146 - Opioid Therapy vs. Multimodal Analgesia in Head and Neck Cancer (OPTIMAL-HN): Results of a Randomized Clinical Trial

S. Zayed¹, P. Lang¹, N. E. Read¹, R. J. M. Correa¹, A. Mutsaers¹, C. D. Goodman¹, K. D’Angelo¹, K. Kieraszewicz¹, D. Vanwynsberghe¹, A. Kingsbury-Paul¹, K. Crewdson¹, C. Carreau², E. Winquist², S. Kuruvilla², P. Stewart², D. Moulin³, A. Warner¹, and D. A. Palma¹; ¹Department of Radiation Oncology, Western University, London Health Sciences Centre, London, ON, Canada, ²Department of Medical Oncology, Western University, London Health Sciences Centre, London, ON, Canada, ³Departments of Clinical Neurological Sciences and Oncology, Western University, London Health Sciences Centre, London, ON, Canada

Purpose/Objective(s): Radiation-induced mucositis (RIM) pain confers substantial morbidity for head and neck cancer (HNC) patients undergoing radiotherapy (RT) or chemoradiotherapy (CRT). With no established standard treatment, OPTIMAL-HN aimed to demonstrate the non-inferiority of multimodal analgesia (MMA; analgesic medications with different mechanisms of action) to the institutional standard of opioid analgesia alone. Materials/

Methods: OPTIMAL-HN (NCT04221165) was an open label, single-institution, non-inferiority, randomized clinical trial. HNC patients receiving curative-intent RT/CRT and experiencing moderate 4/10 RIM pain were randomized 1:1, stratified by RT vs. CRT, to opioids alone per institutional standard or MMA (Pregabalin, Acetaminophen, Naproxen, and opioids if required). The primary endpoint was mean pain score (range: 0-10) during the last week of RT. Secondary endpoints included mean weekly opioid use, duration of opioid requirement, mean daily pain score, quality of life, hospitalizations for analgesic medication-related complications, time to feeding tube insertion, weight loss, toxicity, RT interruptions, and death. Assuming a non-inferiority margin of 1 point, a standard deviation of 1.5 in both arms (80% power, 1-sided alpha 0.05, dropout rate 6%), 62 patients were required. All analyses were pre-specified, including testing for superiority if non-inferiority was demonstrated, and intention-to-treat.
Results: Forty-nine patients were enrolled, 25 in the opioid analgesia alone arm and 24 in the MMA arm. The trial was prematurely closed due to slow accrual. Baseline characteristics were well-balanced between arms; median age was 61 (IQR: 53-70) years; 36 male (73.5%) and 13 female (26.5%); baseline median pain score was 5 (IQR: 4-6) in the opioid arm and 4 (IQR: 4-6) in the MMA arm (p=0.161). Median follow-up was 4.24 (IQR: 3.75-4.73) months. The primary endpoint, mean pain score during the last 7 days of RT, was 5.10 (95% CI: 4.11-6.09) in the opioid arm and 4.85 (95% CI: 3.81-5.90) in the MMA arm (non-inferiority p=0.039, superiority p=0.724). Analyzing all pain scores from enrollment to 6 weeks post-RT using linear mixed models, MMA demonstrated significantly lower pain scores compared to opioids alone (non-inferiority p=0.002, superiority p<0.001). Median weekly opioid use was numerically higher in the opioid arm (99.2 mg oral morphine equivalent dose [OMED], IQR: 16.3-173.1) compared to the MMA arm (50.5 mg OMED; IQR: 8.4-126.3), although nonsignificant (p=0.435). One patient in the MMA arm was admitted with grade 3 acute kidney injury, possibly related to the analgesic regimen. There was no grade = 3 toxicity in the opioid arm. Arms were similar for all other secondary endpoints.
Conclusion: MMA demonstrates non-inferiority to opioid analgesia alone in managing RIM pain during the last week of RT and superiority when analyzing the post-RT time period. MMA is therefore an effective analgesic regimen and should be considered for use in HNC patients.