ) without heterogeneity ( I 2 = 0).…”

“…Because PFS and TTD are all cancer patient survival outcomes, a total of 478 patients selected from 14 studies 5 , 13 , 14 , 15 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 were included in the subgroup analyses of survival outcomes. Results showed that the T790M‐maintenance group had longer survival outcomes than the T790M‐loss group (HR: 0.58, 95% CI: 0.47–0.73; Figure 5 ).…”

“…To investigate the origins of heterogeneity, we conducted further subgroup analysis based on ethnicity to examine differences in the PFS in diverse populations. The study by some articles 13 , 14 , 15 , 27 , 28 , 29 , 30 , 31 , 32 was carried out in a predominantly Asian population, while Goldberg et al 26 focused on a non‐Asian population. Subgroup analysis revealed that the HR of the T790M‐maintenance group versus the T790M‐loss group was comparable in the Asian and non‐Asian populations (HR: 0.46, 95% CI: 0.31–0.68 for Asians; HR: 0.12, 95% CI: 0.01–1.27 for non‐Asians; Figure 7 ).…”