Abstract
Effects of GC4419 (avasopasem manganese) on chronic kidney disease in head and neck cancer patients treated with radiation and cisplatin
Journal of clinical oncology, Vol.38(15_suppl), pp.12071-12071
05/20/2020
DOI: 10.1200/JCO.2020.38.15_suppl.12071
Abstract
12071
Background: Nephrotoxicity is a major complication of platinum-based chemotherapy and ranges in incidence from 31-68%. The effects of platinum-based chemotherapeutics on long-term renal outcomes (chronic kidney disease, CKD) profoundly affect morbidity and mortality. Concurrent chemoradiotherapy (CRT) including cisplatin is standard for locally advanced squamous cell head and neck cancer (HNC) but is accompanied by the risk of CKD. In a randomized, multi-center, placebo-controlled Phase 2b trial ( NCT02508389 ) of GC4419 (avasopasem manganese) in HNC patients receiving CRT, avasopasem reduced the duration, incidence, and severity of severe oral mucositis (Anderson et al, JCO 2019). Avasopasem did not appear to alter the safety profile of CRT in that trial, including incidence of adverse events of kidney injury or azotemia. Methods: Pre- and post-treatment markers of kidney function including blood urea nitrogen (BUN), serum creatinine (sCr), and estimated glomerular filtration rate (eGFR) were retrospectively evaluated for a subset of 52 of the trial patients who received 3 cycles x 100 mg/m
2
cisplatin plus placebo or 30 or 90 mg of avasopasem intravenously prior to RT, and 7 comparator patients who received the same CRT outside the study. Kidney function was evaluated between 3- and 24-months post-completion of cisplatin-radiation therapy by two-way analysis of variance (ANOVA) as defined by the Kidney Disease Improving Global Outcomes (KDIGO) CKD staging. Results: Baseline patient characteristics were skewed towards a male population but were balanced across all treatment arms with regards to baseline kidney function (comparator + placebo, n = 19; 30 mg GC4419, n = 18; 90 mg GC4419, n = 15). Treatment with 90 mg GC4419 demonstrated normal BUN values (10-20 mg/dL) at 3, 6, and 18 months and normal sCr values (0.6-1.2 mg/dL) between 3 and 24 months as compared to the placebo arm + comparator group, which exhibited statistically elevated BUN and sCr (p < 0.05). Treatment with 90 mg GC4419 also demonstrated significantly higher eGFR between 3 and 24 months post-chemoradiation (p < 0.05) compared to the placebo arm + comparator group. 90 mg GC4419 treatment significantly reduced the incidence of CKD compared to the placebo arm and comparator group, as determined by fold change in sCr values and eGFR measurements < 60 mL/min (stage G3a/b, G4, or G5 CKD). Conclusions: Avasopasem has the potential to reduce the incidence and severity of CKD in patients receiving cisplatin therapy. Clinical trial information: NCT02508389 .
Details
- Title: Subtitle
- Effects of GC4419 (avasopasem manganese) on chronic kidney disease in head and neck cancer patients treated with radiation and cisplatin
- Creators
- Emily J. Steinbach - University of IowaVarun Monga - University of IowaMuhammad Furqan - University of IowaDouglas Earl Laux - Jefferson City Medcl Grp, Columbia, MO;Diana Zepeda-Orozco - Nationwide Children's HospitalJennifer G. Jetton - University of IowaDeborah Saunders - Northeast Cancer CentreNeal Dunlap - University of LouisvilleAmarinthia Curtis - Spartanburg Regional Medical CenterRobert Fairbanks - Cancer Care NorthwestSarah Bell - University of IowaCarryn M. Anderson - University of IowaRobert Alan Beardsley - Galera Therapeutics, Inc., Malvern, PA;Jon Holmlund - Galera Therapeutics, Malvern, PA;Douglas Spitz - University of IowaBryan G. Allen - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Journal of clinical oncology, Vol.38(15_suppl), pp.12071-12071
- DOI
- 10.1200/JCO.2020.38.15_suppl.12071
- ISSN
- 0732-183X
- eISSN
- 1527-7755
- Grant note
- name: Galera Therapeutics, Inc.
- Language
- English
- Date published
- 05/20/2020
- Academic Unit
- Pathology; Internal Medicine; Stead Family Department of Pediatrics; Fraternal Order of Eagles Diabetes Research Center; Hematology, Oncology, and Blood & Marrow Transplantation; Radiation Oncology; Nephrology, Dialysis and Transplantation
- Record Identifier
- 9984314295502771
Metrics
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