Dr. Karim presented Case 1, a 76-year-old with ROS1 fusion NSCLC showed progression on entrectinib due to resistance mutation; panel favored teletrectinib and stressed careful sequencing and diagnosis. Case 2, presented by Dr. Gainor was a 66-year-old woman with RET fusion lung adenocarcinoma received RT. Panel favored selpercatinib for efficacy, CNS activity, and lower pneumonitis risk. Dr. Das presented Case 3, a 60-year-old never-smoker with metastatic adenosquamous lung cancer and high PD-L1 responded dramatically to capmatinib after MET14 mutation discovery, highlighting value of targeted therapy. Case 4, presented by Dr. Bazhenova was of a 26-year-old with HER2 exon 20 lung cancer relapsed after chemo and zangertinib; panel debated next steps including T-DXd and emerging therapies. Dr. Sanborn presented Case 5, a 67-year-old with BRAF V600E metastatic lung cancer had durable control on BRAF/MEK therapy. With slow progression, panel debated continuing targeted therapy versus switching. Dr. Alder presented Case 6, a 56-year-old with NTRK fusion lung cancer was treated with larotrectinib. Panel stressed RNA testing to avoid missed fusions and guide targeted therapy. The wrap up panel discussion reviewed post-targeted therapy progression, stressing resistance mechanisms like MET amplification, value of rebiopsy, individualized use of chemo, TKIs, IO, and trials.