NCCN Guidelines Update Includes Injection for Cisplatin Ototoxicity in AYAs

The National Comprehensive Cancer Network (NCCN) has updated clinical practice guidelines for Adolescent and Young Adults (AYA) Oncology to include sodium thiosulfate injection (Pedmark) to aid in mitigating the risk of cisplatin-associated ototoxicity in pediatric patients with localized, non-metastatic solid malignancies.¹

“Patients have medical and psychosocial needs that are unique to their age range, which is why it's important to have specific guidelines for their care,” said Michael W. Bishop, MD, an assistant member of the department of Oncology, Comprehensive Cancer Center at St. Jude Graduate School of Biomedical Sciences. “In the most recent update of the AYA Oncology guidelines provided by the NCCN, there was an addition that was made for toxicities [regarding] considerations for the use of sodium thiosulfate to reduce the risk of ototoxicity that is associated with cisplatin in pediatric patients with localized non metastatic solid tumors.”

"Preventing or reducing the severity of hearing loss, as we would hope that sodium thiosulfate does, could lead to improved psychosocial, emotional, and overall quality of life outcomes in cancer survivors," according to an expert in Rehabilitation Services at St. Jude Children's Hospital.

By updating the AYA Oncology guidelines, the idea is to identify challenges specific to the pediatric and young adult population, recommend unique interventions, educate providers, discuss lasting challenges, and considerations for disease management with the intent of making treatment more tolerable, improving outcomes, and encouraging clinical trial participation.

In a separate interview with CancerNetwork^®, Johnnie Bass, AuD, PhD, a research audiologist in Rehabilitation Services at St. Jude, discussed how the injection could impact quality of life if data continue to be positive.

“Preventing or reducing the severity of hearing loss, as we would hope that sodium thiosulfate does, could lead to improved psychosocial, emotional, and overall quality of life outcomes in cancer survivors,” Bass said. “With sodium thiosulfate recently emerging as a promising drug in the reduction and prevention of cisplatin ototoxicity, the future certainly looks more hopeful for our cancer survivors.”

Sodium thiosulfate injection was approved by the FDA in September 2022 to help decrease the risk of hearing loss in patients 1 month or older with localized, non-metastatic solid tumors who will receive treatment with cisplatin.² The injection was evaluated in 2 clinical trials: the phase 3 SIOPEL6 trial (NCT00652132) in a pediatric population with stage I to III childhood liver cancer and the phase 3 COG ACCL0431 study (NCT00716976) in newly diagnosed germ cell tumors or other malignancies being treated by cisplatin.

Data from the SIOPEL6 study indicated that patients who received sodium thiosulfate and cisplatin had a hearing loss rate of 39% vs 98% among those who were given cisplatin alone (HR, 0.58; 95% CI, 0.40-0.83). Additionally, 44% of patients in the COG ACCL0431 trial who were given sodium thiosulfate and cisplatin had hearing loss vs 58% in the cisplatin alone arm (HR, 0.75; 95% CI, 0.48-1.18).

Common adverse effects observed in the trials included vomiting, nausea, hypernatremia, hemoglobin decrease, and hypokalemia.

“This could have a major impact if the studies continue to show positive results,” Bass explained. “Hearing loss is a serious medical condition that impacts communication in all areas of life. Studies have shown it has been associated with an increased risk of poor academic achievement, higher unemployment rates for adults, reduced social attainment, emotional distress such as depression and anxiety, neurocognitive deficits, and generally poor quality of life when compared with individuals with normal hearing.”

Prior to the advent of sodium thiosulfate, pediatric patients with cancer undergoing treatment with cisplatin historically underwent routine hearing evaluations to detect and manage ototoxicities, Bass said. Other protocols include cisplatin dose reduction or selecting a treatment strategy with fewer ototoxicities such as carboplatin.

However, treatment modifications are not always feasible for some diagnoses, she explains. Due to this, monitoring hearing before, during, and after treatment is “even more important,” according to Bass. This provides time to assess whether timely rehabilitative recommendations are needed, including hearing aids, cochlear implants, and educational accommodations.

Although sodium thiosulfate may impact the way patients are treated, Bass cautions that routine hearing evaluations are still necessary.

“With the administration of sodium thiosulfate in conjunction with cisplatin, the expectation is that hearing loss will be prevented or minimized without having to modify the treatment plan,” she said. “But until there are more studies that are published on the long-term impact of sodium thiosulfate, I believe routine hearing evaluation should remain the gold standard in monitoring for ototoxicity, particularly in pediatric patients receiving cisplatin.”

Bishop also noted that clinical trials are ongoing assessing how toxicity from other chemotherapy agents may impact the use of sodium thiosulfate in select patient populations, such as those with germ cell tumors. He emphasized that drug interaction is going to be an important focus of future research.

“As new clinical trials come up that incorporate new investigational agents to standard therapies in a prospective fashion for solid tumors, it's going to be important to characterize any interactions of sodium thiosulfate with those drugs to ensure that its administration is not going to affect drug metabolism, safety, or efficacy of those agents,” Bishop concluded.

Recently, the FDA granted orphan drug designation exclusivity to sodium thiosulfate injection for the prevention of hearing loss in the aforementioned pediatric population.³

References

1. Fennec Pharmaceuticals announces updated NCCN clinical practice guidelines recommend Pedmark® (sodium thiosulfate injection) to reduce the risk of cisplatin-induced hearing loss in pediatric patients. News release. January 25, 2023. Accessed February 13, 2023. http://bit.ly/3jRDMTZ
2. FDA approves sodium thiosulfate to reduce the risk of ototoxicity associated with cisplatin in pediatric patients with localized, non-metastatic solid tumors. News release. FDA. September 20, 2022. Accessed February 13, 2023. https://bit.ly/3DLjVgC
3. Fennec Pharmaceuticals announces Pedmark® (sodium thiosulfate injection) receives orphan drug exclusivity from U.S FDA. News release. Fennec Pharmaceuticals. January 31, 2023. Accessed February 13, 2023. bit.ly/3HPPnw4