Appeal type: Formulary Exception
Decision: Upheld

Diagnosis: Glioblastoma Isocitrate Dehydrogenase (IDH)- wild type.
Treatment Xpovio.
The insurer denied coverage for Xpovio.
The denial is upheld.

This is an adult female with a history of a glioblastoma isocitrate dehydrogenase (IDH)- wild type. The reason for denial on prior review was that standard Xpovio policy does not allow coverage of the request medication unless the patient has a diagnosis of multiple myeloma or diffuse large B cell lymphoma (DLBCL). Formulary alternatives are noted to be lomustine, everolimus and temozolomide.

A letter of medical necessity indicated that the patient was diagnosed with IDH- wild type methylguanine-DNA [Deoxyribonucleic acid] methyltransferase (MGMT) promoter methylated glioblastoma, with further resection. She was treated with concurrent radiation and temozolomide followed by two cycles of adjuvant temozolomide with subsequent progression. She was subsequently started on bevacizumab. She had further disease progression and was treated with nivolumab and cyber knife radiosurgery to an area of progression. She had further progression of disease. It was noted that selinexor (Xpovio) was currently being studied in clinical trials newly diagnosed and recurrent glioblastoma and had patients who had a favorable response. It was her opinion and the opinion of the hospital multidisciplinary brain tumor board that she be treated with Selinexor. Her doctor noted that lomustine was not optimal treatment for her tumor.

Formulary drugs available are listed as temozolomide, lomustine and everolimus. The patient has already failed temozolomide. The formulary drugs have unique adverse reactions, lomustine having lower blood counts and nausea and vomiting. Adverse reactions from everolimus are mouth sores, of respiratory infections, ear infections and fever. Side effects from selinexor are fatigue, nausea, thrombocytopenia, decreased appetite, weight loss, diarrhea and vomiting among others. Both formulary medications and selinexor all have different adverse effects. All documentation sites the failure of temozolomide. There has been no trial and failure of either lomustine or everolimus.      

"Glioblastoma multiforme (GBM) is an aggressive neoplasm of the brain that has commonly led to disappointing patient outcomes. Despite medical advancements and increasing research efforts, GBM studies reveal a stagnant survival rate at the global level with only sluggish improvement over time. Modern neuro-oncology research places a heavy emphasis on pharmacological therapies. Through a broad database search, we accumulated and synthesized the GBM-related neuroimmunocytological literature to create a comprehensive and contemporary review. Based on our findings, we discuss the recent neurocytological treatment strategies for GMB and the results of the studies. Regorafenib, paxalisib, and dianhydrogalactitol (VAL-083) are showing initial promise to decrease disease progression." (Fiani, B. et al.) 

While temozolomide has been ineffective (as detailed in multiple notes), lomustine and everolimus have not as they have not been prescribed.     

There is no evidence in the peer-reviewed medical literature that selinexor would be more effective than any of the formulary drugs. There is no evidence in the current medical literature that selinexor has any efficacy in the treatment of glioblastoma and clinical trials are still ongoing to determine safety and efficacy. On review of current medical literature, there are only phase 1 trials for selinexor in glioblastoma. (Fiani B. et al.) All publications reflect preclinical models. It is not referenced for use in glioblastoma in National Comprehensive Cancer Network (NCCN) guidelines.                                         

The insurer's denial of coverage for Formulary Exception for Xpovio is upheld.