Appeal type: Medical necessity
Decision: Upheld

Diagnosis: Peripheral nerve sheath tumor

Treatment: Xpovio (80 milligrams [mg] once weekly) 40 mg oral (OR) tablet pack (TBPK)

The insurer denied coverage for Xpovio (80 mg once weekly) 40 mg OR TBPK.

The denial is upheld.

This patient is a male with a peripheral nerve sheath tumor. The treating provider has requested Xpovio (selinexor) based on a liposarcoma study, some preclinical studies, and an opinion piece/case report. The request was denied by the plan as the plan will not cover Xpovio if the treatment of the condition is not supported by the National Comprehensive Cancer Network (NCCN) Guidelines and the Food and Drug Administration (FDA) labeling.

Malignant peripheral nerve sheath tumors (MPNSTs) are an uncommon but devastating tumor of peripheral nerve, representing only approximately ten percent of tumors encountered by a peripheral nerve surgeon. The incidence of MPNSTs in the general population is 0.001 percent. MPNSTs, which are classified as malignant soft tissue sarcomas, can arise from pre-existing plexiform neurofibromas or perineuriomas, or normal nerves. 

As such, therapy for these tumors would follow the NCCN Soft Tissues Sarcoma Guidelines for unclassified soft tissue sarcoma. Xpovio is not listed by the NCCN as therapy for this tumor type or for soft tissue sarcoma at large. Case series, opinion pieces, preclinical studies, and studies of Xpovio in unrelated tumors, are not acceptable evidence of efficacy. Therefore, the requested therapy would not be considered medically necessary, in this case.

"INDICATIONS AND USAGE:
XPOVIO is a nuclear export inhibitor indicated in combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an antiCD38 monoclonal antibody." (Xpovio Package Insert)

"Selinexor-dexamethasone resulted in objective treatment responses in patients with myeloma refractory to currently available therapies." (Chari, A., et al, 2019)

"Selinexor (XPOVIO) is a first-in-class, oral, small molecule Exportin-1 (XPO1) inhibitor that is being developed by Karyopharm Therapeutics for the treatment of cancer. Selinexor (in combination with dexamethasone) received accelerated approval in the USA in July 2019 for the treatment of adult patients with relapsed or RRMM." (Syed Y. Y., 2019)

"Purpose: Antitumor activity in preclinical models and a phase I study of patients with dedifferentiated liposarcoma (DD-LPS) was observed with selinexor. We evaluated the clinical benefit of selinexor in patients with previously treated DD-LPS whose sarcoma progressed on approved agents.

Methods: SEAL was a phase II-III, multicenter, randomized, double-blind, placebo-controlled study. Patients age 12 years or older with advanced DD-LPS who had received two-five lines of therapy were randomly assigned (2:1) to selinexor (60 mg) or placebo twice weekly in 6-week cycles (crossover permitted). The primary end point was progression-free survival (PFS). Patients who received at least one dose of study treatment were included for safety analysis. (Registration: ClinicalTrials.gov identifier: NCT02606461)

Patients with advanced, refractory DD-LPS showed improved PFS and time to next treatment with selinexor compared with placebo. Supportive care and dose reductions mitigated side effects of selinexor. Prospective validation of calbindin 1 (CALB1) expression as a predictive biomarker for selinexor in DD-LPS is warranted." (Gounder, M. M., et al, 2022)

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

The insurer's denial of coverage for Xpovio (80 milligrams [mg] once weekly) 40 mg oral (OR) tablet pack (TBPK) is upheld. Medical necessity is not substantiated.