A top Pfizer drug flops in two PhIII lung cancer studies

Pfizer CEO Ian Read

One of Pfizer's ($PFE) top cancer drug prospects in the late-stage pipeline failed the first two Phase III studies for non-small cell lung cancer, presenting the pharma giant with a key setback for its oncology group. 

Investigators say that dacomitinib--held up by CEO Ian Read as one of the company's most promising experimental therapies--failed to demonstrate an improved rate of progression-free survival compared to a group receiving Tarceva. The second trial failed to produce a significant improvement in overall survival. The non-small cell lung cancer patients had previously failed other standard therapies for the disease. Pfizer announced only top-line results today, holding on to the data for a later scientific meeting.

Pfizer has a ways to go, though, before deciding the final fate of the drug. There's a third Phase III trial underway that compares dacomitinib against Iressa. And the company plans to delve into the late-stage data to see if any subgroups responded better than others, possibly pointing to a new way forward to salvage the therapy. But it's an ominous turn that raises severe doubts about the drug's future.

Dacomitinib is described as an irreversible pan-HER kinase inhibitor, which blocks the kinase activity of HER1/EGFR, HER2, and HER4 by binding to the receptor tyrosine kinase domains and preventing "autophosphorylation," preventing tumor growth and promoting apoptosis, or cancer cell death.

Pfizer underwent a jarring R&D reorganization in recent years, chopping billions of dollars out of its research budget and narrowing its focus. Cancer remained a top category, though, with drug like palbociclib and dacomitinib heralded as two of the company's most promising programs. While Pfizer scored a slate of new drug approvals in 2012, the company has experienced some severe headwinds on marketing drugs like Eliquis and Xeljanz. 

The news today is also likely to send a chill through SFJ Pharmaceuticals, which struck a deal with Pfizer to run and finance a late-stage program for dacomitinib in Asia.

"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, the chief medical officer for Pfizer Oncology, in a statement. "We are analyzing the findings from both ARCHER 1009 and BR.26 to better understand the effects of dacomitinib in molecularly defined subgroups of patients with advanced NSCLC, including those with EGFR mutations."

- here's the release