Abivertinib in patients with T790M-positive advanced NSCLC and its subsequent treatment with osimertinib

Abstract

Background: Abivertinib is a novel oral, third generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that overcomes T790M-induced resistance in non-small cell lung cancer (NSCLC) patients. Here, we report the results of a complete and detailed clinical data of patients treated with abivertinib at our hospital in a phase I dose escalation/expansion study of abivertinib.

Methods: NSCLC patients with the EGFR T790M mutation were orally administered abivertinib (150-300 mg) twice daily for cycles of 28 continuous days and tumor response was assessed. Further data regarding subsequent treatment protocols and survival were collected.

Results: A total of 28 NSCLC patients were included. Of the 24 assessable patients, 12 (50%) achieved a partial response (PR), and six (25%) achieved stable disease (SD). Median progression-free survival (PFS) was 5.9 months (95% confidence interval (CI): 3.259-8.541) and median overall survival (OS) was 17.9 months (95% CI: 11.36-24.5). For salvage therapy in 15 (53.6%) patients after abivertinib, the median PFS following osimertinib treatment was 12 months. The median total treatment duration for the two third-generation EGFR TKIs was 15.9 months (95% CI: 12.5-19.3). The most frequent abivertinib-associated adverse effects were elevated hepatic transaminases (10/28, 35.7%) and diarrhea (10/28, 35.7%).

Conclusions: Abivertinib is a unique novel third-generation EGFR TKI with good tolerance and efficacy in EGFR T790M(+) NSCLC patients. For patients with progressive disease after treatment with abivertinib, osimertinib could be an option for subsequent therapy but further studies are required.

Key points: Abivertinib is a novel third-generation EGFR TKI targeting the EGFR T790M mutation Abivertinib is well tolerated and efficacious in T790M-positive patients Abivertinib has a unique structure, efficacy, and resistance mechanism compared with osimertinib Osimertinib treatment after AC0010 showed a good response.

Keywords: Abivertinib; T790M mutation; osimertinib; sequential treatment; third-generation EGFR TKI.