571P - Dacomitinib in treatment-naïve EGFR-mutant NSCLC patients with multiple brain metastases: Initial efficacy and safety data from a phase II study

Background

Brain metastases (BM) are common among EGFRm NSCLC patients. And it has been associated with treatment failure and limited survival especially patients with multiple BMs. Dacomitinib is a selective, irreversible, Pan-HER TKI. It brought significant PFS and OS improvement compared with Gefitinib in phase 3 randomize study ARCHER 1050. However, patients with BM or leptomeningeal metastases were excluded in this study. We hereby conducted this phase II study (NCT02047747) to prospectively evaluate the efficacy and safety of Dacomitinib in NSCLC patients with multiple BMs and here are initial results of this study.

Methods

Treatment-naive stage IIIB/IV EGFR-mutant NSCLC patients with multiple and measurable BMs（≥ 3 metastatic lesions in the brain and at least 1 target lesion’s diameter among these lesions should be ≥1 cm） received Dacomitinib45mg orally once daily. Assessments were performed every8 weeks until disease progression (PD) as per RECIST v1.1. End points included PFS, intracranial ORR (iORR), ORR, and safety.

Results

At data cut-off (Jul 1, 2023), a total of 14 patients were enrolled and the median follow-up time was 24 months (range, 4-28m), of which 10 patients had measurable CNS response. For all patients, the mPFS was 15.3m(8/14)，ORR was 78.6% while DCR was 100%.The iORR was 80% and iDCR was 100%. The mPFS in patients with 19Del (8/14,57.1%) and21L858R (6/14,42.9%) are 15.3 and 15.2m, ORR are 87.5% and 66.7%, respectively. There are no new adverse events (AEs) compared to ARCHER1050.The most common AEs were rash (10/14; 71.4%), diarrhea (8/14; 57.1%), paronychia (3/14; 21.4%). Temporary discontinuations and dose modification occurred in 2 (14.3%) and 1 (7.1%) patient, respectively.

Conclusions

Dacomitinib showed promising intracranial antitumor activity with a manageable safety profile as first-line therapy in EGFR-mutant NSCLC patients with multiple brain metastases.

Clinical trial identification

NCT02047747.

Editorial acknowledgement

Legal entity responsible for the study

Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Funding

Pfizer.

Disclosure

Y. Yu: Financial Interests, Personal, Invited Speaker: Pfizer, AstraZeneca, Rohce, MSD. Y. Pan: Financial Interests, Personal, Advisory Board: Pfizer, AstraZeneca, Roche, MSD; Financial Interests, Personal, Invited Speaker: Pfizer. J. Zhou: Financial Interests, Personal, Invited Speaker: Pfizer, AstraZeneca, Roche, MSD. S. Lu: Financial Interests, Institutional, Invited Speaker: Hansoh, AstraZeneca, Roche, Hengrui; Financial Interests, Institutional, Advisory Board: AstraZeneca, Prizer, Boehringer Ingelheim, Hutchison MediPharma, ZaiLab, GenomiCare, Yuhan Corporation, Menarini, InventisBio Co.Ltd, Roche, Simcere Zaiming Pharmaceutical Co., Ltd.; Financial Interests, Personal, Research Grant: AstraZeneca, Hutchison, BMS, Heng Rui, Roche, Hansoh, BeiGene, Lilly Suzhou Pharmaceutical Co.Ltd; Financial Interests, Personal, Coordinating PI: FibroGen.