The preliminary safety results of an observational phase II study of concurrent use of aspirin with dabrafenib and trametinib in BRAF V600 NSCLC.

e20632 Background: Dabrafenib combined with trametinib (DabTram) is highly effective in treating BRAF V600-mutant non-small cell lung cancer (NSCLC). However, pyrexia is the most common adverse event (AE), affecting over 50% of patients and often leading to dose reductions or interruptions, significantly impacting clinical application. Aspirin, a COX inhibitor, not only reduces PGE2 to alleviate pyrexia but may also modulate resistance pathways involving PI3K-AKT-mTOR and RAS-RAF-MEK, providing additional therapeutic benefits. This study evaluates the safety and potential of concurrent aspirin use with DabTram in this population (NCT05988697). Methods: This multicenter phase II study enrolled IIIB-IV stage BRAF V600-mutant NSCLC patients between May 2023 and November 2024 across hospitals in Chongqing, China. Patients received Dabrafenib 150 mg BID, Trametinib 2 mg QD, and Aspirin 100 mg QD until progression or intolerable toxicity. Primary endpoints were progression-free survival (PFS) and pyrexia incidence. Secondary endpoints included overall response rate (ORR), disease control rate (DCR), overall survival (OS), and coronary event risk. Results: Seventeen patients (median age: 67 years; 64.7% male; 100% stage IV adenocarcinoma) were enrolled. Most (58.8%) were ex-smokers, and 41.2% had prior systemic anti-cancer therapy. After a median follow-up of 8.2 months, treatment-related AEs (TRAEs) occurred in 35.3% of patients, including pyrexia (11.8%), hiccups (5.9%), rash (5.9%), fatigue (5.9%), and oral ulcers (5.9%), all grade 1/2. Pyrexia, typically affecting over half of DabTram-treated patients, was reported in only 2 patients (1 grade 1, 1 grade 2), significantly lowering its incidence. One patient required dose reduction, and no gastrointestinal bleeding or grade ≥3 AEs were observed. Conclusions: The addition of aspirin to DabTram therapy effectively reduced the incidence of pyrexia, the most frequent AE limiting DabTram use, and minimized treatment interruptions. This innovative approach demonstrated a favorable safety profile with no new signals. Longer follow-up is needed to confirm survival benefits in BRAF V600-mutant NSCLC patients. Clinical trial information: NCT05988697 . Baseline characteristics. Demographic variable N=17(%) Median Age (min-max) 67(48-80) Sex: Female/Male 6(35.3)/11(64.7) Smoking history: Never smoked/ Ex-smoker 7(41.2)/ 10(58.8) Histology: Adenocarcinoma 17(100) Disease stage: IV 17(100) Prior systemic anti-cancer therapy: Yes/No 7(41.2)/ 10(58.8)