Abstract
898P Meta-analysis of two placebo-controlled trials of avasopasem manganese (AVA) in patients with locally advanced, head & neck cancer (LAHNC)
Annals of oncology, Vol.34(Suppl. 2), p.S573
10/2023
DOI: 10.1016/j.annonc.2023.09.2043
Abstract
Background
Oral mucositis (OM) is severe in up to 70% of patients receiving standard chemoradiation (7 weeks of RT and concurrent cisplatin). Cisplatin contributes to the acute toxicity (acute kidney injury, tinnitus, myelosuppression) during treatment but also causes irreversible chronic kidney disease (CKD) in up to 30% of patients in the years following treatment. Two randomized, placebo-controlled, blinded studies, ROMAN (NCT03689712) and GT-201 (NCT02508389), evaluated avasopasem 90mg (AVA) for the reduction of severe OM (SOM, WHO grade 3-4) and both met their primary endpoints.
Methods
The ROMAN phase 3 (ITT N=407) and GT-201 phase 2b trials (ITT placebo and 90 mg N=144) results were aggregated using conventional methods for fixed-effects meta-analysis. In ROMAN, prospectively defined follow-up of serum creatinine (sCr) and estimated glomerular filtration rates (eGFR) were assessed every 3 months for 1 year following 7 weeks of CRT.
Results
The meta-analysis of ROMAN and GT-201 (N=551 [313 AVA/238 PBO]) showed a 19% relative reduction in SOM incidence (52% vs 64%; P=0.0053), 58% relative reduction in SOM duration (median, 8 vs 19 days; P=0.0002), 32% reduction in Grade 4 incidence (22% vs 32%; P=0.0102), and 28% delay in median days to SOM onset (median 50 vs 39 days; P=0.0005). Adverse event frequencies were mostly comparable between treatment groups with a trend towards reduction of certain IMRT- and cisplatin-related toxicities including tinnitus which was reported less with AVA in both studies. At 1-year follow-up, AVA was associated with significant improvements in preservation of eGFR (P=0.0008) and sCr (P=0.006) levels vs PBO. Grade 3+ CKD results through 12 months show 10% AVA vs 20% PBO (relative risk 0.55, P=0.0043).
Conclusions
AVA produced statistically significant, clinically meaningful improvement of SOM vs PBO that was consistent across multiple measures of SOM, with an adverse event profile consistent with expectations for IMRT/cisplatin. At 1-year follow-up, AVA appears to reduce cisplatin-related CKD in the study population.
Details
- Title: Subtitle
- 898P Meta-analysis of two placebo-controlled trials of avasopasem manganese (AVA) in patients with locally advanced, head & neck cancer (LAHNC)
- Creators
- N. Dunlap - University of LouisvilleC. Anderson - University of IowaC. Lee - Cancer Care NorthwestJ. Kelley - University of Tennessee Medical CenterG. Walker - The University of Texas MD Anderson Cancer CenterV. Bar-AdD. Miller - Jersey Shore University Medical CenterV. King - St. Mary's HospitalA. Peddada - Renown Regional Medical CenterD. CiubaF. Vincent - Centre intégré universitaire de santé et de services sociaux de la Mauricie-et-du-Centre-du-QuébecB. Muzyka - East Carolina UniversityA. Gillespie-Twardy - Hematology Oncology AssociatesS. SonisE. KennedyD. Saunders - Health Sciences North
- Resource Type
- Abstract
- Publication Details
- Annals of oncology, Vol.34(Suppl. 2), p.S573
- DOI
- 10.1016/j.annonc.2023.09.2043
- ISSN
- 0923-7534
- eISSN
- 1569-8041
- Language
- English
- Date published
- 10/2023
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9984487660302771
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