Appeal type: Experimental/Investigational
Decision: Overturned

Cancer
Pharmacy/Prescription Drugs

The patient is a male with a history of recurrent neuroblastoma. He initially presented for care with a large right suprarenal mass. He was classified as having intermediate risk disease, with anapestic large cell, unfavorable histology and N-MYC negative. He was started on chemotherapy as per the Children's Oncology Group (COG) protocol and received treatment with carboplatin, etoposide, cyclophosphamide, doxorubicin. He had surgical resection of the disease. However, he had relapse of his disease diagnosed after he had leg pain and abdominal pain. He had disease in the liver, retroperitoneum, and bone marrow. His tumor was noted to be non-avid on metaiodobenzylguanidine (MIBG) imaging. He was subsequently treated per the COG protocol ANBL1531 Arm A with cyclophosphamide, topotecan, vincristine, doxorubicin, cisplatin and etoposide. However, imaging showed progression of his disease. He was then started on treatment per the COG protocol ANBL1821 with irinotecan, temozolomide and Dinutux. Unfortunately, at this time is noted to have two large masses in the spine causing left-sided weakness and compression of the caudal equina and a facial mass causing pain. The provider is trying to determine what the next best therapy is for the patient. Based on Foundation One testing the tumor tissue was found to be NRAS positive. The provider is now recommended Mektovi as treatment of the patient's disease as the best potential treatment option going forward. The use of Mektovi is under review.

The health plan's determination is overturned.

Yes, the proposed health service or treatment with Mektovi 15 mg OR tabs is likely to be more beneficial than any standard treatment or treatments for this patient's life threatening or disabling condition or disease. This patient has failed multiple treatment options for his neuroblastoma, progressing while on chemotherapy three times now. The provider has recommended Mektovi based on individualized tumor tissue testing which showed an NRAS mutation. There are no standard treatment options for this disease process after multiple relapses, and the therapy must be selected based on the patient's individual situation. Per the National Cancer Institute (NCI), treatment options for refractory neuroblastoma includes chemotherapy combined with immunotherapy (temozolomide, iriontecan and dinutuximab - which this patient has tried and failed), 131I-MIBG therapy (which will not work for this patient who does not have MIBG positive disease), chemotherapy (topotecan with cyclophosphamide, etoposide, or temozolomide with irinotecan - which again the patient has tried and failed), or ALK inhibitors for patients with ALK mutations (this patient does not have an ALK inhibitor).
The use of Mektovi has been studied in some groups of patient with neuroblastoma. As per Woodfield et al, neuroblastoma tumor cells show a range of sensitivities to Mektovi, representing a potential new therapeutic strategy for neuroblastoma. Tanaka et al noted also that MEK inhibitors are a promising therapeutic option for certain neuroblastoma patients. Johnsen et al also reported that this medication acts in synergy with CDK4/6 inhibitors to suppress tumor growth in neuroblastoma models.
Given the failure of other methods of therapy, the lack of "standard" treatment options, the knowledge of the NRAS mutation in the patient's individual tumor, and the current literature, the use of Mektovi in this case is likely to offer this child the best chance at survival from his cancer. He has a life-threatening disease and he will likely not survive very long without this treatment.

Therefore, based on the clinical information provided for review, and the current standards of care in the field, the use of Mektovi 15 mg OR tabs is appropriate at this time.