EGFR-mutated non-small-cell lung cancer: lines of therapy

Cancer page →

6 standard-of-care settings across 3 lines and 3 biomarker subgroups. Rows come from the cancer page's standard of care; the grid places each on its line and subgroup.

Line	All comers	EGFR exon 20	KMT2A
Locally advanced	1	·	·
Advanced, first line	2	1	·
Other settings	1	·	1

Locally advanced

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
All comers	Unresectable stage III	Concurrent platinum chemoradiation followed by osimertinib until progression (LAURA) rather than durvalumab.	OsimertinibLAURAChemoradiation (chemoradiotherapy, CRT)IMRT / IGRT (modern external beam)	NCCN Guidelines: Non-Small Cell Lung Cancer	93

Advanced, first line

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
All comers	Advanced, first line (exon 19 deletion or L858R)	Osimertinib alone (FLAURA), osimertinib plus platinum-pemetrexed (FLAURA2) for patients with high burden or brain metastases who can take chemotherapy, or amivantamab plus lazertinib (MARIPOSA) with prophylaxis against rash and clots.	OsimertinibFLAURAFLAURA2AmivantamabLazertinibAmivantamab + lazertinib (first-line EGFR NSCLC)MARIPOSAEGFR exon 19 deletion & L858R	NCCN Guidelines: Non-Small Cell Lung Cancer	88
All comers	Advanced, after osimertinib	Biopsy or plasma test for the mechanism: osimertinib plus savolitinib for MET amplification; otherwise amivantamab plus platinum chemotherapy (MARIPOSA-2), platinum-pemetrexed, or datopotamab deruxtecan after chemotherapy; platinum-etoposide for small-cell transformation.	AmivantamabA Study of Amivantamab and Lazertinib in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non- Small Cell Lung Cancer After Osimertinib FailureSavolitinibOsimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior OsimertinibDatopotamab deruxtecanTROPION-Lung05MET amplification (bypass resistance)EGFR C797SHistologic transformationPlatinum + etoposide (EP / CE)	NCCN Guidelines: Non-Small Cell Lung Cancer	91
EGFR exon 20	Advanced, exon 20 insertion	Amivantamab plus carboplatin-pemetrexed first line (PAPILLON); sunvozertinib after platinum chemotherapy.	AmivantamabA Study of Combination Amivantamab and Carboplatin-Pemetrexed Therapy, Compared With Carboplatin-Pemetrexed, in Participants With Advanced or Metastatic Non-Small Cell Lung Cancer Characterized by Epidermal Growth Factor Receptor (EGFR) Exon 20 InsertionsSunvozertinibAssessing an Oral EGFR Inhibitor, Sunvozertinib in Patients Who Have Advanced Non-small Cell Lung Cancer With EGFR or HER2 Mutation (WU-KONG1)EGFR exon 20 insertionCarboplatinPemetrexed	NCCN Guidelines: Non-Small Cell Lung Cancer	86

Other settings

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
All comers	Resected stage IB to IIIA	Surgery, adjuvant platinum chemotherapy where indicated, then three years of osimertinib (ADAURA).	OsimertinibADAURALobectomyNeoadjuvant / adjuvant / perioperative	NCCN Guidelines: Non-Small Cell Lung Cancer	87
KMT2A	Brain and leptomeningeal metastases	Osimertinib has high brain penetration and is preferred; stereotactic radiosurgery for symptomatic or large lesions; high-dose osimertinib for leptomeningeal disease.	OsimertinibStereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS)Brain metastases (intracranial disease)Leptomeningeal disease	NCCN Guidelines: Non-Small Cell Lung Cancer	87

Lines and subgroups are parsed from the setting text of each standard-of-care row and can misclassify an unusual phrasing; the row’s own setting is always shown. Guideline chips reflect the NCCN category and ESMO-MCBS grade recorded on the cancer page, checked on its stated date. Not medical advice.