Two-Year Intention-to-Treat Analysis for Tumor Outcome in Patients Treated with Avasopasem for Oral Cavity and Oral Pharynx Primaries

Purpose/Objective(s) IMRT plus cisplatin (CRT) is established treatment for LAHNC, but ∼70% of patients develop severe oral mucositis (SOM), often requiring feeding tube nutrition. Avasopasem (AVA) is an investigational small molecule selective dismutase mimetic converting superoxide to hydrogen peroxide, which may protect normal cells from, and potentially sensitize cancer cells to, RT (Anderson 2019, Sishc 2021). In a randomized, double-blind phase 3 trial, AVA substantially reduced duration and incidence of SOM versus placebo (PBO) without an adverse effect on safety or 1-yr survival (Anderson 2022). Present analysis assesses intention-to-treat (ITT) 1-yr tumor outcomes and 2-yr survival. Materials/Methods Patients with oral cavity (OC) or oropharynx (OP) LAHNC receiving 60-72 Gy of IMRT (≥50 Gy to ≥2 OM sites) plus cisplatin (weekly or q3 weeks) randomized 3:2 to IV AVA 90 mg vs PBO before each RT fraction. Tumor outcomes (LRC, PFS & DDC) were followed 1 year and overall survival (OS) 2 years, both for ITT and key sub-populations: Overall Tumor Stage; OC vs OP; HPV- vs HPV+; Definitive vs Post-op; QW vs Q3W cisplatin. Results were also compared to prior trial and recent literature. Results 455 patients were randomized, but 20 never received AVA or PBO, and 28 were excluded because of administrative suspension of dosing, leaving ITT safety/efficacy population of 407. Two-year OS was similar for AVA and PBO, 89% (95% CI: 84-93) vs 93% (95% CI: 88-96), respectively. Patients had similar one-year LRC (94% AVA vs 98% PBO), PFS (95% vs 98%), and DDC (96% vs 97%). Nine excess deaths occurred in AVA arm with clustering of 4 at 1 enrollment site. Four non-oncologic deaths occurred during CRT with disparate causes, and 4 excess deaths occurred late, 18 -21 months from randomization (1 progressive disease, 1 second cancer, 2 unknown). In HPV+ low-risk patients (n = 327) both arms had comparable or superior OS (AVA = 93%, PBO = 98%) to similar populations treated on RTOG 1016 (2y OS 90%) and the AVA phase 2b GT-201 study (93%). No antagonism of AVA on tumor control was evident in patients with high-risk disease: 2-year OS in patients with AJCC stage III/IVA/IVB (n=146) was 84% AVA vs 83% PBO, OC tumor site (n=59) was 76% vs 81%, and HPV negative (n=71) was 74% vs 74%, respectively. 80% of patients were treated definitively with CRT, with no detriment on 2-yr overall survival in this subgroup (92% AVA vs 95% PBO). There was no difference in OS based on cisplatin dosing schedule (QW 89% vs 93%, Q3W 90% vs 93%). Conclusion Based on 2-year ITT analysis, AVA does not seem to have oncologic detriment in both low and high-risk patients compared to PBO. Both arms performed better than previously published data for a mixed OC/OP, HPV+/HPV- population.