Stage 4 lung cancer with driver mutations

 1. RET mutated: First line selpercatinib or pralesitinib based on phase III trial showing better PFS ( 24 m versus 12 m) , ORR 84 vs 64% compared to chemo+pembro. SE: LFT abnormalities, Qtc prolongation and hypertension. Diarrhea, dry mouth, fatigue, Low plt.

2. NTRK mutated: < 1% of all stage 4 lung ca.  larotrectinib typically administered at 100 mg orally twice daily for adults, and entrectinib at 600 mg daily

3. EGFR exon 19 deletion, exon 21 L858R mutation are the most common types. If T790M mutation is identified de novo without prior EGFR rx, do germline testing.

4. BRAF: dabrafenib+ trametinib or encorafenib+ binimetinib

5. cMET- capmatinib, tepotinib, crizotinib, for high CMET--> telisotuzumab ( ADC)

Six serious side effects of bevacizumab: Hypertension, arterial embolism including stroke, MI, reversible posterior leukoencephalopathy syndrome, bowel perforation, proteinuria