Stephen Liu, Chief, Division of Hematology and Oncology at Georgetown Lombardi Comprehensive Cancer Center, shared on X:
“Early insights into resistance to HER2 TKIs in NSCLC emerged at WCLC26. Zongertinib and sevabertinib now both approved as 1L+ treatment for advanced NSCLC with a HER2 TKD mt. While efficacy similar, these are distinct agents and we need to learn how to leverage those differences.
In Beamion LUNG-1 with zongertinib, 8 paired tissue results from pts with PD showed two acquired HER2 mutations: T862A and S783C. Notably absent were T798I (gatekeeper) and C805S (binding site). The acquired mutations not detected in plasma.
In SOHO-01 with sevabertinib, much larger dataset from Xiuning Le, Arsela Prelaj. In 73 pts with paired evaluable ctDNA (HER2+ at baseline), 22 had a putative resistance event. T862A seen in 16% with one compound T798I/T862A. HER2 amplification seen in 3%. No C805S and no S783C.”
To which Luis Raez, Director of the Thoracic Oncology Program at Memorial Healthcare System, added:
“We can find this if we always do NGS after treatment failure in plasma and tissue, in this case liquid bx did not get the resistance but in many other genetic aberrations is good to find it.”
This also can be interesting:
