Phase III study: AES-14 in patients at risk for mucositis secondary to anthracycline-based chemotherapy

Abstract

8008 Background: Oral mucositis (OM) limits chemotherapy dosing and increases health care costs. AES-14 (Saforis) enhances direct oral mucosal cell uptake of L-glutamine by the Aesgen UpTec system. Prior AES-14 studies in chemotherapy patients suggested safe, effective reduction (20%) of clinically significant OM. Methods: A randomized, double-blind, placebo-controlled crossover multicenter trial was conducted in breast carcinoma patients receiving at least 3 cycles of an anthracycline regimen (AC, CAF or FAC). Patients developing WHO Grade (Gr) 2–4 OM during screening cycle were randomized for crossover in 2 subsequent cycles. Study drug began 1st day of chemotherapy and continued 14 days after last chemotherapy dose or 5 days after OM resolved. Safety was assessed by Adverse Event (AE)/Serious AE evaluations. Primary endpoint analysis compared proportion of patients with ≥ Gr 2 OM while on AES-14 versus placebo. Secondary endpoints included OM duration and OM Assessment Scale outcomes. Results: 2,064 female patients were screened for OM ≥ WHO Gr 2. 326 patients (mean age 51 years) were randomized (15.7% OM rate). Peak OM was primarily WHO Gr 2. No significant randomization imbalances occurred. Comparison of treatment versus placebo outcomes in crossover design requires that no significant drug treatment carryover effect exists. AES-14 administered during 1st treatment cycle reduced ≥ Gr 2 OM incidence in the placebo 2nd treatment cycle (p=0.0269). This carryover effect invalidated crossover efficacy comparison. Primary endpoint analysis thus compared parallel group treatment during 1st cycle only. Incidence of clinically significant OM (WHO Gr 2–4) was 22% less with AES-14 versus placebo (p=0.0261). No AES-14-related SAEs and 2 placebo-associated SAEs were reported. Conclusions: AES-14 reduced incidence of 1st cycle Gr 2–4 OM by 22% in these chemotherapy patients. The significant AES-14 carryover effect suggests that optimizing mucosal repair during one cycle may protect patients from OM during subsequent chemotherapy. Supported by Aesgen Inc. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aesgen Inc. Aesgen Inc.