3748 - Long-Term Tumor Outcomes in Patients with Head and Neck Cancer Treated with Avasopasem Manganese to Mitigate Severe Oral Mucositis: A Single Institution Retrospective Analysis

U. Uzomah¹, M. O. Evbuomwan¹, B. Loeffler², and C. M. Anderson¹; ¹Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, IA, ²University of Iowa, Iowa City, IA

Purpose/Objective(s): Avasopasem manganese (AVA), a selective dismutase mimetic, has been tested to mitigate severe oral mucositis in locoregionally advanced head and neck cancer (LAHNC) patients in phase 1b/2a, phase 2b and phase 3 trials. The latter two were multi-national placebo-controlled randomized trials. In this study we aim to analyze long-term tumor outcomes from a single institution top-enroller on those clinical trials. Materials/

Methods: This is an IRB-approved single-center retrospective analysis of patients enrolled in multicenter phase 1b/2a, 2b, and 3 trials for AVA treated with curative chemoradiation therapy (CRT) at our institution between 2014 and 2021. Patients received AVA 30 mg, AVA 90 mg, or placebo. Medical charts were reviewed to extract data on long term tumor outcomes. Locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) probabilities were estimated from the end of CRT and plotted using the Kaplan-Meier method. Cox regression was used to estimate the effect of patient and treatment characteristics on LRRFS, DMFS, PFS, and OS. Estimated effects of predictors were reported as hazard ratios (HR) along with 95% confidence intervals. All statistical testing was two-sided and assessed for significance at the 5% level using SAS v9.4 (SAS Institute, Cary, NC).
Results: Sixty-seven patients were included in this analysis (29 Placebo, 11 AVA 30 mg, 27 AVA 90mg). The median age was 58 years, and 61 (91%) patients were male. The majority of patients were HPV+ (n=51, 79.7%) oropharynx primaries (n=53, 85.5%), who received 70 Gray in 35 fractions (49, 73.1%). There were 3 patients with oral cavity primaries in each treatment arm group. Median follow-up from the end of RT was 4.3 years (range: 0.3 to 8 years). There were 7 (10.4%) local failures, 7 (10.4%) regional failures, 5 (7.5%) distant failures, and 13 (19.4%) deaths. Seven patients (10.4%) developed a second primary malignancy. By treatment arm, there was no statistically significant difference in LRRFS (p=0.23), DMFS (p=0.31), PFS (p=0.24), or OS (p=0.36). Regardless of treatment arm, patients with oral cavity primaries had statistically worse outcomes than those with oropharynx primaries: LRRFS (HR 4.15; p<0.01), DMFS (HR 4.23; p=0.01), PFS (HR 4.18; p<0.01), and OS (HR 4.98; p<0.01).
Conclusion: Our study showed that among patients undergoing CRT for locoregionally advanced head and neck cancer, those who received AVA had similar long-term tumor outcomes compared to patients who received placebo. Regardless of treatment arm, patients with oral cavity primaries had worse outcomes compared to those with oropharyngeal primaries.