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.

Conflict of interest statement

Shun Lu

Consulting or Advisory Role: AstraZeneca, Pfizer, Boehringer Ingelheim, Hutchison MediPharma, Simcere Pharmaceutical Group, Zai Lab, GenomiCare, Yuhan, Prime Oncology, Roche

Speakers' Bureau: AstraZeneca, Roche, Hansoh Pharma, Hengrui Therapeutics

Research Funding: AstraZeneca (Inst), Hutchison MediPharma (Inst), BMS (Inst), Hengrui Therapeutics (Inst), BeiGene (Inst), Roche (Inst)

Xiaorong Dong

Consulting or Advisory Role: Hansoh Pharma

Research Funding: Hansoh Pharma (Inst)

Yuping Sun

Honoraria: Roche, Pfizer, AstraZeneca

Consulting or Advisory Role: AstraZeneca, Roche

Research Funding: Roche, Pfizer

Yinghua Ji

Research Funding: AoSaikang, CSPC Pharma, Hualan Bio (Inst)

Jianhua Shi

Honoraria: Roche, BeiGene

Consulting or Advisory Role: Hansoh Pharma

Research Funding: Hansoh Pharma (Inst)

Junguo Lu

Research Funding: Hansoh (Inst), Akesobio (Inst), Shanghai Henlius Biotech (Inst)

Shaoshui Chen

Consulting or Advisory Role: Hansoh Pharma

Research Funding: Hansoh Pharma (Inst)

Xinmin Yu

Research Funding: BeiGene, Innovent Biologics, BMS, MSD, Hansoh

Zhehai Wang

Consulting or Advisory Role: Hansoh Pharma

Research Funding: Hansoh Pharma (Inst)

Xingxiang Xu

Consulting or Advisory Role: Hansoh Pharma

Research Funding: Hansoh Pharma (Inst)

Jian Fang

Consulting or Advisory Role: Hansoh Pharma

Research Funding: Hansoh Pharma (Inst)

Yanping Hu

Consulting or Advisory Role: Hansoh Pharma

Research Funding: Hansoh Pharma (Inst)

Nong Yang

Consulting or Advisory Role: Hansoh Pharmaceutical Group Co, Ltd

Research Funding: Hansoh Pharmaceutical Group Co, Ltd

Xiangdong Zhou

Research Funding: MSD, AZ, Hansoh, Hengrui, Sanofi, J&J, BMS, BeiGene, Pfizer, GSK, Novartis, Chiesi (Inst)

You Lu

Honoraria: Roche/Genentech, AstraZeneca, Pfizer, Bristol Myers Squibb, Merck Sharp & Dohme, BeiGene

Consulting or Advisory Role: Roche/Genentech, AstraZeneca, Pfizer, Bristol Myers Squibb, Merck Sharp & Dohme, BeiGene

Qiming Wang

Consulting or Advisory Role: Hansoh Pharma

Research Funding: Hansoh Pharma (Inst)

Jianying Zhou

Consulting or Advisory Role: Hansoh Pharma

Research Funding: Hansoh Pharma (Inst)

Yuan Chen

Consulting or Advisory Role: Hansoh Pharma

Research Funding: Hansoh Pharma (Inst)

Haihua Yang

Consulting or Advisory Role: Hansoh Pharma

Research Funding: Hansoh Pharma (Inst)

Changan Sun

Employment: Jiangsu Hansoh Pharmaceutical Group Co, Ltd

Leadership: Jiangsu Hansoh Pharmaceutical Group Co, Ltd

Hongying Wei

Employment: Hansoh Pharma

Chuan Li

Employment: Hansoh Pharma

Siraj M. Ali

Employment: EQRX, EQRX

Leadership: Incysus, Elevation Oncology, Pillar Biosciences, Droplet Biosciences

Stock and Other Ownership Interests: Exelixis, Merus NV, Pfizer, Pfizer

Consulting or Advisory Role: Azitra, Princeptx, Archer

Patents, Royalties, Other Intellectual Property: patents via Foundation Medicine, patents via Seres Health on microbiome stuff in non-neoplastic disease

Vincent A. Miller

Employment: Foundation Medicine, EQRX

Leadership: Revolution Medicines

Stock and Other Ownership Interests: Foundation Medicine, Mirati Therapeutics, Revolution Medicines, EQRX

Patents, Royalties, Other Intellectual Property: Received periodic royalties related to T790M patent awarded to the Memorial Sloan Kettering Cancer Center

Qiong Wu

Employment: Hansoh Pharma

No other potential conflicts of interest were reported.

Figures

FIG 1.

Kaplan-Meier estimates of PFS. The duration of PFS by investigator assessment is estimated via Kaplan-Meier methods. In tandem, hazard in the aumolertinib arm divided by the hazard in the gefitinib arm provided the hazard ratio. For the patients who discontinued study treatment or received new antitumor therapy treatment before progression or death, the patient was censored at the latest evaluable examination date of imaging before the discontinuation date or the date of starting new antitumor therapies. HR, hazard ratio; mPFS, median PFS; PFS, progression-free survival.

FIG 2.

PFS by subgroup analysis. PFS was estimated as shown in Figure 1 for the following prespecified subgroups: EGFR mutation type, brain/CNS metastases status, sex, age, smoking history, baseline ECOG PS, and mutation test methods. ECOG PS, Eastern Cooperative Oncology Group performance status; HR, hazard ratio; PFS, progression-free survival.

FIG 3.

Kaplan-Meier estimates of PFS by stratification factors. PFS was estimated as shown in Figure 1 for the following prespecified groups: (A) patients with EGFR exon 19 deletion, (B) patients with EGFR L858R, (C) patients with CNS metastases, and (D) patients without CNS metastases. HR, hazard ratio; mPFS, median PFS; NA, not applicable; PFS, progression-free survival.