A drug revived by researchers at The University of Texas MD Anderson Cancer Center continues to provide unprecedented response rates among stage 4 non-small cell lung cancer patients with genetic mutations that have previously defied treatment.

Early results from a phase 2 clinical trial, reported today at the IASLC 19th World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer, show 24 of 44 patients (55%) with exon 20 mutations in the epidermal growth factor receptor (EGFR) and 6 of 12 patients (50%) with exon 20 mutations in the human epidermal growth factor receptor (HER2) had their tumors shrink at 8 weeks after treatment with poziotinib.

“These findings confirm earlier observations that poziotinib is highly active against this previously untargetable mutation and durable responses are observed, with some patients on treatment now for more than a year,” said principal investigator John Heymach, MD, PhD, professor and chair of thoracic/head and neck medical oncology.

Nineteen patients remain on treatment, six for more than a year. All responses so far are partial responses.

Previous early results had been reported for 11 EGFR patients. Heymach’s presentation is the first to include HER2 patients. Researchers estimate exon 20 EGFR mutations occur in about 1%-2% of non-small cell lung cancer patients and HER2 exon 20 variations occur in about 3%.

The MD Anderson investigator-initiated clinical trial provides the largest dataset among exon 20 lung cancer patients worldwide. Spectrum Pharmaceuticals, which makes poziotinib, has opened a multicenter phase 2 trial.

Response rates of exon 20 patients to other targeted therapies aimed at EGFR and HER2 have been 12% or less, the researchers note. There are no approved therapies for these patients.

•Median progression-free survival on the EGFR arm of the poziotinib trial was 5.5 months. It has not been reached in the HER2 arm.
•In the EGFR cohort, 56% of patients had a side effect of grade 3 or higher, most commonly skin rash (34.9%), diarrhea (17.5%), and inflammation around the fingernails and toenails called paronychia (9.5%); one patient stopped treatment due to grade 3 skin rash and 60% had dose reductions. Side effects in HER2 cohort were similar. One death from pneumonitis in the HER2 cohort was considered to be possibly drug-related.

—Newswise