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Metastatic NSCLC — Targetable Driver, First-Line
Metastatic NSCLC
targetable driver
on broad NGS
EGFR ex19 / L858R
EGFR exon 20 ins
EGFR atypical
ALK
ROS1
BRAF V600E
MET exon 14
RET fusion
NTRK fusion
KRAS G12C
HER2 (ERBB2)
Preferred
Osimertinib
FLAURA ↗
CNS
Intensified
Chemo + osimertinib
FLAURA2 ↗
Chemo-free
Amivantamab + lazertinib
MARIPOSA ↗
CNS
Targeted
Amivantamab + chemo
PAPILLON ↗
TKI
Afatinib or osimertinib
context-dependent ↗
Preferred
Lorlatinib
CROWN ↗
CNS
Alternative
Alectinib
ALEX ↗
CNS
TKI
Entrectinib / repotrectinib
TRIDENT-1 ↗
CNS
Targeted
Dabrafenib + trametinib
or encorafenib + binimetinib ↗
TKI
Capmatinib / tepotinib
GEOMETRY ↗
TKI
Selpercatinib / pralsetinib
LIBRETTO-001 ↗
CNS
Tumor-agnostic
Larotrectinib / entrectinib
NAVIGATE / STARTRK ↗
CNS
Later-line
Sotorasib / adagrasib
CodeBreaK 200 ↗
ADC
Trastuzumab deruxtecan
DESTINY-Lung02 ↗