Safety and Efficacy of Epitinib for EGFR-Mutant Non-Small Cell Lung Cancer With Brain Metastases: Open-Label Multicentre Dose-Expansion Phase Ib Study.

Abstract

BACKGROUND:

Non-small-cell lung cancer (NSCLC) had poor prognosis in patients with brain metastasis. The trial evaluated the safety and efficacy of epitinib (HMPL-813), an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), for EGFR-mutant NSCLC with brain metastasis.

PATIENTS AND METHODS:

This open-label, dose-expansion phase Ib study (ClinicalTrials.gov: NCT02590952) was conducted at 7 Chinese centers and enrolled patients with EGFR-mutant advanced NSCLC with brain metastasis. Epitinib was administered at 120 mg or 160 mg, orally QD. The primary endpoint was safety and tolerability.

RESULTS:

Between April 2015 and April 2019, 72 patients were enrolled and received epitinib at 120 mg (n = 30) or 160 mg (n = 42). Treatment-related adverse events (TRAEs) of grade ≥3 occurred in 13 (43.3%) patients in 120 mg group and 21 (50.0%) in 160 mg group. The objective response rate (ORR) was 53.6% (95% CI 33.9%-72.5%) in 120 mg group and 40.5% (25.6%-56.7%) in 160 mg group. The median duration of response in the 120 mg and 160 mg groups were 7.40 months (95% CI 3.70-7.40) and 9.10 months (6.50-12.00), respectively. The median progression-free survival were 7.40 months (95% CI 5.40-9.20) and 7.40 months (5.50-10.00), respectively.

CONCLUSION:

In patients with EGFR-mutant NSCLC with brain metastasis, epitinib was well tolerable with a promising efficacy. According to the comprehensive assessment on safety and efficacy, 160 mg QD could be the recommended phase 2 dose.

• Authors: Qing Zhou, Mengzhao Wang, Helong Zhang, Qunying Hong, Xiaoqing Liu, Puhan Lu, Weiguo Su, Yi-Long Wu
• Journal: Clinical lung cancer (Clin Lung Cancer) Vol. 23 Issue 6 Pg. e353-e361 (09 2022) ISSN: 1938-0690 [Electronic] United States
• PMID: 35654732 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Elsevier Inc. All rights reserved.

Chemical References

• Protein Kinase Inhibitors
• EGFR protein, human
• ErbB Receptors

Topics

• Brain Neoplasms (drug therapy, genetics)
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics)
• ErbB Receptors (genetics)
• Humans
• Lung Neoplasms (chemically induced, drug therapy, genetics)
• Mutation (genetics)
• Protein Kinase Inhibitors