AENEAS: A Randomized Phase III Trial of Aumolertinib Versus Gefitinib as First-Line Therapy for Locally Advanced or MetastaticNon–Small-Cell Lung Cancer With EGFR Exon 19 Deletion or L858R Mutations

Abstract

PURPOSE Aumolertinib (formerly almonertinib; HS-10296) is a novel third-generation epidermal growth factor receptor tyrosine kinase inhibitor approved in China. This double-blind phase III trial evaluated the efficacy and safety of aumolertinib compared with gefitinib as a first-line treatment for locally advanced or metastatic EGFR-mutated non–small-cell lung cancer (NSCLC; ClinicalTrials.gov identifier: NCT03849768 ). METHODS Patients at 53 sites in China were randomly assigned 1:1 to receive either aumolertinib (110 mg) or gefitinib (250 mg) once daily. The primary end point was progression-free survival (PFS) per investigator assessment. RESULTS A total of 429 patients who were naïve to treatment for locally advanced or metastatic NSCLC were enrolled. PFS was significantly longer with aumolertinib compared with gefitinib (hazard ratio, 0.46; 95% CI, 0.36 to 0.60; P < .0001). The median PFS with aumolertinib was 19.3 months (95% CI, 17.8 to 20.8) versus 9.9 months with gefitinib (95% CI, 8.3 to 12.6). Objective response rate and disease control rate were similar in the aumolertinib and gefitinib groups (objective response rate, 73.8% and 72.1%, respectively; disease control rate, 93.0% and 96.7%, respectively). The median duration of response was 18.1 months (95% CI, 15.2 to not applicable) with aumolertinib versus 8.3 months (95% CI, 6.9 to 11.1) with gefitinib. Adverse events of grade ≥ 3 severity (any cause) were observed in 36.4% and 35.8% of patients in the aumolertinib and gefitinib groups, respectively. Rash and diarrhea (any grade) were observed in 23.4% and 16.4% of patients who received aumolertinib compared with 41.4% and 35.8% of those who received gefitinib, respectively. CONCLUSION Aumolertinib is a well-tolerated third-generation epidermal growth factor receptor tyrosine kinase inhibitor that could serve as a treatment option for EGFR-mutant NSCLC in the first-line setting.

Blockade of STAT3/IL-4 overcomes EGFR T790M-cis-L792F-induced resistance to osimertinib via suppressing M2 macrophages polarization

“…twice a week, MedChem Express). Tumor volumes were calculated using the formula length × width 2 × 0.52. Mice were sacrificed by CO 2 without suffering, and the tumors were dissected.…”

“…Tyrosine kinase inhibitors (TKIs) targeting mutant EGFR have brought great survival benefits to patients. With the progresses of drug development, third-generation TKIs, including osimertinib, aumolertinib and furmonertinib, have been recommended as the first-line setting for EGFR mutant NSCLC patients, 1 , 2 , 3 as salvage treatment for T790M mutation-positive patients after resistance to first- and second-generation EGFR TKIs 4 , 5 , 6 , 7 and as adjuvant therapy for post-surgery EGFR-mutant NSCLCs. 8 Other developing third-generation TKIs, including lazertinib, 9 abivertinib, 10 and rezivertinib 11 have shown powerful anti-tumor potentials in T790M-positive NSCLC patients.…”

Central Nervous System Efficacy of Furmonertinib (AST2818) Versus Gefitinib as First-Line Treatment for EGFR-Mutated NSCLC: Results From the FURLONG Study

“…EGFR-sensitizing mutations are the most detected driven mutation in NSCLC, which can be as high as 46.3% in Asian patients with advanced stage adenocarcinoma, 2 and EGFR tyrosine kinase inhibitors (TKIs) are the standard first-line treatment on the basis of the results of well-designed randomized controlled trials. [3][4][5][6][7][8][9][10] Third-generation EGFR TKIs were primarily developed to overcome a secondary EGFR T790M mutation causing resistance post firstor secondgeneration EGFR TKI treatment and found to have superior efficacy compared with first-generation EGFR TKIs in first-line settings. [8][9][10] The frequency of brain metastases is reported to be 25% during the course of NSCLC and to be 48% to 50% in patients with EGFR-sensitizing mutations.…”

“…[3][4][5][6][7][8][9][10] Third-generation EGFR TKIs were primarily developed to overcome a secondary EGFR T790M mutation causing resistance post firstor secondgeneration EGFR TKI treatment and found to have superior efficacy compared with first-generation EGFR TKIs in first-line settings. [8][9][10] The frequency of brain metastases is reported to be 25% during the course of NSCLC and to be 48% to 50% in patients with EGFR-sensitizing mutations. 11 As EGFR TKIs are the first choice to treat EGFR-sensitizing mutated NSCLC, developing drugs with brain penetration is of high importance.…”

Aumolertinib in EGFR-Mutant Lung Cancer: Will the Promise of Cost Disruption Ease Access?

“…It was approved for second-line treatment in China for patients with emergent EGFR T790M-resistant mutations on the basis of the results of the APOLLO trial. 5 The AENEAS trial, published in the article 6 that accompanies this editorial, is a double-blind, randomized phase III trial comparing the efficacy of aumolertinib with gefitinib in patients with treatment-naive, metastatic EGFR -mutant non–small-cell lung cancer (exon 19 deletion and L858R). The trial met its primary end point of an improvement in PFS, with a near doubling of median PFS (19.3 v 9.9 months; hazard ratio 0.46; 95% CI, 0.36 to 0.60; P < .0001), and the benefit was seen across all prespecified stratification factors.…”