Testing Real-World Efficacy and Safety of Dacomitinib in EGFR-Mutant NSCLC

A real-world study published in Nature demonstrates the promising efficacy and safety profile of dacomitinib as a first-line treatment in patients with epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC), with a high objective response rate and median progression-free survival of 16.7 months.

Dacomitinib, a second-generation EGFR tyrosine kinase inhibitor (TKI), has demonstrated superior efficacy in clinical trials compared to first-generation EGFR TKIs such as gefitinib. Following the success of clinical trials such as ARCHER 1050, dacomitinib has been approved by the US Food and Drug Administration (FDA) as a first-line treatment for patients with NSCLC and EGFR mutations. However, real-world data is limited, especially regarding its efficacy in patients with brain metastasis. This retrospective study aimed to provide insights into the real-world effectiveness and safety of dacomitinib as a first-line treatment and to explore subsequent treatment options for patients with disease progression.

Between January 6, 2021, and December 9, 2022, 153 patients received dacomitinib as a first-line treatment, with the median age at diagnosis being 64.6 years, 60.8% female, and 68.6% never-smokers. Adenocarcinoma was the most common pathology, with stage IV diagnosis in 64.7% of patients. Exon 19 deletions and L858R mutations in exon 21 were observed in a significant portion of the population. At the initiation of dacomitinib, brain metastases were present in 45.1% of patients, with other metastatic sites also noted. The efficacy of dacomitinib included an overall response rate of 84.3% and a median progression-free survival of 16.7 months.

The safety profile of dacomitinib showed that 94.1% of patients experienced adverse events, with 7.2% reporting grade 3 or higher events. Dose reductions and interruptions were common due to adverse events, with 8.5% of patients permanently discontinuing treatment. Subsequent treatment after dacomitinib varied; some patients continued treatment beyond disease progression, while others switched to other EGFR TKIs. Tissue rebiopsy revealed the EGFR T790M mutation in a significant portion of patients who progressed on dacomitinib, leading to treatment changes such as switching to osimertinib or lazertinib. Additional resistance mechanisms beyond T790M were also explored, including C-MET expression and TP53 mutations.

Dacomitinib showed durable efficacy and manageable safety in patients with EGFR-mutated NSCLC, with common dosing reductions. Patients with brain metastases demonstrated an 84.3% overall response rate and 16.7 months median progression-free survival, superior to outcomes in ARCHER 10508. Dacomitinib showed superior survival outcomes due to comprehensive care. The study provided insight into dacomitinib efficacy, with lower IC50 values than gefitinib and a low incidence of T790M mutation in patients with disease progression.

“With a tolerable safety profile and superior survival efficacy compared with previous prospective studies, [dacomitinib] is anticipated to be a valuable second-generation EGFR TKI in clinical practice. Additionally, the study highlights its efficacy in patients with brain metastasis, establishing it as one of the viable treatment options for NSCLC patients with brain metastasis,” researchers said. 

Reference
Shin J E, Jung H A, Park S, et al. Real-world data of dacomitinib as first-line treatment for patients with EGFR-mutant non-small-cell lung cancer. Sci Rep. 2025;15(4593). doi:10.1038/s41598-024-81704-4