Abstract 668P
Background
Methylthioadenosine phosphorylase (MTAP) is a key enzyme involved in the salvage pathway of purine metabolism. MTAP loss occurs in approximately 15% of non-small cell lung cancer (NSCLC). Given the prevalence of MTAP loss in NSCLC and its association with poor prognosis, targeting MTAP may represent a promising therapeutic strategy. We, therefore, aim to explore the association between MTAP loss and response to immune checkpoint inhibitors (ICI) in advanced NSCLC.
Methods
The present study was conducted as a part of an ongoing multi-center prospective precision oncology genomic sequencing programme in Hong Kong. Comprehensive target panel next-generation sequencing (cTP-NGS) was performed using Foundation One CDx in newly diagnosed advanced non-squamous NSCLC. The genomic landscape of MTAP-loss and MTAP-proficient tumors was described. We compared the clinical characteristics, genomic landscape, and survival outcomes of patients harboring MTAP-loss and MTAP-proficient tumors.
Results
205 consecutively recruited patients were analyzed. MTAP loss was observed in 18% (n=37) of our cohort. MTAP loss was correlated with never-smokers (p = 0.034), and negative PD-L1 expression (TPS <1%) (p = 0.00022). There was no significant association with age, gender, actionable alterations, and TMB in the MTAP loss cohort. EGFR was the most frequently altered gene (Loss: 46% vs Proficient: 35%). CDKN2A/B loss was comutated with MTAP loss, while TEK loss was only reported in 19% of MTAP loss. The median follow-up time was 14 months. Among patients who received systemic therapy, the median OS (mOS) of the MTAP loss and proficient cohorts was 24.9 and 22.5 months (p = 0.95), respectively. However, among the patients who received ICI +/- chemotherapy (n=56), the mOS in the MTAP loss cohort was 6.3, while the mOS was 27.6 months in the MTAP proficient cohort (HR: 3.31; 95% CI: 1.21-9.04; p = 0.020).
Conclusions
Our study underscores the clinical significance of MTAP loss and its association with poor response to ICIs in advanced-stage NSCLC. These findings highlight the potential prognostic value of MTAP status in patients who receive ICI +/- chemotherapy and suggest that MTAP loss may be a predictor of poorer outcomes.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Innovation and Technology Commission (ITC)–Hong Kong under the Partnership Research Programme scheme (PRP/067/20FX).
Disclosure
All authors have declared no conflicts of interest.