Journal article
Benefit of Avasopasem Manganese on Severe Oral Mucositis in Head and Neck Cancer in the ROMAN Trial: Unplanned Secondary Analysis
Advances in radiation oncology, Vol.10(1), 101674
01/2025
DOI: 10.1016/j.adro.2024.101674
PMCID: PMC11638593
PMID: 39678920
Abstract
Oral mucositis is a debilitating side effect of cisplatin and intensity-modulated radiation therapy (IMRT) in patients with head and neck cancer. The phase 3 ROMAN trial showed avasopasem manganese (AVA) significantly decreased individual endpoints of incidence and duration of severe oral mucositis (SOM, World Health Organization [WHO] grade 3-4), with nominal decrease in severity (WHO grade 4) and significant increase in the delay in onset of SOM. We sought to determine the Net Treatment Benefit (NTB) of AVA versus placebo (PBO) using the generalized pairwise comparisons (GPC) method.
GPC is a statistical method that permits simultaneous analysis of several prioritized outcomes, comparing all possible pairs of a patient in the active (i.e., AVA) group and a patient from the control (i.e., PBO) group. NTB is the net benefit across all the outcomes for AVA compared to PBO. Key clinically relevant outcomes from ROMAN were prioritized: 1) WHO grade 4 OM incidence, 2) SOM incidence, 3) days of SOM, 4) days to SOM onset, with 7 days difference defined as the clinical relevance threshold for SOM days and SOM onset.
GPC analysis of 407 patients (AVA = 241, Placebo = 166) stratified by cisplatin schedule and treatment setting resulted in 13,969 pairwise comparisons. AVA showed statistically significant net benefit on all four key outcomes with a 53.9% probability that AVA would benefit patients versus a 35.0% probability that PBO would; the difference between these probabilities was a NTB of 18.9% (p=0.0012), translating to an AVA number needed to treat of 5.3 patients. All outcomes contributed to NTB, reflecting improvements in SOM incidence, onset and duration, and in Grade 4 OM incidence seen in the original ROMAN analysis.
This GPC analysis shows compelling evidence from the ROMAN trial of AVA's clinical benefit across key parameters of SOM burden.
Details
- Title: Subtitle
- Benefit of Avasopasem Manganese on Severe Oral Mucositis in Head and Neck Cancer in the ROMAN Trial: Unplanned Secondary Analysis
- Creators
- Carryn Anderson - Department of Radiation Oncology University of Iowa Hospitals & Clinics, Iowa City, IA, USASamuel Salvaggio - International Drug Development Institute (Belgium)Mickaël De Backer - International Drug Development Institute (Belgium)Jean-Christophe Chiem - International Drug Development Institute (Belgium)Gary Walker - Banner MD Anderson Cancer CenterDeborah Saunders - NOSM UniversityChristopher M. Lee - Cancer Care NorthwestNeal Dunlap - University of LouisvilleEugene Kennedy - Galera Therapeutics, Inc., Malvern, PA, USARobert Beardsley - Galera Therapeutics, Inc., Malvern, PA, USABenton Schoen - Galera Therapeutics, Inc., Malvern, PA, USAMarc Buyse - International Drug Development Institute (Belgium)
- Resource Type
- Journal article
- Publication Details
- Advances in radiation oncology, Vol.10(1), 101674
- DOI
- 10.1016/j.adro.2024.101674
- PMID
- 39678920
- PMCID
- PMC11638593
- NLM abbreviation
- Adv Radiat Oncol
- ISSN
- 2452-1094
- eISSN
- 2452-1094
- Publisher
- Elsevier Inc
- Grant note
- Galera Therapeutics, Inc (Galera)Galera
Funding for this Global Pairwise Comparison of the ROMAN study (NCT03689712 available fromwww.clinicaltrials.gov) was provided by Galera Therapeutics, Inc (Galera). Medical editorial support (assembling tables and figures, collating author comments, copyediting, factchecking, and referencing) and graphic services were provided by AOIC, LLC, and were funded by Galera.
- Language
- English
- Electronic publication date
- 11/2024
- Date published
- 01/2025
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9984746216002771
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