IASLC 2017: Poziotinib Yields High Response Rates in Patients With NSCLC With EGFR Exon 20 Insertion
A targeted therapy studied at The University of Texas MD Anderson Cancer Center has produced high response rates among patients with metastatic non–small cell lung cancer (NSCLC) that carries a highly treatment-resistant mutation. Preliminary results were presented at the International Association for the Study of Lung Cancer (IASLC) 18th World Conference on Lung Cancer (WCLC) in Yokohama, Japan.
Study Findings
In a phase II clinical trial, the novel agent poziotinib, an oral, quinazoline-based pan-HER inhibitor, shrank tumors by at least 30% in 8 (73%) of 11 patients with NSCLC whose cancer included an epidermal growth factor receptor (EGFR) exon 20 insertion mutation. Shrinkage ranged from 30% to 50% among the 8 patients achieving a partial response. One patient has had disease progression on the trial, which began in March. All patients experienced some tumor shrinkage.
About 2% of NSCLC patients have an EGFR exon 20 insertion. The trial has enrolled 27 patients and is expected to enroll up to 50. Other tyrosine kinase inhibitors against EGFR have been approved by the U.S. Food and Drug Administration, but none have proved effective against the exon 20 insertion.
Of the 11 patients, 6 have had their dose reduced due to side effects, mainly due to rash, but also diarrhea, mucositis, and paronychia.
“We’ve had no effective drugs for these patients, who historically have a progression-free survival of about 2 months and a response rate of less than 20% for other therapies,” said clinical trial leader John Heymach, MD, PhD, Chair of Thoracic/Head and Neck Medical Oncology and the David Bruton Junior Chair in Cancer Research at MD Anderson.
“These early results are highly encouraging, and our research shows that poziotinib’s structure makes it a great potential fit for attacking this mutation,” Dr. Heymach said.
The investigator-initiated clinical trial marks the latest progress in the identification and development of poziotinib for this group of patients conducted by MD Anderson’s Lung Cancer Moon Shot, which is co-led by Dr. Heymach as part of the institution’s Moon Shots Program. The program was launched in 2012 to accelerate the development of new approaches to cancer based on scientific discoveries.
Preclinical Research
Poziotinib had been tried and abandoned as a general EGFR inhibitor against lung cancer when Dr. Heymach’s team turned up evidence of its potential against the exon 20 mutation through a drug screening program that is part of the MD Anderson Lung Cancer Moon Shot.
Postdoctoral fellow Jacqulyne Robichaux, PhD, tapped the Genomic Marker–Guided Therapy Initiative (GEMINI), which includes tumor samples and detailed clinical information on more than 4,000 lung cancer patients treated at MD Anderson since 2012. Dr. Robichaux developed EGFR exon 20 NSCLC cell lines as well as patient-derived xenograft models and tested a variety of EGFR inhibitors against them under the Lung Cancer Moon Shot’s drug repurposing program.
“Poziotinib is the only drug we’ve ever found that was dramatically better for exon 20 than it was for the classical EGFR mutation, T790M, which everyone tests,” Dr. Heymach said.
The multidisciplinary team then identified structural aspects of the drug that explain the divergent impact. Dr. Heymach and colleagues contacted Spectrum Pharmaceuticals, a Nevada-based biotechnology company that initially developed poziotinib. Subsequent collaboration included compassionate use of poziotinib for some patients with advanced disease and rapid development of the phase II clinical trial.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
