5527 Background: Oropharyngeal candidiasis (OPC) is the most frequently occurring infection in head and neck cancer (HNC) patients undergoing radiation therapy (RT). Methods: Patients (pts) who had completed RT for HNC at least 6 weeks before entering the study, with OPC confirmed by direct exam or fungal culture were included in 27 French and 9 North African centers. Pts with disseminated candidiasis, having received systemic antifungal agents within less than 14 days were excluded. Group A received the bioadhesive buccal tablet containing 50mg of miconazole (MBBT) qd and group B a buccal gel (MBG) containing 125mg of miconazole q.i.d. for 14 days. A sample size of 103 pts per arm was required to obtain a 90% power to demonstrate non-inferiority of MBBT compared with MBG (α level of 5%, δ of 20%, 2 one sided). Primary endpoint was success at D14, defined as complete (CR) or partial (PR) clinical response. Response was based on the score of oral lesion (0 = none, 1 = single localised, 2 = multiple localised, 3 = extensive or confluent). Response was assessed by the investigator and a blind evaluator. Results: The 282 pts (A=141, B=141) in the modified intent-to-treat (MITT) group included all pts receiving at least one day of treatment and with one efficacy data point. The per-protocol (PP) population was composed of 213 pts with a validated, blinded evaluation of the primary endpoint (A=106, B=107). Null hypothesis that MBBT is inferior to MBG is rejected at the 2.5% level of significance. Conclusions:The efficacy of the Bioadhesive Buccal Tablet (miconazole Lauriad) is achieved with 10 times less (50 mg vs 500 mg) miconazole and on a more convenient schedule (once vs four times per day) than the gel, suggesting the potential for better patient compliance in treating OPC in pts with altered mucosa and xerostomia. Group A miconazole bioadhesive tablet 50 mg qd Group B miconazole gel 125mg q.i.d p value Non-inferiority margin (97.5%) 95% CI MITT CR+PR 70/141 (49.7%) 70/141 (49.7%) 0.0004 11.9% [-11,9%; 11,9%] (282 pts) CR 64/141 (45.4%) 64/141 (45.4%) 0.0004 11.8% [-11.8%; 11.8%] PP (blind evaluation) CR+PR 54/107 (50.5%) 58/106 (54.7%) 0.0112 17.9% [-9,4%; 17.9%] (213 pts) CR 48/107 (44.9%) 53/106 (50%) 0.0152 18.6% [-8.6%; 18.6%] Sensitivity analysis CR+PR 69/137 (50.4%) 69/135 (51.1%) 0.0008 12.8% [-11.3%; 12.8%] (272 pts) CR 63/137 (46%) 63/135 (46.7%) 0.0007 12.6% [-11.4%; 12.6%] Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bio Alliance Bio Alliance