Two-Year Tumor Outcomes of a Phase 2B, Randomized, Double-Blind Trial of Avasopasem Manganese (GC4419) Versus Placebo to Reduce Severe Oral Mucositis Owing to Concurrent Radiation Therapy and Cisplatin for Head and Neck Cancer.

Carryn M Anderson, Christopher M Lee, Deborah Saunders, Amarinthia E Curtis, Neal E Dunlap, Chaitali Nangia, Arielle S Lee, Philip Kovoor, Voichita Bar-Ad, Abhinand V Pedadda, Jon Holmlund, Matt Downs, Stephen T Sonis

Journal: International journal of radiation oncology, biology, physics 2022;114(3):416-421

PMID: 35724774

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Abstract

PURPOSE

Avasopasem manganese (GC4419), an investigational selective dismutase mimetic radioprotector, reduced duration, incidence, and severity of severe oral mucositis (World Health Organization grade 3-4) in a phase 2b, randomized, double-blind trial of patients receiving concurrent cisplatin (cis) and radiation therapy (RT) for head and neck cancer. We report the secondary endpoints of final 1- and 2-year tumor outcomes and exploratory data on trismus and xerostomia.

METHODS AND MATERIALS

Patients with locally advanced oral cavity or oropharynx cancer to be treated with definitive or postop cis and RT were randomized to 1 of 3 arms: 30 mg avasopasem, 90 mg avasopasem, or placebo. Pairwise comparisons of Kaplan-Meier estimates (each active arm separately vs placebo) were made for overall survival, progression-free survival, locoregional control, and distant metastasis-free survival. Xerostomia and trismus data were collected at each follow-up visit and analyzed for trends by post-RT timepoint and treatment group.

RESULTS

At a median follow-up for the entire cohort of 25.5 months (25th-75th percentile, 24.6-26.2 months; range, 0.2-31.9 months), Kaplan-Meier estimates of 1- and 2-year overall survival, progression-free survival, locoregional control, and distant metastasis-free survival were not statistically different. No trends were apparent in xerostomia or trismus data.

CONCLUSIONS

Avasopasem does not lead to statistically different tumor control outcomes when used concurrently with cis and RT for head and neck cancer. There was no detectable effect on trismus or xerostomia.

Address: Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa. Electronic address: [email protected].; Radiation Oncology, Cancer Care Northwest, Spokane, Washington.; Dental Oncology, Northeast Cancer Center/Health Sciences North, Sudbury, Ontario, Canada.; Radiation Oncology, Spartanburg Medical Center, Spartanburg, South Carolina.; Radiation Oncology, University of Louisville/James Graham Brown Cancer Center, Louisville, Kentucky.; Hematology/Oncology University of California, Irvine Medical Center, Orange, California.; Hematology/Oncology University of Texas Health Science Center at Tyler/HOPE Cancer Center, Tyler, Texas.; Oncology, Texas Oncology, Plano West, Plano, Texas.; Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania.; Radiation Oncology, Renown Regional Medical Center, Reno, Nevada.; Clinical Development, Galera Therapeutics, Inc, Malvern, Pennsylvania.; Biostatistics, Statistics Collaborative, Inc, Washington, DC.; Clinical Development, Primary Endpoint Solutions, Waltham, Massachusetts.

DOI: 10.1016/j.ijrobp.2022.06.063