Appeal type: Medical necessity
Decision: Upheld

Diagnosis: Brain Tumor
Treatment: Xpovio, Pre-service

The insurer denied the Xpovio, Pre-service.
The denial is upheld.

The patient is a male with progressive grade 3 oligodendroglioma. His tumor is MGMT (O[6]-methylguanine-DNA methyltransferase) promoter methylated , IDH2 (isocitrate dehydrogenase 2) R172K (arginine 172 K) mutated, TERT (telomerase reverse transcriptase) promoter mutated, and has a NOTCH1 (Neurogenic Locus Notch Homolog Protein 1) deletion. Tumor mutation burden is 8 mutations/megabase.

The patient initially presented with altered olfaction and a generalized seizure. He was treated with maximal safe resection followed by concurrent proton irradiation and temozolomide. He then was treated with 9 cycles of maintenance temozolomide.

MRI (Magnetic resonance imaging) of the patient's brain after the 9 cycles of temozolomide showed a new focus of tumor. He was switched to PCV (Procarbazine Hydrochloride, Lomustine, Vincristine Sulfate). He was continued on PCV (Procarbazine Hydrochloride, Lomustine, Vincristine Sulfate) when he again developed progression of disease.

The patient's tumor involves the bilateral corpus callosum with bilateral cerebral edema. He has left hemiparesis, executive cognitive dysfunction and delusions.

The patient was started on bevacizumab. The tumor is behaving like a glioblastoma, although no re-biopsy has been performed.

Given the degree of edema, the patient's treating physicians do not want to treat with pembrolizumab. He is not a candidate for most clinical trials, given his steroid dependence. The plan is for treatment with selinexor.

This request was denied by the plan as it is not an FDA (United States Food and Drug Administration)-approved indication, and it is not supported by the NCCN (National Comprehensive Cancer Network) Guidelines recommendations.

A letter of appeal asserts that selinexor was denied because it is not an FDA (United States Food and Drug Administration)-approved indication and is not supported by the NCCN (National Comprehensive Cancer Network) Guidelines. The letter reads, "However, please note that the criteria are met - the patient has a clinical condition for which there is not appropriate formulary alternative, and this is ongoing treatment."

This is not evidenced to be ongoing treatment. The progress note indicated that the patient was not yet on selinexor and the plan policy for coverage for nonformulary agents refers to treatments that requested for FDA (United States Food and Drug Administration)-approved or NCCN (National Comprehensive Cancer Network)-supported for which there is no formulary alternative. The plan clearly does not cover non-formulary agents for treatments that are not supported simply because they are not on the formulary.

No, the requested Xpovio is not medically necessary.
The patient has a grade 3 oligodendroglioma. Xpovio (selinexor) is a first-in kind inhibitor of nuclear-cytoplasmic transport (1). Selinexor is currently used to treat multiple myeloma.

There are no published studies of selinexor to treat grade 3 gliomas (www.pubmed.gov).

The published studies of selinexor to treat glioblastoma (which is a grade 4 glioma) include pre-clinical research (not in patients; 2, 3, 4).

There is one, published, phase II study (5). The response rate in this trial was 8%, and some 28% of patients had some measurable decrease in tumor size. There was one death (out of 76 patients) due to treatment and 34% of patients had serious adverse events.

Given the absence of any data on the efficacy of this treatment on grade 3 gliomas, treatment with selinexor is not medically necessary. To be necessary (even in the absence of any alternative treatments), there must be established indications of efficacy for the treatment of this patient's clinical condition.

Yes, the health plan did act 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.

This patient has no known effective treatment options. If treatment with selinexor were to have 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 a patient were to be treated 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 than they would have with supportive care. Given the absence of data on efficacy in grade 3 oligodendroglioma and the known toxicity of this treatment, the plan's decision was in the best interest of the patient.