KEY TAKEAWAYS
- This phase 3 study investigated the safety and efficacy of AVA in reducing SOM, specifically in LAHNC pts affecting the oral cavity or oropharynx.
- The study’s primary endpoint was SOM incidence through the end of IMRT. Secondary endpoints were SOM duration through 2 weeks post-IMRT, grade 4 OM incidence through the end of IMRT, and safety.
- AVA significantly improved SOM compared to PBO across various measures, with a safety profile consistent with IMRT/cisplatin expectations.
This phase 3 trial involved patients (pts) who were undergoing intensity-modulated radiotherapy (IMRT) at doses ranging from 60 to 72 Gy (with a minimum of 50 Gy delivered to at least two oral mucositis sites) combined with cisplatin administration either weekly or every three weeks. These pts were randomly assigned in a 3:2 ratio to receive intravenous (IV) avasopasem (AVA) at a dose of 90 mg or a placebo (PBO) Monday through Friday, administered within one hour before each radiation therapy (RT) session. The severity of oral mucositis (OM) was assessed using the WHO scale by trained evaluators at biweekly intervals during RT and then weekly for two weeks following the completion of IMRT.
The study’s primary endpoint was severe oral mucositis (SOM) incidence occurring up to the conclusion of IMRT. Secondary endpoints encompassed the duration of SOM for two weeks following IMRT, the incidence of grade 4 OM up to the end of IMRT, and safety-related outcomes. Additionally, exploratory analyses examined the utilization of opioids and gastronomy tubes.
A total of 455 individuals were enrolled in the study, with 407 (comprising 241 in the AVA group and 166 in the placebo group) forming the primary analysis population. The median age of the participants was 61 years, with 86% male and 82% having tumors in the oropharynx. Notably, the results demonstrated a statistically significant 16% reduction in SOM incidence in the AVA group compared to the PBO group (54% vs. 64%; P=0.045).
Furthermore, there was a substantial 56% relative reduction in the duration of SOM, with a median duration of 8 days in the AVA group compared to 18 days in the placebo group (P=0.002). Grade 4 oral mucositis incidence was also reduced by 27% (P=0.052). Encouragingly, several secondary and exploratory endpoints showed improvement as well. Importantly, the frequencies of adverse events were similar between the treatment groups, with no apparent specific toxicity related to AVA or an increase in cisplatin-related toxicity.
Oncology nurses are crucial in providing primary care to locally advanced head and neck cancer (LAHNC) pts. Nevertheless, there is a scarcity of evidence-based interventions available to mitigate the adverse effects of treatment in this patient population.
The results from this study indicated that AVA yielded both statistically and clinically significant improvements in SOM compared to the PBO. These positive outcomes were consistent across various SOM severity measures, and AVA’s safety profile aligns with the anticipated side effects associated with IMRT and cisplatin treatment. Furthermore, the integration of this intervention into clinical workflows has been successful.
Source: https://ons.confex.com/ons/2023/meetingapp.cgi/Paper/12846
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03689712
Cullen, E., Brown, H., Carringer, J., Amado, A., Pitre, L., Anderson, C. ROMAN: Phase 3 Trial of Avasopasem Manganese (GC4419) for Severe Oral Mucositis (SOM) in Patients Receiving Chemoradiotherapy (CRT) for Locally Advanced Head and Neck Cancer (LAHNC).
