Dacomitinib after erlotinib failure: modest effects in non-small cell lung cancer

This study aimed to assess use of dacomitinib in patients with advanced non-small cell lung cancer (NSCLC) who had previously failed to respond to chemotherapy and erlotinib (Tarceva).

NSCLC is the most common type of lung cancer. Erlotinib and gefitinib (Iressa) are used to treat NSCLC. They specifically target  one member of the epidermal growth factor receptors (EGFR; proteins that are important in signalling within cells): EGFR/HER1.

EGFR proteins are mutated (permanently changed) in cancer cells in some patients with NSCLC, making them very suitable for treatment with erlotinib and gefitinib. However, many NSCLC patients may have mutations in other HERs (HER2, HER3, HER4). In such patients, treatment with erlotinib, gefitinib and chemotherapy is often met with failure. Dacomitinib, an experimental drug, has shown promise in NSCLC patients with such mutations.

This study aimed to assess the safety, effectiveness and effect on health-related quality-of-life of dacomitinib. 66 patients were enrolled in this study; 50 had cancer in glandular cells of lungs (adenocarcinoma) and 16 had non-adenocarcinoma. Patients had one of a variety of EGFR mutations or no EGFR mutation. Patients had progressed despite treatment with erlotinib (or some form of EGFR-targeting therapy) and 1 or 2 lines of chemotherapy. Patients received 45 mg of dacomitinib once daily on an empty stomach. 

4.8% of patients with adenocarcinoma had a partial response, while 6.3% of those with non-adenocarcinoma cancer had a partial response. Partial response refers to a decrease in the size of the tumor. 36 patients experienced stable disease (cancer did not get worse or get better), of whom 28% saw a benefit for greater than 6 months. 

The time from treatment until disease progression for those with adenocarcinoma was 12 weeks compared to 11 weeks for those with non-adenocarcinoma. Those with EGFR mutated tumors on average had 18 weeks until disease progression. 

The average overall survival was 45 weeks in patients with adenocarcinoma and 27 weeks in patients with non-adenocarcinoma. Again, patients with EGFR mutated tumors had a longer overall survival (57 weeks). For EGFR mutated tumors, the rate of survival was 59% at 12 months. 

The majority of treatment-related side effects were mild to moderate in severity and included diarrhea (85%), inflammation of skin (68%), dry skin (38%) and fatigue (38%).

The authors concluded that dacomitinib showed preliminary benefit in NSCLC with EGFR/HER mutations with tolerable adverse effect and may be effective in certain genetic populations. 

The primary end point i.e. complete disappearance of detectable tumor was not achieved in this trial.