Appeal type: Experimental/Investigational
Decision: Overturned

Diagnosis: Neuroblastoma
Treatment: Chemotherapy Treatment Regimen (cyclophosphamide, topotecan and naxitamab)
The insurer denied the Chemotherapy Treatment Regimen (cyclophosphamide, topotecan and naxitamab).
The denial is overturned.

The patient is a female child with high risk, N-Myc (basic helix-loop-helix protein 37)-amplified neuroblastoma, diagnosed 3 years ago. She has failed standard therapy and relapsed. She was treated with dintuximab/irinotecan/temozolomide but had minimal response. The provider is now recommending treatment with cyclophosphamide, topotecan and naxitamab.

The health plan should cover the requested Chemotherapy Treatment Regimen (cyclophosphamide, topotecan and naxitamab).

The patient has failed all known standard chemotherapy, including dintuximab/irinotecan/temozolomide. Naxitamab is a GD2 (disialoganglioside GD2)-directed monoclonal antibody, which is highly expressed in various neuroectoderm-derived tumors and sarcomas. Naxitamab is administered to patients three times per week in an outpatient setting and is repeated every four weeks.

In one study, overall objective response was 75% [percent] (18/24), with complete response (CR) in 67% (16/24) and partial response in 8% (2/24).

The FDA (United States Food and Drug Administration) has granted an accelerated approval to naxitamab-gqgk (Danyelza) for use in combination with granulocyte-macrophage colony-stimulating factor as a treatment for pediatric patients one year of age and older and adult patients with relapsed/refractory high-risk neuroblastoma in the bone or bone marrow who have demonstrated a partial response, minor response, or stable disease to prior treatment.

NCI (National Cancer Institute) guidelines state that Chemotherapy combined with immunotherapy produces the best response rate and response duration of treatments for high-risk patients with disease progression. Natxitamab has been combined with several chemotherapy regimens. Topoisomerase I inhibitors, including the camptothecin derivatives topotecan and irinotecan, have been shown to have significant activity in pre-clinical studies and more recently in patients with recurrent and refractory neuroblastoma. These drugs inhibit the topoisomerase I enzyme in replicating cells leading to the induction of DNA (deoxyribose nucleic acid) single and double strand breaks resulting in cell death.

Topotecan alone and in combination with chemotherapies such as cyclophosphamide, etoposide or doxorubicin has been studied in several single and multi institutional phase I and II trials for patients with relapsed solid tumors. The Children's Oncology Group (COG) reported the largest experience with this regimen in patients with relapsed neuroblastoma. In COG P9642, 57 patients treated with topotecan and cyclophosphamide (TOPO/CTX) and 62 patients treated with topotecan alone for up to one year had a combined three-year progression-free survival of 4% and an overall survival of 15%.

Since the patient in this case has failed temozolomide and irinotecan in the past, the recommended chemotherapy regimen would be considered medically appropriate for this patient.