Appeal type: Experimental/Investigational
Decision: Overturned

The patient is a male with relapsed/refractory neuroblastoma who failed conventional chemotherapy and is suffering progressive disease. The patient was initially diagnosed with intermediate risk neuroblastoma involving a localized abdominal tumor. He was treated as per the Children's Oncology Group (COG) intermediate risk protocol with neoadjuvant chemotherapy, surgical resection, and adjuvant chemotherapy. Within months after completing therapy, he was diagnosed with widely metastatic relapsed neuroblastoma. He was treated with several cycles of intensive chemotherapy as per the COG high risk protocol but proved refractory to chemotherapy with progressive disease. He was subsequently treated as per a COG relapse protocol with chemo-immunotherapy (irinotecan, temozolomide, and dinutuximab) but had further progression of disease and required emergency spinal radiation for spinal cord compression by tumor. Cancer whole exome sequencing of his tumor revealed an activating NRAS mutation. Based on this finding, his oncologist wishes to treat him with the MEK inhibitor, Binimetinib (Mektovi), targeting the oncogenic RAS-RAF-MEK-ERK pathway as a molecular-targeted therapeutic strategy for palliative care. The health plan has denied coverage due to determination that the drug is considered experimental.

The health plan's determination is overturned. 

Yes, Binimetinib (Mektovi) is likely to be more beneficial than any standard treatment for the insured's life threatening disease.
Neuroblastoma is the most common extracranial solid tumor in children and those with relapsed disease carry a poor prognosis. The child under review unfortunately developed relapsed disease that has proven refractory to conventional chemotherapy and chemo-immunotherapy. Genomic sequencing of this child's tumor revealed an activating NRAS mutation. NRAS is a component of the RAS-RAF-MEK-ERK pathway, a signal transduction cascade considered to be one of the
primary oncogenic pathways attributed to cancer initiation, maintenance, and resistance to therapy. Over-activation of this pathway has been implicated frequently in relapsed neuroblastoma and, therefore, may serve as a potent therapeutic target in relapsed/refractory
cases. Indeed, MEK inhibition has proven in preclinical studies to inhibit oncogenic activity and a number of MEK inhibitors have been developed, gaining Food and Drug Administration (FDA) approval in certain adult cancers with RAS pathway aberrations. Binemetinib (Mektovi)
is a highly selective MEK1/2 inhibitor which has been shown to have potent anti-tumor activity in NRAS-mutated melanoma in adults. Building on these promising findings, several clinical trials have been developed to assess efficacy of MEK inhibitors in relapsed/refractory pediatric
solid tumors with MEK pathway mutations, including neuroblastoma (NCT02780128 and NCT02124772).
In the current landscape of cancer care, with improved access to molecular sequencing and the emergence of more targeted therapies, it is becoming widespread practice and the gold standard of care to treat genomic driver mutations with targeted therapy if available, especially when limited alternative options exist. Clinical trial development and FDA approval of targeted drugs for childhood cancers often lags far behind that in adults due, in part, to mandated preceding safety data in adults and the rarity of childhood cancers, leading to lower priority by pharmaceuticals and slower trial enrollment, among other factors. However, these hindrances should not preclude children in dire need of treatment options to be denied access to potentially
life-saving drugs. Binemetinib has the potential to stabilize this child's disease progression and even, perhaps, affect a partial response, offering him the possibility of more longevity with quality of life. There are no alternative therapeutic options for this child. Therefore, he should be
afforded the opportunity to receive binimetinib as a personalized targeted treatment approach for his aggressive life-threatening disease.