Efficacy and safety of dacomitinib in treatment-naïve patients with advanced NSCLC and brain metastasis: a multicenter cohort study.

BACKGROUND

The data for dacomitinib, a second-generation EGFR-TKI, treating patients with advanced non-small cell lung cancer (NSCLC) and brain metastasis was lacking. This study aimed to explore the efficacy and safety of dacomitinib in treating EGFR-mutated advanced NSCLC with brain metastasis in first-line settings.

METHODS

Eligible patients were treatment-naïve advanced NSCLC patients with ≥1 brain metastasis no less than 5 mm treated with dacomitinib. The primary endpoint was intracranial objective response rate (ORR). Secondary endpoints included intracranial and extracranial progression-free survival (PFS), overall survival (OS), intracranial and extracranial ORR, disease control rate (DCR), and safety. The response was evaluated per modified Response Evaluation Criteria in Solid Tumors (mRECIST) and RANO-BM (Response Assessment in Neuro-Oncology Brain Metastases) criteria.

RESULT

Between July 2nd, 2019, and September 30th, 2022, a total of 87 treatment-naïve patients with advanced NSCLC and brain metastasis treated with dacomitinib from four hospitals were included. The data cutoff date was March 24th, 2023, and the median duration of follow-up time was 17.5 months (range 1.6-34.7 months). Based on mRECIST criteria, for all the 87 patients with evaluable brain metastasis, the iORR was 89.7% (95%CI, 81.3%-95.2%) and iDCR was 97.7% (95%CI, 91.9-99.7%), with 42 patients achieving CR, 36 patients achieving PR, and 7 patients maintaining SD. Based on RANO-BM criteria, the iORR was 71.3% (62/87, 95%CI 60.6%-80.5%) and iDCR was 97.7% (85/87, 95%CI, 91.9%-99.7%), with 42 patients achieving CR, 20 patients achieving PR, and 23 patients maintaining SD (Table). Median iPFS was 26.0 (95%CI, 20.7-31.4) months, and the 1-year and 2-year iPFS rate were 68.9% and 51.5%, respectively. Of 75 patients with evaluable extracranial lesions, 2 patients achieved CR (2.7%), the systemic ORR was 73.8% (95%CI 63.1%-82.8%) and DCR was 96.4% (89.9%-99.3%) (Table). Systemic median PFS was 14.0 (95%CI 11.1-16.9) months and median OS was 34.0 (95%CI 28.0-39.9) months. Overall, 86 of 87 (98.9%) patients experienced adverse events (AEs) of any grade. The most common (≥20%) AEs including rash (89.7%), oral ulcer (74.2%), diarrhea (67.8%), and paronychia (59.8%). Most of the AEs were grade 1 or grade 2 and no patients died due to severe AEs.

CONCLUSIONS

Dacomitinib showed promising efficacy and a manageable safety profile for advanced NSCLC with brain metastasis harboring EGFR mutation in the first-line treatment.