BOSTON—A gene therapy agent that delivers a normal p53 gene to the tumor significantly increased survival by 4.5 months in end-stage head and neck cancer patients with p53-favorable tumor profiles, compared to those with unfavorable profiles.
Principal investigator John Nemunaitis, MD, medical director, Mary Crowley Medical Research Center at Baylor-Sammons Cancer Center, Dallas, reported the results of the phase III, open-label, multicenter, randomized trial at the American Society of Gene Therapy annual meeting.
The p53 tumor suppressor therapy (Advexin from Introgen Therapeutics, Inc. Austin, Texas) is designed to restore abnormal p53 tumor suppressor function, which is associated with cancer initiation, progression, and treatment resistance.
The trial showed that p53 expression in the patient’s tumor before treatment is a reliable biomarker for selecting patients for the new gene therapy. A p53 favorable profile was defined as high or low normal p53 levels or low mutant p53 levels; an unfavorable profile was defined as high mutant p53 levels.
The trial included 123 patients with recurrent squamous cell carcinoma of the head and neck whose cancers were refractory to platinum or taxane chemotherapy.
Among the population with biomarker analysis (n = 67), survival was significantly increased with Advexin in the p53 favorable group, compared with the p53 unfavorable group (7.2 months vs 2.7 months, P < .0001). In contrast, methotrexate-treated patients with a p53 profile favorable for Advexin treatment had a median survival of only 4.3 months whereas those with the unfavorable Advexin profile had a median survival of 5.9 months (see Table).
There was no significant difference in survival between Advexin- and methotrexate-treated patients in the intent-to-treat population, which included both p53 favorable and unfavorable patients in both study arms, but Advexin had a superior safety profile.
Advexin’s side effects were primarily self-limiting (fever, chills, and injection site discomfort or pain). Common side effects with methotrexate included lymphopenia (26% vs 5% with Advexin), stomatitis (13% vs 0%), leukopenia (12% vs 0%), neutropenia (12% vs 3%), and pneumonia (11% vs 2%). “If approved, this product would provide significant medical benefit to these seriously ill patients who have failed other treatments,” Dr. Nemunaitis said.