Dacomitinib in the treatment of EGFR-mutated non-small cell lung cancer with brain metastases: an open-label, multicenter, phase II study.

OBJECTIVES

Dacomitinib's efficacy in patients with severe brain metastases remains understudied. This study aimed to evaluate dacomitinib in treatment-naïve non-small-cell lung cancer (NSCLC) patients with EGFR mutations and multiple brain metastases.

METHODS

This open-label, multicenter, Phase II study enrolled 15 treatment-naïve NSCLC patients with ≥3 brain metastases, including at least one lesion >1 cm. Patients received dacomitinib 45 mg/day orally. Primary endpoints included progression-free survival (PFS), while secondary endpoints encompassed objective response rate (ORR), disease control rate (DCR), intracranial ORR (iORR), intracranial PFS (iPFS), and the incidence of treatment-emergent adverse events (TEAEs). Exploratory analyses were conducted to evaluate the influence of different types of EGFR mutations on the clinical outcomes. This study was registered in ClinicalTrials.gov (NCT04339829) and is closed to accrual.

RESULTS

The median PFS was 16.8 months (95 % CI: 15.376, NE), with an overall ORR of 93.3 % (95 % CI: 68.052 %, 99.831 %) and DCR of 100 %. Intracranial efficacy was notable, with an iORR of 66.7 % (95 % CI: 38.380 %, 88.176 %) and median iPFS of 16.6 months (95 % CI: 3.614, NE). Among patients evaluated for intracranial response, the iORR reached as high as 90.9 %. Exploratory analyses revealed no significant differences in PFS, iPFS, or disease progression based on exon 19 deletions or L858R mutations. Six patients (40 %) experienced ≥grade 3 TEAEs which were manageable.

CONCLUSION

Dacomitinib demonstrated robust systemic and intracranial efficacy in patients with NSCLC harboring EGFR mutations and severe brain metastases, with acceptable adverse events, thereby supporting its use as a first-line treatment.