A small molecule can provide a “clinically meaningful reduction” in severe oral mucositis without affecting tumor control in head and neck cancer, according to an investigator from a phase 2 trial.
The molecule, GC4419 (avasopasem manganese), is designed to convert superoxide to hydrogen peroxide and oxygen, thereby protecting normal tissue from damage associated with radiotherapy.
Investigators tested GC4419 in a phase 2 trial of patients with locally advanced oral cavity or oropharynx cancer who received intensity-modulated radiotherapy plus cisplatin. Initial results from this trial were published in December ().
of University of Iowa Hospitals & Clinics in Iowa City, at the Multidisciplinary Head and Neck Cancer Symposium, sponsored by the American Society for Radiation Oncology.
The trial () enrolled 223 patients scheduled to be treated with intensity-modulated radiotherapy (60-72 Gy or greater than 50 Gy to more than two oral sites) plus cisplatin (weekly or every 3 weeks).
The patients were randomized to receive 30 mg of GC4419 (n = 73), 90 mg of GC4419 (n = 76), or placebo (n = 74) intravenously over 60 minutes prior to each radiotherapy fraction. Baseline patient and tumor characteristics were well balanced among the treatment arms.
Efficacy and safety
The study’s primary endpoint was the duration of severe oral mucositis. When compared with placebo, the 90-mg dose of GC4419 conferred a 92% reduction in median days of severe oral mucositis (P = .024).
The 90-mg dose of GC4419 also reduced the incidence of severe oral mucositis by 34% (P = .009) and the rate of grade 4 oral mucositis by 47% (P = .045) when compared with placebo.
“GC4419, particularly the 90-mg dosage, provides a clinically meaningful reduction in severe oral mucositis duration, incidence, and severity,” Dr. Anderson noted.
“Safety was comparable across study arms,” she added. “The most frequent adverse events were those already expected with cisplatin and radiation, and those were not worsened in any way by the addition of this drug.”
Adverse events expected with GC4419 were “mild and transient,” according to Dr. Anderson. These events included syncope, hypotension/orthostasis, and oral/facial paresthesia.
Grade 3 syncope occurred in 4% of patients in the placebo arm, 4% in the 30-mg arm, and 6% in the 90-mg arm. Grade 3 hypotension/orthostasis occurred in 6%, 4%, and 4%, respectively. Grade 1 oral/facial paresthesia occurred in 15%, 10%, and 19%, respectively.
“The 1- and 2-year tumor control is similar with utilization of [GC4419], and this is consistent with the drug’s known mechanism and previous animal models,” Dr. Anderson said.
At 1 and 2 years, there were no significant differences between the treatment arms with regard to locoregional control, distant metastasis, progression-free survival, or overall survival.
The 1-year progression-free survival was 82% in the placebo arm, 86% in the 30-mg arm, and 80% in the 90-mg arm. The 1-year overall survival was 93%, 91%, and 88%, respectively.
The 2-year progression-free survival was 77% in the placebo arm, 76% in the 30-mg arm, and 77% in the 90-mg arm. The 1-year overall survival was 87%, 85%, and 86%, respectively.