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Kidney Week

Abstract: SA-OR02

Effects of Avasopasem Manganese on Cisplatin-Induced AKI and CKD

Session Information

Category: Acute Kidney Injury

  • 102 AKI: Clinical, Outcomes, and Trials

Authors

  • Griffin, Benjamin R., University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
  • Huang, Chou-Long, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
  • Yamada, Masaaki, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
  • Swee, Melissa L., University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
  • Anderson, Carryn, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
  • Spitz, Douglas R., University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
  • Mapuskar, Kranti A., University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
  • Zepeda-Orozco, Diana, Nationwide Children's Hospital, Columbus, Ohio, United States
  • Kennedy, Eugene P., Galera Therapeutics Inc, Malvern, Pennsylvania, United States
  • Beardsley, Robert A., Galera Therapeutics Inc, Malvern, Pennsylvania, United States
  • Allen, Bryan, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
  • Jalal, Diana I., University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
Background

Nephrotoxicity is a major complication of cisplatin treatment in cancer patients. Rates of acute kidney injury (AKI) range from 31-68%, and about 30% of cancer survivors receiving cisplatin develop chronic kidney disease (CKD) within 1 year. Superoxide production plays a crucial role in cisplatin-induced AKI and CKD. Avasopasem (AVA) is a selective superoxide dismutase mimetic shown in phase 3 to reduce severe oral mucositis in head and neck cancer (HNC) patients receiving radiation plus high-dose cisplatin.

Methods

We analyzed renal function data from a phase 3, double-blinded, randomized trial that compared 90 mg AVA vs placebo (PBO) during cisplatin (weekly or every 3 weeks) and radiation therapy (CRT). Renal adverse events (AEs) were AKI, creatinine increase, or hypomagnesemia meeting grade 3+ criteria of the Common Terminology Criteria for Adverse Events for patients receiving cancer therapy. Creatinine was measured pretreatment, weekly during CRT, and then every 3 months for 1 year. CKD was staged at 1 year based on eGFR calculated using the CKD-EPI formula.

Results

241 patients were randomized to AVA and 166 to PBO. Grade 3+ AKI was reported in 0.8% of AVA group vs 3.8% of PBO, grade 3+ creatinine increase in 1.2% vs 2.4%, and grade 3+ hypomagnesemia in 3.3% vs 5.4%. 202 AVA and 149 PBO patients were available to assess at 1 year with 10.4% CKD incidence in AVA group compared to 20.1% in PBO (p=0.004), primarily due to a reduction in stage 3b or greater disease (Figure).

Conclusion

In patients with HNC receiving radiation plus high-dose cisplatin, AVA, a superoxide dismutase mimetic, was significantly associated with decreased incidence and severity of CKD, with a trend towards decreased incidence of grade 3+ acute renal AEs. AE profile was otherwise consistent with expectations for CRT.

Funding

  • Commercial Support – Galera Therapeutics, Inc.