afatinib

Overview

Afatinib is an irreversible, pan-ErbB (EGFR/HER2/HER4) tyrosine kinase inhibitor (2nd-generation EGFR TKI) approved for EGFR-mutant non-small cell lung cancer. It covalently binds to EGFR, HER2, and HER4, distinguishing it from reversible 1st-generation TKIs.

Evidence in the corpus

• BRAF fusions are a recurrent (2–4%) mechanism of acquired resistance to EGFR TKIs including afatinib in EGFR-mutant LUAD; median time from EGFR TKI start to acquired BRAF fusion detection was 23 months (range 9–37 months) across 15 patients PMID:38922339.
• NCI-60 CellMiner pharmacogenomics analysis identified genomic determinants of afatinib (pan-EGFR TKI) sensitivity in colon cancer cell lines PMID:22802077
• Clinical benefit in EGFR kinase domain duplication (EGFR-KDD) and L861Q EGFR alleles in 860-patient MSK-IMPACT LUAD cohort; allele-specific response data support afatinib/osimertinib over first-generation TKIs for atypical EGFR alleles including L861Q PMID:28336552.

Resistance mechanisms

• Acquired BRAF fusions emerge after afatinib therapy in EGFR-mutant LUAD as a bypass resistance mechanism PMID:38922339.

Cancer types (linked)

• LUAD

Sources

• PMID:38922339

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