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Treatment by Stage
- Stage I: lobectomy
- Stage II: surgery + adjuvant chemo; + atezolizumab if PD-L1+ (IMpower010); + osimertinib if EGFR+ (ADAURA)
- Stage III unresectable: chemoradiation + durvalumab (PACIFIC) or osimertinib (LAURA EGFR+)
- Stage IV: molecular profiling â targeted or IO
EGFR Treatment
- 1st-line: osimertinib (FLAURA) â 80 mg daily
- Adjuvant: osimertinib (ADAURA) Ã 3 years
- Stage III unresectable: osimertinib consolidation (LAURA 2024)
- Resistance: C797S, MET amplification, histologic transformation
ALK Treatment
- 1st-line: alectinib, brigatinib, lorlatinib (most potent)
- Trials: ALEX, ALTA-1L, CROWN
ROS1
- Crizotinib, entrectinib, repotrectinib (2023)
KRAS G12C
- Sotorasib (CodeBreaK 100), adagrasib (KRYSTAL-1)
- 35% response
HER2 Mutation
- Trastuzumab deruxtecan (DESTINY-Lung)
NTRK
- Larotrectinib, entrectinib (rare)
RET
- Selpercatinib, pralsetinib (rare)
Immunotherapy
- PD-L1 ⥠50%: pembrolizumab monotherapy
- PD-L1 < 50%: pembrolizumab + chemo
- Combo regimens: nivolumab/ipilimumab + chemo (CheckMate 9LA, 227)
Neoadjuvant Immunotherapy (NEW)
- CheckMate 816 (2022): nivolumab + chemo â pCR 24% vs 2%
- AEGEAN (2023): durvalumab + chemo
- KEYNOTE-671 (2023): pembrolizumab perioperative
Trials Landmark
- ADAURA, LAURA: osimertinib early stages
- ALEX, CROWN: ALK TKIs
- CodeBreaK 100: sotorasib KRAS G12C
- DESTINY-Lung: trastuzumab deruxtecan HER2
- PACIFIC: durvalumab stage III
- KEYNOTE-024, 189, 407: pembrolizumab in NSCLC
- IMpower010: atezolizumab adjuvant
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| EGFR |
Osimertinib |
FLAURA, ADAURA, LAURA |
| ALK |
Alectinib, lorlatinib |
ALEX, CROWN |
| ROS1 |
Repotrectinib |
TRIDENT-1 |
| KRAS G12C |
Sotorasib, adagrasib |
CodeBreaK, KRYSTAL |
| MET |
Capmatinib |
GEOMETRY-mono |
| HER2 |
Trastuzumab deruxtecan |
DESTINY-Lung |
| BRAF |
Dabrafenib + trametinib |
BRF113928 |
| NTRK |
Larotrectinib |
NAVIGATE |
| RET |
Selpercatinib |
LIBRETTO |
Special Topics
Osimertinib + LAURA Trial
- Stage III unresectable EGFR+
- After chemoradiation
- Median PFS 39.1 months (vs 5.6 months placebo)
- Game-changing 2024
Lung Cancer in Asian Women
- Often EGFR+
- Non-smokers common
- Better response to TKIs
- Distinct epidemiology