2025 MaTOS Lung | Session XII | Future Landscape on Different Genomics Drivers Biomarkers in IO and ctDNA Platforms

Dr. Rodriguez-Abreu covered advances in KRAS inhibition, highlighting new G12D and pan-KRAS inhibitors with strong responses, emerging ProTAC and cell therapies, and need for better biomarkers.
Dr. Borghaei addressed STK11/KEAP1/TP53 co-mutant tumors resistant to immunotherapy, highlighting CTLA-4 benefit, emerging combinations, and ongoing trials to overcome resistance.
Dr. Melosky reviewed HER2-targeted therapies in lung cancer, noting ADC approvals, strong DESTINY trial results, and promising TKIs and bispecific antibodies for HER2 mutations.
Dr. Villaruz covered BRAF non-V600E mutations, their biology, limited efficacy and toxicity of current inhibitors, emerging next-gen agents, and continued reliance on immunotherapy in NSCLC.
Dr. Piotrowska reviewed advances in EGFR exon 20 NSCLC, highlighting amivantamab, sunitinib, zipletinib results, and ongoing first-line trials likely to reshape treatment.
Dr. Gandara reviewed IO biomarkers for efficacy and toxicity, noting limits of PD-L1/TMB/MSI, new PD-L1 QCS improving benefit selection, and plasma proteomics predicting response and irAEs.
Dr. Rotow highlighted ctDNA’s role in predicting lung cancer outcomes and guiding therapy, noting strong NPV in trials but stressing need for prospective studies to standardize use.

The Q & A session reviewed osimertinib use in ctDNA-positive patients, MRD prognostic value, biomarker and assay variability, and challenges of de-escalation without strong predictive data.