Clinical Summary:

• Design/Population: A randomized phase 3 trial compared asandeutertinib with osimertinib in patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer and stable brain metastases.
• Key Outcomes: Asandeutertinib significantly improved response and survival compared with osimertinib. Safety was manageable, with no new safety concerns identified.
• Clinical Relevance: Asandeutertinib may provide a new frontline option for patients with EGFR-mutated non-small cell lung cancer and brain metastases.

Results from the phase 3 ESAONA trial demonstratd that asandeutertinib significantly improved intracranial response and intracranial progression-free survival (PFS) compared with osimertinib among patients with EGFR-mutated non-small cell lung cancer (NSCLC) and brain metastases.

These results were presented by Yuankai Shi, MD, Chinese Academy of Medical Sciences, Beijing, China, at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

In this trial, 224 patients with locally advanced or metastatic NSCLC harboring sensitizing EGFR mutations and stable brain metastases were randomized 1:1 to receive either 160 mg of once daily asandeutertinib (n = 111) or 80 mg of once daily osimertinib (n = 113). Patients were stratified based on intracranial disease burden and EGFR mutation subtype. The co-primary end points were intracranial objective response rate (ORR) and intracranial PFS, as assessed via blinded review.

At analysis, ORR was 95.5% in the asandeutertinib arm and 79.6% in the osimertinib arm (P = .0004). Investigator-assessed ORR was 92.8% and 77.9%, respectively (P = .0019), with similar findings observed using RANO-BM criteria (P = .0039).

Median intracranial PFS was not reached in the asandeutertinib arm and 17.51 months in the osimertinib arm (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.28 to 0.76; P = .0020). Investigator assessment also favored asandeutertinib (HR, 0.56; 95% CI, 0.36 to 0.89; P = 0.0122). Median overall PFS was not reached with asandeutertinib versus 17.22 months with osimertinib (HR, 0.64; 95% CI, 0.41 to 1.00; P = .0473). 

Treatment-related adverse events occurred in 99.1% of patients receiving asandeutertinib and 95.6% receiving osimertinib. Treatment-related serious adverse events were reported in 10.8% and 7.1% of patients, respectively. No new safety concerns were identified.

“Asandeutertinib significantly improved iORR and iPFS compared to osimertinib, with a manageable safety profile,” concluded Dr Shi.

Source:

Shi Y, Xing L, Zhang Z, et al.Efficacy and safety of asandeutertinib versus osimertinib as first-line treatment in EGFR-mutated NSCLC patients with brain metastases: Interim analysis of an open-label, multicenter, randomized, pivotal phase II study (ESAONA). Presented at the ASCO Annual Meeting. May 29 - June 2, 2026. Chicago, Illinois. LBA2007.