Treatment of Advanced NSCLC with EGFR Exon 19 Deletion or L858R Mutation
Advanced or metastatic non-small cell lung cancer (NSCLC) harbouring an EGFR exon 19 deletion or an EGFR L858R mutation represents a molecularly defined subgroup. Identifying which mutation is present is central to selecting the appropriate clinical pathway.
Clinical Scenario
This protocol applies to patients with advanced or metastatic NSCLC confirmed to carry an EGFR exon 19 deletion mutation or an EGFR L858R mutation. These two variants together account for the large majority of all EGFR mutations encountered in NSCLC, and both are associated with responsiveness to targeted therapies directed at the EGFR pathway.
Treatment Approach
This protocol addresses subsequent therapy options for patients with disease progression. Regimen selection is guided by histological subtype, the presence of specific co-occurring findings, and prior treatment history — including whether certain agents have already been administered. The full structured evidence-based regimen, with all options and selection criteria, is available via the link below.
References
The two most common EGFR mutations in NSCLC are exon 19 deletions and L858R; these represent approximately 85% to 90% of all EGFR mutations in NSCLC.
Both result in activation of the tyrosine kinase domain and are associated with sensitivity to small-molecule EGFR tyrosine kinase inhibitors (TKIs).
Amivantamab-vmjw in combination with carboplatin and pemetrexed is a preferred treatment option for patients with multiple lesions.
Lazertinib + amivantamab-vmjw may also be useful in certain circumstances, if not previously given.
Datopotamab deruxtecan-dlnk is included on NSCL-K 5 of 6 as a subsequent therapy option for patients with nonsquamous NSCLC with EGFR mutations, including exon 19 deletions or L858R mutation.
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