Rare EGFR exon insertions in lung cancer allow targeted therapies, but resistance develops; new drugs help.

EGFR exon insertion mutations in lung cancer are rare – exon 19 insertions occur in just 1% of EGFR mutations and exon 20 in 4%. These mutations define specific subtypes of NSCLC. While exon mutations cause faster tumor growth, they also allow for targeted therapy with EGFR inhibitor drugs rather than just chemotherapy. For exon 19, FDA-approved treatments like Gilotrif and Tagrisso block signals needed for growth. But exon 20 tumors are often resistant, so new targeted drugs like Rybrevant and Exkivity now provide options. Overall, these mutations have a poor prognosis as resistance develops. But growing treatment options aimed at the specific exon genetic variants offer hope to prolong and improve quality of life.

Lung cancer genetic testing is critical, especially for never-smokers and adenocarcinomas, to identify targetable mutations like exon insertions. While insertion mutations increase tumor growth signals, the trade off is that they allow matched targeted therapies. Exon 19 insertions can be treated by several FDA-approved EGFR inhibitors that block growth signaling. But exon 20 mutations have shown resistance, limiting treatment options until recently. Within the last year, two new targeted drugs – Amivantamab and Mobocertinib – were approved specifically for exon 20 metastatic NSCLC.

In summary, EGFR exon insertion mutations, though rare, define NSCLC subtypes amenable to newer targeted treatments. Testing is crucial to match tumor variants to precision therapy rather than one-size-fits-all chemo. Exon 19 insertions respond to approved EGFR inhibitors, while the resistant exon 20 subtype now has new targeted drugs after years of limited options. Genetic profiling is expanding possibilities for targeted therapy in these rare mutation subtypes within NSCLC.

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