An HSP90 Inhibitor for EGFR-Mutant Lung Cancer

Patients with epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) who are treated with frontline EGFR tyrosine kinase inhibitors often have excellent disease control, typically for 9 to 14 months. When disease progression occurs, it usually stems from acquired T790M EGFR resistance mutation.

In preclinical models of EGFR-mutant NSCLC, the HSP90 inhibitor AUY922 was shown to induce apoptosis. To further test the use of AUY922 in this setting, investigators performed a phase I/II trial of AUY922 plus erlotinib in 37 patients with EGFR-mutated disease who developed acquired resistance after 6 months of erlotinib therapy.

In the phase I portion of the trial, involving 18 patients, the maximum tolerated dose (MTD) wa…