Prospective phase 2 data demonstrated that aumolertinib, followed by salvage stereotactic radiation therapy, elicited responses in patients with intracranial oligometastatic EGFR-mutant non–small cell lung cancer.
Aumolertinib demonstrated central nervous system (CNS) activity when used in combination with stereotactic radiation therapy (SRT) to treat patients with intracranial oligometastatic EGFR-mutant non–small cell lung cancer (NSCLC), according to data from a prospective phase 2 study (NCT04519983) presented at the 2023 European Lung Cancer Conference (ELCC).1
After oral administration of the third-generation EGFR tyrosine kinase inhibitor (TKI), efficacy-evaluable patients (n = 32) experienced an intracranial objective response rate (iORR) of 100%, which included 3 complete responses (CRs) and 29 partial responses (PRs). The intracranial disease control rate (iDCR) was also 100%. Notably, no grade 3 or higher toxicities were observed following continued treatment with aumolertinib.
“Aumolertinib has promising efficacy and good tolerability in intracranial oligometastatic EGFR mutated NSCLC,” lead study author Jiayan Chen, MD, of Fudan University Shanghai Cancer Center in China, and colleagues, wrote in a poster on the data.
Preliminary data from this trial were previously presented at the 2022 ESMO Asia Congress, and showed that with a median follow-up time that ranged from 3 months to 12 months, the agent produced an iORR of 100% in the 8 patients enrolled. Both intracranial and extracranial lesions experienced a PR, and no patients required SRT at the time of the data cutoff date, which was June 22, 2022.2
The trial enrolled patients between the ages of 18 and 75 years who were EGFR TKI–naïve and had histologically confirmed NSCLC.1 Additional inclusion criteria included having stage IV disease with intracranial metastases at baseline, at least 1 measurable intracranial lesion according to RECIST v1.1 criteria, a life expectancy exceeding 3 months, and an ECOG performance status of 0 or 1.3 Patients were also required to have tumors that harbored EGFR exon 19 deletions and L88R mutations.
Key exclusion criteria included NSCLC EGFR driver gene negativity, previous exposure to third-generation EGFR TKIs or a major surgical procedure within 3 weeks of treatment initiation, prior palliative intracranial radiotherapy, and an inability to be assessed with magnetic resonance imaging (MRI), among others.3
All study participants received a daily 110-mg dose of oral aumolertinib and underwent at least 1 independent MRI evaluation. After intracranial disease progression, SRT was given at a dose of 32 Gy to 40 Gy (total, 8 Gy/f). Patients with stable, controlled extracranial lesions following SRT were allowed to continue aumolertinib.
Efficacy follow-up was conducted once every 6 weeks. Six weeks after initial evaluation, CR, PR, and stable disease rates were re-evaluated. Once investigator-confirmed disease progression occurred, survival follow-up was conducted once every 3 months.
The trial’s primary end point was iORR. Key secondary end points included intracranial progression-free survival, intracranial duration of response according by RECIST 1.1 criteria, cerebral radiation necrosis rate, and overall survival. Investigators also evaluated safety according to Common Terminology Criteria for Adverse Events version 5.0.
At the 2023 ELCC, investigators shared updated findings from the open-label, single-arm, prospective trial. The data cutoff date for the analysis was January 26, 2023.
At this timepoint, a total of 35 patients were enrolled in the trial; 32 of these patients were deemed evaluable and were followed for 3 to 16 months. The median age in all patients was 60 years (range 36-81). Additionally, 15 patients were male and 20 were female. Twelve patients were current or former smokers and 23 were never smokers. In terms of ECOG performance status, 22 patients had a status of 0, and 13 had a status of 1. All patients had adenocarcinoma. Regarding mutational status, 19 patients harbored an EGFR exon 19 deletion mutation, and 16 harbored an EGFR L858R mutation.
Twelve months after the initiation of aumolertinib, 1 patient experienced intracranial progression of the primary lesion but had stable extracranial lesions; this patient was subsequently treated with SRT.
Safety analysis showed that continued oral administration of aumolertinib did not produce any grade 3 or greater adverse effects (AEs). Notably, 1 patient experienced grade 2 creatine phosphokinase elevation.
The most common AEs of any grade observed in at least 20% of patients included rash (n = 5), increased alanine aminotransferase (n = 2), increased aspartate aminotransferase (n = 2), decreased white blood cell count (n = 1), decreased platelet count (n = 1), constipation (n = 1), and increased blood creatinine phosphokinase (n = 1).