Jun 5 2017
"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, MD, PhD.
Findings from a phase III clinical trial point to a potential new treatment for patients newly diagnosed with advanced, epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer (NSCLC). Compared to the EGFR inhibitor gefitinib (Iressa), one of the standard targeted medicines for this disease, second-generation EGFR inhibitor dacomitinib delayed cancer growth by a median of 5.5 months more.
The study will be featured in a press briefing today and presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting.
Each year, about 140,000 people worldwide (15,000 in the United States alone) are diagnosed with EGFR-positive NSCLC. EGFR-positive cancers have genetic changes that lead to an overactive EGFR protein, which fuels the growth of cancer cells. EGFR tyrosine kinase inhibitors (TKI) are the standard treatment for people with newly diagnosed EGFR-positive NSCLC. This study is the first phase III head-to-head comparison of two EGFR TKIs.
"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, MD, a professor and chair of the Department of Clinical Oncology at the Chinese University of Hong Kong in Hong Kong, China. "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."
Due to its chemical properties, dacomitinib blocks EGFR more effectively than first-generation inhibitors, such as gefinitib and erlotinib, and this explains its ability to keep tumor growth in check longer. On the other hand, this also leads to stronger suppression of the normal EGFRs in healthy tissues, causing more side effects such as skin rash, acne, and diarrhea.
About the Study
In this phase III clinical trial, researchers randomly assigned 452 patients newly diagnosed with IIIB or IV, EGFR-positive NSCLC to receive dacomitinib or gefitinib. The patients were enrolled in Asia and Europe.
Patients who received dacomitinib had a 41% 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.
The most common severe (grade 3) side effects of dacomitinib were acne (in 14% of patients) and diarrhea (in 8% of patients). The dose of daconitinib was lowered in about 60% of patients due to side effects. Liver enzyme abnormalities were the most common severe (grade 3) side effect of gefitinib (in 8% of patients).
"Dacomitinib is a more potent, second-generation EGFR inhibitor that shares the issue of increased side effects in the skin and gastrointestinal tract, like 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 Dr. Mok. Another second-generation EGFR inhibitor, afatinib, is already FDA approved as an initial treatment for EGFR-positive NSCLC. Dacomitinib is not yet approved for any indication.