KEY TAKEAWAYS
- The phase 2 trial aimed to investigate the efficacy and safety of dacomitinib in treating multiple BM among EGFRm NSCLC patients.
- The various endpoints were PFS,iORR, ORR, and safety.
- Researchers noticed promising intracranial antitumor activity and a manageable safety profile with dacomitinib as first-line therapy for EGFR-mutant NSCLC patients.
Brain metastases (BM) worsen the complexity and survival of brain cancer, especially when multiple tumors are present. In the case of EGFRm non small cell lung cancer (NSCLC) with multiple BM, treatment options are limited due to factors like exclusion from certain trials.
Dacomitinib, a selective Pan-HER TKI, demonstrated notable efficacy in ARCHER 1050 but excluded BM patients. The phase II study (NCT02047747) prospectively assessed dacomitinib’s efficacy and safety in NSCLC patients with multiple BMs, revealing promising intracranial antitumor activity with a manageable safety profile as first-line therapy.
Yongfeng Yu and his team aimed to assess the therapeutic potential of dacomitinib in a previously excluded subset of NSCLC patients with multiple BMs.
The study analyzed treatment-naive stage IIIB/IV EGFR-mutant NSCLC patients with multiple and measurable BM (≥ 3 lesions, with at least 1 lesion ≥1 cm) who received dacomitinib at a dose of 45mg orally once daily. Assessments, conducted every 8 weeks until disease progression per RECIST v1.1, focused on endpoints including progression-free survival (PFS), intracranial overall response rate (iORR), overall response rate (ORR), and safety.
About 14 patients were enrolled in the study. As of the data cut-off on July 1, 2023, with a median follow-up of 24 months (range, 4-28 m), 10 patients exhibited a measurable central nervous system (CNS) response. The median progression-free survival (mPFS) for all patients was 15.3 months (8/14), with an overall response rate (ORR) of 78.6% and a disease control rate (DCR) of 100%. The intracranial ORR (iORR) was 80%, and the intracranial disease control rate (iDCR) was 100%. Subgroup analysis showed an mPFS of 15.3 months for patients with 19Del (8/14, 57.1%) and 15.2 months for those with 21L858R (6/14, 42.9%), with corresponding ORRs of 87.5% and 66.7%, respectively.
No new adverse events (AEs) were observed compared to ARCHER1050, and the most common AEs were rash (10/14;71.4%), diarrhea (8/14;57.1%), and paronychia (3/14; 21.4%). Temporary discontinuations and dose modifications occurred in 2 (14.3%) and 1 (7.1%) patient, respectively.
The study concluded that dacomitinib, administered as first-line therapy, demonstrates promising intracranial antitumor activity and maintains a manageable safety profile in patients with EGFR-mutant NSCLC harboring multiple BM.
The study is sponsored by David Piccioni
Source: https://cslide.ctimeetingtech.com/asia2023/attendee/confcal/show/session/78
Clinical Trial: https://clinicaltrials.gov/study/NCT02047747
Yu Y, Pan Y, Zhou J, et al. (2023). “Dacomitinib in treatment-naïve EGFR-mutant NSCLC patients with multiple brain metastases: Initial efficacy and safety data from a phase II study.” Presented at ESMO ASIA 2023 (Abstract 571P).
