FDA D.I.S.C.O. Burst Edition: FDA approval of Pedmark (sodium thiosulfate) to reduce the risk of ototoxicity associated with cisplatin in pediatric patients 1 month and older with localized, non-metastatic solid tumors
Welcome back to the D.I.S.C.O., FDA’s Drug Information Soundcast in Clinical Oncology, Burst Edition, brought to you by FDA’s Division of Drug Information in partnership with FDA’s Oncology Center of Excellence. Today we’ll provide a quick update on a recent FDA cancer drug approval.
On September 20, 2022, the FDA approved sodium thiosulfate (brand name Pedmark) to reduce the risk of ototoxicity associated with cisplatin in pediatric patients 1 month and older with localized, non-metastatic solid tumors.
Efficacy was evaluated in two multicenter open-label, randomized controlled trials in pediatric patients undergoing treatment with cisplatin-based chemotherapy for cancer: SIOPEL 6 and COG ACCL0431.
SIOPEL 6 enrolled 114 patients with standard risk hepatoblastoma undergoing 6 cycles of perioperative cisplatin-based chemotherapy. Patients were randomized 1:1 to receive cisplatin-based chemotherapy with or without sodium thiosulfate administered at various doses based on actual body weight. The primary outcome was the percentage of patients with Brock Grade greater than or equal to 1 hearing loss, assessed using pure tone audiometry after treatment or at an age of at least 3.5 years, whichever was later. The incidence of hearing loss was lower in the sodium thiosulfate and cisplatin arm at 39% compared with the cisplatin alone arm at 68%, with an unadjusted relative risk of 0.58.
COG ACCL0431 enrolled 125 pediatric patients with solid tumors undergoing a chemotherapy regimen including cumulative cisplatin doses of 200 mg/m2 or higher, with individual cisplatin doses to be infused over 6 hours or less. Patients were randomized 1:1 to receive cisplatin-based chemotherapy with or without sodium thiosulfate. Efficacy was evaluated in a subset of 77 patients with localized, non-metastatic solid tumors. The primary outcome was hearing loss according to American Speech-Language-Hearing Association criteria, assessed at baseline and 4-weeks after the final course of cisplatin. The incidence of hearing loss was lower in the sodium thiosulfate and cisplatin arm at 44% compared with the cisplatin alone arm at 58%, with an unadjusted relative risk of 0.75.
The most common adverse reactions in the two trials were vomiting, nausea, decreased hemoglobin, hypernatremia, and hypokalemia.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
Full prescribing information for these approvals can be found on the web at www.fda.gov/drugsatFDA.
Health care professionals should report serious adverse events to FDA’s MedWatch Reporting Program at www.fda.gov/medwatch.
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