Adonertinib (FHND9041) versus Afatinib as First-line Treatment for Advanced Non-small-cell Lung Cancer with EGFR Sensitive Mutation (FHND9041-Ⅲ-01): A Multi-centre, Open-label, Randomised Phase 3 Trial
Adonertinib may improve progression-free survival compared to afatinib in advanced NSCLC with EGFR sensitive mutations, but further studies are needed to confirm these findings.
Where it sits
this study against the rest of the ll-37 corpusSummary and findings
This study evaluated the efficacy and safety of adonertinib compared with afatinib in patients with advanced non-small-cell lung cancer harboring EGFR sensitive mutations. A total of 346 patients were enrolled, with 175 in the adonertinib group and 171 in the afatinib group. The median progression-free survival was 16.7 months for adonertinib and 14.5 months for afatinib.
Abstract
<title>Abstract</title> <p>Adonertinib (FHND9041) is a new third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). This multi-centre, open-label, randomised phase 3 trial evaluated the efficacy and safety of adonertinib compared with afatinib in the first-line treatment of patients with advanced non-small-cell lung cancer (NSCLC) harbouring EGFR sensitive mutations. Between November 18, 2021 and March 16, 2023, 175 patients were enrolled in the adonertinib group and 171 patients in the afatinib group. At data cutoff date of March 15, 2025, the median progression-free survival (PFS) was 16.7 months (95% CI 14.5-20.8) in the adonertinib group and 14.5 months (95% CI 12.5-16.5) in the afatinib group (HR 0.70, 95% CI 0.54-0.91; p=0.0087). The median PFS for patients with EGFR Ex19del was 26.1 months (95% CI 18.7-29.0) in the adonertinib group and 16.5 months (95% CI 14.4-18.6) in the afatinib group (HR 0.53, 95% CI 0.36-0.77; p=0.0008). The incidence of treatment-related adverse events (TRAEs) was 83.1% (143/172) in the adonertinib group and 100% (171/171) in the afatinib group. The incidence of ≥grade 3 TRAEs was 14.0% (24/172) in the adonertinib group and 36.3% (62/171) in the afatinib group. Most common ≥grade 3 TRAEs included diarrhea (0 in the adonertinib group vs 17.0% [29/171] in the afatinib group), rash (0 vs 4.7% [8/171]), mucositis oral (0 vs 3.5% [6/171]). Adonertinib significantly improved PFS with a manageable safety profile compared with afatinib in patients with previously untreated advanced NSCLC harbouring EGFR sensitive mutations, especially for EGFR Ex19del, representing a new first-line treatment option for this patient population. This study is registered with www.chictr.org.cn, ChiCTR2100050397; and ClinicalTrials.gov, NCT06759857.</p>
Background
Not reported in abstract.
Methods
Not reported in abstract.
Results
Not reported in abstract.
Interpretation
Not reported in abstract.
Limitations
Not reported in abstract.