Abstract 574P
Background
Common EGFR mutations showed marked sensitivity to different generations of EGFR tyrosine kinase inhibitors (EGFR-TKIs), while uncommon mutations showed heterologous responses to EGFR-TKIs. Dacomitinib, a highly selective, irreversible second-generation EGFR-TKI, showed a significant improvement in progression-free survival (PFS) in treating patients with EGFR-mutation-positive NSCLC. This study aimed to explore the efficacy and safety of dacomitinib in treating uncommon EGFR-mutated advanced NSCLC.
Methods
Treatment-naïve advanced NSCLC patients treated at Hunan Cancer Hospital were retrospectively evaluated. Eligible patients were pathological confirmed unresectable stage III or stage IV NSCLC with uncommon EGFR mutation (mutation other than exon 19 deletion and 21 L858R); with at least one measurable target lesion; receiving dacomitinib as first-line therapy. All patients were treated with dacomitinib. Initial doses of dacomitinib were 35 mg or 45 mg per day. The primary endpoint was PFS. Secondary end points included overall survival, objective response rate, disease control rate and safety.
Results
Between December 2019 and December 2021, a total of 16 patients with uncommon EGFR-mutated NSCLC was included. There were nine (56.3%) patients harboring 18 G719X mutation, four (25.0%) with 21 L861Q, two (12.5%) with 21 L833V/H835L and one (6.3%) with 19 delins. For whole cohort, median PFS was 14.0 (95% CI 4.32-23.7) months, and median OS was not reached. ORR was 68.8% (95% CI 41.3 to 89.0%) and DCR was 93.8% (95%CI 69.8 to 99.8%), including three achieving complete remission (CR) and eight achieving partial remission (PR). Median PFS for patients with brain metastasis was 9.0 (95%CI 6.9 to 11.1) months. For patients with brain metastasis, intracranial ORR was 100%, including 2 CR and 4 PR. Major treatment-related adverse events included rash (87.5%), paronychia (62.5%), oral ulcers (50.0%), and diarrhea (50.0%), none of which were ≥grade 3 TRAEs.
Conclusions
Dacomitinib showed good activity and manageable toxicity in NSCLC patients with uncommon EGFR mutations and could be a potential treatment option for these patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Heath Research Foundation of Chinese Society of Clinical Oncology, Hunan Provincial Natural Science Foundation of China, Project of Health and Health Commission of Hunan Province, Hunan Cancer Hospital Climb Plan, and Beijing Xisike Clinical Oncology Research Foundation.
Disclosure
All authors have declared no conflicts of interest.
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