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Dacomitinib in EGFR-mutant non-small-cell lung cancer with brain metastasis: a single-arm, phase II study
1Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Introduction:
Dacomitinib showed superior progression-free survival (PFS) and overall survival compared to gefitinib in patients with advanced non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations in the ARCHER1050 study. However, because that study did not include patients with brain metastases, the efficacy of dacomitinib in patients with brain metastases has not been clarified.
Patients And Methods:
This single-arm phase II study enrolled 30 patients with treatment-naïve advanced NSCLC harboring activating EGFR mutations from January 2021 to June 2021 and started them on dacomitinib (45 mg/day). All patients had non-irradiated brain metastases with a diameter of ≥5 mm. The primary endpoint was confirmed intracranial objective response rate (iORR).
Results:
Patients had exon 19 deletions (46.7%) and L858R mutations in exon 21 (55.3%). The confirmed iORR was 96.7% (29/30), with an intracranial complete response of 63.3%. Median intracranial PFS (iPFS) was not reached, with 12- and 18-month iPFS rates of 78.6% [95% confidence interval (CI) 64.8% to 95.4%] and 70.4% (95% CI 54.9% to 90.1%), respectively. In the competing risk analysis, the 12-month cumulative incidence of intracranial progression was 16.7%. Regarding the overall efficacy for intracranial and extracranial lesions, the overall ORR was 96.7%, and the median PFS was 17.5 months (95% CI 15.2 months-not reached). Grade 3 or higher treatment-related adverse events were reported in 16.7% of patients, and 83.3% required a reduced dacomitinib dose to manage adverse events. However, none permanently discontinued dacomitinib treatment due to treatment-related adverse events.
Conclusions:
Dacomitinib has outstanding intracranial efficacy in patients with EGFR-mutant NSCLC with brain metastases.
Insights
Dacomitinib demonstrated high efficacy in treating advanced non-small-cell lung cancer (NSCLC) with EGFR mutations and brain metastases. The drug showed a 96.7% intracranial objective response rate, offering a promising option for these patients.
Area of Science:
- Oncology
- Medical Research
- Pharmacology
Background:
- Dacomitinib previously showed superior survival outcomes compared to gefitinib in advanced EGFR-mutant NSCLC.
- Efficacy of dacomitinib in patients with brain metastases remained unclear due to prior study exclusions.
Purpose of the Study:
- To evaluate the intracranial efficacy of dacomitinib in treatment-naïve patients with advanced EGFR-mutant NSCLC and brain metastases.
- To determine the intracranial objective response rate (iORR) as the primary endpoint.
Main Methods:
- A single-arm phase II study enrolled 30 patients with EGFR-mutant NSCLC and non-irradiated brain metastases.
- Patients received daily dacomitinib (45 mg).
- The primary endpoint was confirmed intracranial objective response rate (iORR).
Main Results:
- A 96.7% confirmed iORR was observed, with 63.3% complete intracranial response.
- Median intracranial progression-free survival (iPFS) was not reached; 12- and 18-month iPFS rates were 78.6% and 70.4%.
- Overall response rate was 96.7%, with a median PFS of 17.5 months. Grade 3+ adverse events occurred in 16.7% of patients.
Conclusions:
- Dacomitinib exhibits outstanding intracranial efficacy in EGFR-mutant NSCLC patients with brain metastases.
- The drug represents a significant therapeutic advancement for this patient population.
- Further research may explore long-term outcomes and optimal dosing strategies.
