Dacomitinib Fails in Pretreated Non-small Cell Lung Cancer

Zosia Chustecka

January 27, 2014

The investigational agent dacomitinib (under development by Pfizer) has failed in 2 phase 3 trials in patients with pretreated non-small cell lung cancer (NSCLC), although a third trial is ongoing in treatment-naïve NSCLC patients. The company announced top-line results in a press release issued today and says that full results will be reported at upcoming meetings.

Dacomitinib offers a new mechanism of action, and is described as a pan-HER (pan-human epidermal growth-factor receptor [EGFR]) kinase inhibitor, blocking the activity of HER1/EGFR, HER2, and HER4. This is a wider range of inhibition than seen with the EGFR inhibitors that are already on the market, such as erlotinib (Tarceva) and gefitinib (Iressa), with which it was being compared in some of the trials.

However, the new drug failed to show superiority.

In one of the failed trials, known as ARCHER 1009, dacomitinib was compared with erlotinib when used as second- or third-line therapy in NSCLC patients who had previously been treated with chemotherapy, all of whom had KRAS wild-type NSCLC. Dacomitinib failed to meets its objective of demonstrating statistically significant improvement in progression-free survival when compared with erlotinib.

The second failed trial, known as the NCIC CTG BR.26 trial and conducted by the Canadian Cancer Society, involved patients with advanced NSCLC who had progressed after both chemotherapy and an EGFR inhibitor. Dacomitinib did not meet its objective of prolonging overall survival versus placebo.

"While we are disappointed in the results, lung cancer is a complex disease, and the use of targeted agents to treat specific patient populations continues to evolve," said Mace Rothenberg, MD, senior vice president of clinical development and medical affairs and chief medical officer for Pfizer Oncology. The data will now be analyzed for patients with specific molecular mutations, he added.

Third Trial Continuing

A third phase 3 trial, known as ARCHER 1050, is continuing. This study is comparing dacomitinib versus gefitinib in treatment-naïve patients with EGFR-mutant advanced NSCLC, with a progression-free survival end point. The study is being conducted in Asia and Europe, and results are expected in 2015.

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