Patients with a greater than 10 pack/year history of smoking tend to develop an especially dangerous form of head and neck squamous cell cancer (HNSCC) for which prognosis remains poor and treatments have changed little during the past two decades. However, recent phase 1 clinical trial results by the Head and Neck Cancer Group at University of Colorado Cancer Center suggest a possible new direction for these patients. The first-in-human trial of the oral PARP inhibitor olaparib, with the anti-EGFR drug cetuximab and radiation, led to 72 percent 2-year survival in 16 patients on trial, compared with an expected 2-year survival rate of about 55 percent for standard-of-care treatment.
“Colorado promotes innovation, and this trial was certainly innovative when it was designed by our group,” says David Raben, MD, CU Cancer Center investigator and professor in the CU School of Medicine Department of Radiation Oncology. “Much credit goes to Antonio Jimeno, MD, PhD who was very supportive of this idea and helped move this forward along with Dr. Sana Karam and Dr. Daniel Bowles.”
The drug cetuximab targets EGF receptor signaling (EGFR) and while it earned FDA approval in 2006 for use against head and neck cancers over-expressing EGFR, Raben stated there is significant room for improvement.
“That’s where olaparib and radiation come in,” he says. “Ten years ago, I was on a sabbatical from CU, working for AstraZeneca in England. And I remember taking the train from Manchester to Cambridge to learn about this new drug from a small biotech company called Kudos Pharmaceuticals. It was a PARP-inhibitor, meant to keep cells from repairing damaged DNA. That’s the drug we now call olaparib.”