Appeal type: Medical necessity
Decision: Upheld

Diagnosis: Glioblastoma.
Treatment: Stivarga.
The insurer denied coverage for Stivarga.
The denial is upheld. 

This is a male patient with a newly diagnosed glioblastoma (GBM).  The treating provider has proposed therapy with Stivarga as initial therapy as he has Methylguanine- Deoxyribonucleic acid (DNA) Methyltransferase (MGMT) unmethylated status.  The patient has a history of congenital atrioventricular conduction block status post pacemaker and recent diagnosis of glioblastoma. The gross total resection and pathology was read as grade IV glioblastoma MGMT unmethylated, isocitrate dehydrogenase (IDH) status.  The patient had left occipital craniotomy and gross total resection of tumor.  Per assessment, the patient is unable to obtain magnetic resonance imaging (MRI) of the brain due to his pacemaker.  The treatment discussed was regorafenib as first-line therapy off-label, given previous studies showing its effectiveness in treating recurrent glioblastoma. The patient's computed tomography (CT) scan of the head with contrast showed a hypoattenuating, peripherally contrast-enhancing lesion in the left occipital lobe abutting the ependyma.

As per Parisi et al. (2015), "Temozolomide (TMZ) is the first line drug in the care of high grade gliomas.  The combined treatment of TMZ plus radiotherapy is more effective in the care of brain gliomas then radiotherapy alone...The study found that the] combination of [radiotherapy (RT)] and TMZ improves long term survival in glioma patients." 

As per Binabaj et al. (2018), "[Glioblastoma (GBM)] patients with [O6-Methylguanine-DNA methyltransferase (MGMT)] methylation were associated with longer overall survival, although this effect was not detected for [progression-free survival (PFS)]...data showed a significant association with better [overall survival (OS)] and PFS, although further studies are warranted to assess the value of emerging marker in prospective setting in patients with glioblastoma as a risk stratification biomarker in clinical management of the patients."                                                         

As to date, there is no evidence to support the use of regorafenib to treat glioblastoma (GBM) as initial therapy. The National Comprehensive Cancer Network (NCCN) specifically addresses the treatment of unmethylated GBM and does not support the use of regorafenib as initial therapy.  The proposed use of regorafenib is currently unproven and not established for the proposed use in the front-line treatment of GBM. The use of Stivarga as initial therapy to treat GBM in place of radiation with or without Temodar is not consistent with accepted standards of practice and is not necessary. An ongoing trial with no published results does not establish medical necessity.  The NCCN continues to state that these patients should receive Temodar plus radiation, but acknowledge that benefit is likely to be lower.  No advancement has been made in the last 15 years in the treatment of these patients and other studies of agents such as Avastin have failed to demonstrate improvement.  

Stivarga is not considered medically necessary for this patient.

The health plan acted reasonably with sound medical judgment, and in the best interest of the patient.

The carrier's denial of coverage for Stivarga should be upheld.  The medical necessity is not substantiated.