medwireNews: First-line treatment with the third-generation EGFR–tyrosine kinase inhibitor aumolertinib significantly improves progression-free survival (PFS) relative to gefitinib in people with advanced non-small-cell lung cancer (NSCLC) and sensitizing EGFR mutations, indicate Chinese trial data.
In the double-blind, phase 3 AENEAS study, median PFS was 19.3 months for the 214 patients with treatment-naïve locally advanced or metastatic disease who were randomly assigned to receive aumolertinib 110 mg/day.
This was significantly longer than the 9.9- month median PFS achieved by their 215 counterparts who instead received gefitinib 250 mg/day, and equated to a 54% reduction in the risk for progression or death in favor of aumolertinib.
The 1-year PFS rates in the aumolertinib and gefitinib groups were 69.5% and 46.3%, respectively, while the corresponding rates at the 2-year mark were 32.5% and 12.9%.
The research team – led by Shun Lu, from Shanghai JiaoTong University in China – also notes that “[a]umolertinib demonstrated a consistent PFS benefit across all prespecified stratification factors, namely, EGFR mutation type and the presence or absence of known or treated [central nervous system] metastases.”
The investigators additionally report in the Journal of Clinical Oncology that the objective response rate (73.8 vs 72.1%) and disease control rate (93.0 vs 96.7%) were comparable between the aumolertinib and gefitinib groups, but the median duration of response was significantly longer with the third-generation agent, at 18.1 versus 8.3 months.
And the overall survival data were not mature at the time of analysis.
Aumolertinib was well tolerated, say Lu and colleagues, especially with regard to “[t]oxicities believed to be mediated by the inhibition of wild-type EGFR,” which occurred less frequently in the aumolertinib than gefitinib study arm.
Specifically, the incidence of any-grade rash and diarrhea was significantly lower among aumolertinib- than gefitinib-treated patients, at rates of 23.4% versus 41.4% and 16.4% versus 35.8%, respectively.
These findings align with preclinical data suggesting “that the primary metabolite of aumolertinib retains comparable selectivity for mutant over wild-type EGFR as the parent compound,” comment the study authors.
Treatment-emergent adverse events (AEs) of grade 3 or worse occurred in a comparable 36.4% of patients in the aumolertinib group and 35.8% of those in the gefitinib group. The incidence of serious AEs was also similar between groups (22.0 vs 21.4%), as was the proportion of patients requiring a dose reduction due to AEs (4.2 vs 4.7%).
But fewer patients given aumolertinib had an AE-related dose interruption (16.8 vs 24.7%) and the rate of AE-related discontinuation was also lower with aumolertinib than gefitinib (3.7 vs 5.1%).
“Given the approval of only one third-generation EGFR inhibitor [osimertinib], there is a standing need for another highly efficacious and well-tolerated agent to diversify the treatment armamentarium,” say Lu et al, adding that the AENEAS results support “the possible use of aumolertinib as first-line treatment for EGFR-mutant NSCLC.”
They continue: “Additional studies of aumolertinib are ongoing in the adjuvant setting […] and in the metastatic setting in combination with chemotherapy.”
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