Real-world outcomes of first-line afatinib in advanced non–small cell lung cancer patients with uncommon EGFR mutations at Vietnam National Cancer Hospital.

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Background: Uncommon EGFR mutations represent a heterogeneous subgroup of non–small cell lung cancer (NSCLC) with variable responses to EGFR tyrosine kinase inhibitors (EGFR-TKIs). Real-world data, particularly from Vietnam, remain limited. This study aimed to evaluate treatment outcomes in advanced NSCLC patients harboring uncommon EGFR mutations. Methods: This retrospective single-center study included 87 patients with stage IIIC–IV lung adenocarcinoma carrying uncommon EGFR mutations treated at Vietnam National Cancer Hospital between January 2018 and September 2024, with follow-up until September 2025. Results: A total of 87 patients were enrolled, with a mean age of 61.6 ± 8.6 years. The distribution of EGFR mutations showed a predominance of major uncommon mutations (78,2%; group 1), followed by other rare uncommon mutations (14,9%; group 2), and exon 20 insertions/duplications (6,9%; group 3). The overall objective response rate (ORR) for the entire cohort was 62.1%, and the disease control rate (DCR) was 80.5%. When analyzed by mutation subgroup, the ORR in group 3 was significantly lower than in groups 1 and 2 (12.5% vs. 66.7% and 70.0%, respectively; p < 0.05), while no significant difference was observed between groups 1 and 2 ( p > 0.05). With a median follow-up of 28.1 ± 1.4 months, the median progression-free survival (mPFS) for the entire cohort was 11.3 ± 0.9 months. The mPFS for groups 1, 2, and 3 was 12.1 ± 1.3 months, 10.3 ± 3.2 months, and 3.0 ± 2.2 months, respectively. Pairwise log-rank analysis demonstrated a statistically significant difference in PFS between groups 1 and 3 (χ² = 4.846, p = 0.028). No significant differences were observed between groups 1 and 2 ( p = 0.176) or between groups 2 and 3 ( p = 0.215). The median overall survival (OS) for the entire cohort was 22.9 ± 3.1 months. Following disease progression,69% of patients received subsequent systemic therapy, most commonly platinum-based chemotherapy and/or third-generation EGFR-TKIs. Patients with exon 20 insertions were more likely to receive chemotherapy. Conclusions: Afatinib shows favorable efficacy in advanced NSCLC patients with uncommon EGFR mutations, particularly in non–exon 20 insertion subgroups, while exon 20 insertions are associated with poorer outcomes, indicating the need for alternative treatment strategies in this population.

Distribution of uncommon EGFR mutation subtypes (n = 87).