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Identifying Atypical EGFR Alterations and Personalizing First-line Treatment

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This activity is available for 0.50 CME/CE credit(s).

Released: November 13, 2026

Expiration: May 12, 2027

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1 Pre Assessment 2 Video 3 Post Assessment 4 Evaluation 5 Credit

Atypical EGFR mutations in NSCLC are less common than classical mutations and tend to have worse outcomes. In this video module, an expert discusses the latest evidence and guideline recommendations for frontline therapy with afatinib, osimertinib, or amivantamab plus lazertinib for atypical EGFR mutations. Options for EGFR exon 20 insertion mutations are discussed, including amivantamab plus chemotherapy and sunvozertinib. A brief overview of treatments for classical mutations is covered for context.

Alexander Spira
Alexander Spira, MD, PhD, FACP
Atypical EGFRm NSCLC 1L tx

Pre Assessment

Assess your current knowledge and clinical approach before beginning your video.
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1.

How many people with NSCLC do you provide care for in a typical month?

2.

For those who practice in academic or community settings, please indicate your practice setting

3.

A 69-year-old woman with newly diagnosed metastatic lung adenocarcinoma undergoes comprehensive NGS testing to inform first-line treatment selection. She has an ECOG PS of 1, no brain metastases, and adequate organ function. Molecular profiling found EGFR G719A (VAF = 21%) and L861Q (VAF = 19%) mutations, no alterations in ALK, ROS1, or RET and no MET amplification. The PD-L1 TPS score is 60%.

Which of the following is the most appropriate interpretation of the patient’s NGS results to guide first-line treatment selection?

4.

Along with afatinib, which one of the following treatment options is included in recent ASCO guidelines as a first-line therapy option for a patient with an atypical EGFR mutation (S786I, L861Q, G719X)?

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