Abstract 82P
Background
In non-small cell lung cancer (NSCLC) resistance to immunotherapy and targeted therapy remain an unmet need. Methylthioadenosine phosphorylase (MTAP) deletion emerged as a promising therapeutic vulnerability present in 15% of solid tumors including NSCLC. This study characterizes demographic, clinical, and molecular features, treatment modalities, and real-world overall survival (rwOS) in advanced NSCLC patients, stratified by MTAP deletion status.
Methods
The Flatiron Health Foundation Medicine Clinico Genomics database included patients diagnosed with advanced (Stage 3b -IV) NSCLC who fulfilled the following criteria: (1) diagnosis between January 1, 2011 and September 30, 2021; (2) 6 months of allowable follow-up data; (3) NGS testing of tumor tissue. Index date was defined as line of therapy start date.
Results
MTAP deletion was observed in 16.2% (895/5516) of the study population. MTAP cohorts had comparable demographic and clinical characteristics, including age, race and sex. Patients were largely treated in community-based settings, presented with non-squamous histology and had advanced stage at diagnosis. The proportion of patients with smoking history was numerically lower in the MTAP deleted group (80%) compared to those in the WT group (87%). Median rwOS in first-line therapy (anchored on start of 1L treatment) and second-line therapy (anchored on start of 2L treatment) was similar among MTAP deleted and WT groups, 13.4 (95% CI 11.3–15.2) vs 13.4 (95% CI 12.3–14.4) months (first-line), and 10.9 (95% CI 8.0–14.2) vs 9.8 (95% CI 8.0–11.0) months (second-line).
Conclusions
MTAP deletion in patients with advanced NSCLC does not appear to exhibit a strong association with overall outcomes under the current treatment modalities. MTAP deletion has emerged as a potential target for MTA-cooperative PRMT5 inhibitors in advanced NSCLC. The potential of these agents as a targeted therapy is considerable particularly given the frequency of MTAP deletion across genomic subsets of NSCLC. Further research into this evolving biomarker will be key to the optimal development of these novel agents.
Legal entity responsible for the study
Amgen.
Funding
Amgen.
Disclosure
A. Sacher: Financial Interests, Institutional, Invited Speaker: Genentech-Roche, BMS, AstraZeneca, Amgen, Iovance, CRISPR Therapeutics, Merck, Pfizer, GSK, Spectrum, Lilly, BridgeBio, Hotspot Therapeutics; Non-Financial Interests, Personal, Advisory Role, Advisory committee (no personal fees).: Amgen, Merck, Genentech-Roche; Other, Personal, Other, Travel to clinical trial investigator meeting.: Genentech-Roche, Amgen, Merck. M. Clouser: Financial Interests, Personal, Stocks/Shares: Amgen; Financial Interests, Institutional, Full or part-time Employment: Amgen; Financial Interests, Personal and Institutional, Project Lead: Amgen. A. Balasubramanian, E.H. Elkhouly, P. Martinez: Financial Interests, Personal and Institutional, Full or part-time Employment: Amgen; Financial Interests, Personal and Institutional, Stocks/Shares: Amgen. A. Hindoyan, X. Zhang, B.E. Sylvester, J. Hildebrand: Financial Interests, Personal and Institutional, Stocks/Shares: Amgen; Financial Interests, Personal and Institutional, Full or part-time Employment: Amgen. M. Villalona: Other, Institutional, Other, Travel to clinical trial meeting: Amgen.