Appeal type: Medical necessity
Decision: Upheld

Diagnosis: High grade glioma
Treatment:  Xpovio 80mg, Pre-service
The insurer denied the  Xpovio 80mg, Pre-service
The denial is upheld

The patient is a female with diffuse astrocytoma, isocitrate dehydrogenase (IDH)-wild type, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutation positive, O[6]-methylguanine-DNA methyltransferase (MGMT) promoter unmethylated. The patient's other medical problems include migraines and seizures. 

The patient presented with a seizure and was found to have two right frontal masses. She underwent resection and pathology was positive for a grade II astrocytoma.   She then was treated with adjuvant temozolomide plus radiation followed by temozolomide maintenance.  She developed progression of disease. Plan is for treatment with Xpovio (selinexor).  

No, the proposed treatment with Xpovio is not medically necessary.
The patient has a grade II astrocytoma. Request is for treatment with selinexor. Exportin-one (XPO-1) is a major nuclear export protein of macromolecular cargo frequently overexpressed in cancer. Selinexor is a first-in-class, oral Selective-Inhibitor-of-Nuclear-Export (SINE) compound that impedes XPO-1 (Syed YY).

There are no studies of selinexor to treat grade II astrocytomas (www.pubmed.gov; searched). Selinexor to treat grade II astrocytomas is not supported by the National Comprehensive Cancer Network (NCCN) Guidelines.

There is one phase II study of selinexor to treat 60 patients with glioblastoma multiforme (GBM) (Lassman AB, Wen PY, van den Bent MJ, et al.) Twenty-eight percent of patients had a measurable decrease in tumor size and serious adverse events occurred in 34% of patients with one fatality. Selinexor is not benign treatment. 

The request is made based on the prior meeting presentation of the above phase II study (Andrew B. Lassman, Patrick Y. Wen, Martin J. Van Den Bent, Scott Randall Plotkin, Anna Maria Elisabeth Walenkamp, Xiu Huang, Karla Rodriguez-Lopez, Michael G. Kauffman, Sharon Shacham, Morten Mau-Srensen)

In summary, the proposed treatment is not medically necessary as it is not in accordance with generally accepted standards of medical practice and it is not clinically appropriate and considered effective for this patient's illness.

Yes, the health plan acted reasonably, with sound medical judgment and in the best interest of the patient.
Efficacy of treatment of cancer depends on specific cancer being treated. The side effects of treatment depend on the response of the body to treatment and are to a great extent independent of the cancer being treated. 

The efficacy of selinexor to treat grade II astrocytoma is unknown. In the phase II trial of selinexor to treat glioblastoma serious adverse events occurred in 34% of patients with one fatality.  If treatment with selinexor had no side effects and no risk of fatal side effects it would make sense to try the treatment, given the data of efficacy that are extrapolations of the minimal efficacy of selinexor to treat glioblastoma. But selinexor does have side effects. One patient (of 72) died due to treatment and over a third had serious side effects. 

If you treat a patient with an agent that has side effects and the patient does not respond to the treatment, they die sooner than they would if just treated with supportive care. "Hail Mary" treatments often cause patients to die sooner then they would have with supportive care. Given the absence of data on efficacy in grade II astrocytoma and the known toxicity of this treatment, the plan's decision was in the best interest of the patient.