medwireNews: The sensitivity of the selective tyrosine kinase inhibitor poziotinib in people with advanced non-small-cell lung cancer (NSCLC) and EGFR exon 20 insertions is “highly dependent” on the location of the insertion, US researchers have found.
Among the 44 evaluable participants of a single-arm, phase 2 study of poziotinib 16 mg/day, the objective response rate was significantly higher for the 32 patients with insertions in the near-loop region proximal to the αC helix of exon 20 than for the 12 with insertions in the distal far-loop region, at 46% versus 0%.
And patient responses correlated directly and significantly with insertion location, report John Heymach and team from The University of Texas MD Anderson Cancer Center in Houston in Cancer Cell.
The median progression-free survival (PFS) did not differ significantly between the near- and far-loop groups (5.6 vs 5.5 months), but the 6- and 12-month rates numerically favored the near-loop group, at 47% versus 30% and 32% versus 20%, respectively.
“This study highlights that exon 20 mutations, particularly insertion mutations, are heterogeneous, and more detailed location information (e.g., helical, near loop, or far loop) may help guide further testing and treatment selection for EGFR exon 20-directed kinase inhibitors,” conclude the researchers.
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