PP1020 - PEDMARK Prevents Cisplatin-Induced Hearing Loss in Children and Young Adults Without Impact on Survival: A Pooled Analysis

Abstract:
Cisplatin is a standard therapy to fight cancer but is highly ototoxic, causing permanent and irreversible hearing loss in 60% of treated children. We conducted a pooled analysis of 2 pivotal studies (ACCL0431, SIOPEL-6) of cancer patients (ages 1 month to 18 years) to assess the safety and efficacy of PEDMARK for reducing cisplatin-induced hearing loss. Results show the group that received PEDMARK 6 hours after each cisplatin infusion (N=118) experienced 39% hearing loss compared to 65% in the no-treatment group (N=116), (p=0.0001). Importantly, there was no significant difference in survival outcomes in children and young adults undergoing cisplatin chemotherapy.

Summary:
Rationale
There is an unmet clinical need for a safe and effective treatment to prevent cisplatin-induced hearing loss (CIHL) in children and young adults receiving cisplatin for cancer treatment. Cisplatin is a standard therapy for many cancers but is highly ototoxic, causing permanent and irreversible hearing loss in 60% of treated children. CIHL profoundly diminishes the quality of life in children and young people of all ages, affecting speech, language, social development and life opportunities.

PEDMARK (anhydrous sodium thiosulfate solution) has been approved by the FDA, EMA, and MHRA for preventing CIHL. However, there has been reluctance to prescribe it to all patients.

Methods
We conducted a pooled analysis of two pivotal studies, ACCL0431 and SIOPEL 6 to determine the safety and efficacy of PEDMARK (STS) in patients being treated for cancer with cisplatin. The analysis included 234 participants (ages 1 month to 18 years), with 116 in the no-STS arm, and 118 in the STS arm. There were no statistical differences between the groups in relation to age, weight, age category ( < 5 years, > 5 years), sex distribution, race, or tumor category.

Results show a significant reduction in CIHL in participants who received PEDMARK 6 hours after each cisplatin infusion, with 39% experiencing hearing loss compared to 65% in the no-treatment group, (p=0.0001). Importantly, there was no significant difference in overall survival, event-free survival or objective response rate to chemotherapy between treatment groups.

Conclusion
The pooled analysis demonstrates that PEDMARK significantly reduces the risk of CIHL without compromising survival outcomes in children and young adults undergoing cisplatin chemotherapy. These findings support the use of PEDMARK as a safe and effective treatment for preventing CIHL in children and young adults.