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

Early results from a phase 2 clinical trial, reported in an abstract released today for the IASLC World Conference on Lung Cancer annual meeting later this month, show 23 of 40 patients (58%) 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 clinical trial results so far show poziotinib is likely the first real advance for patients with EGFR and HER2 exon 20 mutations, for whom no available targeted therapies have been effective,” said principal investigator John Heymach, MD, PhD, professor and chair of Thoracic/Head and Neck Medical Oncology.

Heymach will present updated data at the meeting on September 24. Previous early results had been reported for the EGFR patients; the IASLC presentation is the first to include HER2 patients. Researchers estimate exon 20 EGFR mutations occur in about 1% 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 as well.

Response rates of exon 20 patients to other targeted therapies aimed at EGFR and HER2 have been 12% or less, the researchers note:

•Median progression free survival on the EGFR arm of the poziotinib trial was 5.6 months. It has not been reached in the HER2 arm, which opened later.
•Disease control rate—total of complete responses, partial responses, and stable disease—was 90% for the EGFR patients and 83% for the HER2 patients.
•In the EGFR cohort, 60% of patients had a side effect of grade 3 or higher, most commonly skin rash (27.5%), diarrhea (12.5%), and inflammation around the fingernails and toenails called paronychia (7.5%); one patient stopped treatment due to grade 3 skin rash. Side effects in EGFR cohort were similar. One death from pneumonitis in the HER2 cohort was considered to be possibly drug-related.