New findings from a phase III clinical trial presented at the American Society of Clinical Oncology (ASCO) point to Pfizer’s dacomitinib as a potential new treatment for patients newly diagnosed with advanced, epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer (NSCLC).
Lung cancer is the leading cause of cancer-related death among men and women in the U.S., according to the National Cancer Institute. An estimated 200,000 new cases of the disease are diagnosed each year. NSCLC is more common than small cell lung cancer.
Currently, EGFR tyrosine kinase inhibitors (TKI) are the standard treatment for the disease. The phase III study is the first phase III head-to-head comparison of two EGFR TKIs—gefitinib, approved for NSCLC in May 2003 (Iressa from AstraZeneca), and dacomitinib, an investigational agent yet to be approved. Compared to gefitinib, the data showed dacomitinib delayed cancer growth by a median of 5.5 months more.
Study findings
In the phase III clinical trial, researchers randomly assigned 452 patients from Asia and Europe who were newly diagnosed with IIIB or IV, EGFR-positive NSCLC to receive dacomitinib or gefitinib.
Patients who received dacomitinib had a 41 percent lower chance of cancer progression or death than those who received gefitinib. The progression-free survival was 14.7 months with dacomitinib, compared to 9.2 months with gefitinib.
Longer follow up is needed to assess the median overall survival.
While dacomitinib was shown to block EGFR more effectively than first-generation inhibitors, it also leads to stronger suppression of the normal EGFRs in healthy tissues, causing more side effects such as skin rash, acne, and diarrhea.
“We changed the treatment paradigm for EGFR-positive lung cancer a few years ago when targeted therapy replaced chemotherapy,” said lead study author Tony Mok, M.D., a professor and chair of the Department of Clinical Oncology at the Chinese University of Hong Kong in Hong Kong, China in a release from ASCO. “This study shows that dacomitinib may be an even more effective treatment for these patients. However, patients should be aware of the need to deal with potential side effects when making treatment decisions.”
Side effects
During the trial, the dose of the drug was lowered in about 60 percent of patients due to side effects. Specifically, 14 percent of patients experienced acne and eight percent of patients experienced diarrhea. By comparison, eight percent of patients taking gefitinib experienced liver enzyme abnormalities–the most common severe side effect of that drug in this trial.
“Dacomitinib is a more potent, second-generation EGFR inhibitor that shares the issue of increased side effects in the skin and gastrointestinal tract, like another second-generation EGFR inhibitor, afatinib (Gilotrif). In spite of this, the activity seen in this study should allow for consideration of this effective therapy in this patient population,” said Mok.
ASCO experts from the meeting seem to agree.
“It’s been nearly 15 years since EGFR-targeted therapies were introduced, helping extend survival for thousands of patients in the time since. The second generation of these therapies is more effective, but can also cause greater side effects, so patients and their doctors will need to weigh the risks and benefits,” said ASCO Expert John Heymach, M.D., Ph.D. in a press release.
Dacomitinib is not yet approved for any indication.
Pfizer and SFJ Pharmaceuticals Group have a collaborative development agreement to conduct ARCHER 1050 across multiple sites.
Filed Under: Drug Discovery
