Appeal type: Medical necessity
Decision: Upheld

Diagnosis: Hypoglycemia
Treatment: Piqray (Pi3 kinase inhibitor alpelisib)

The insurer denied coverage for Piqray.
The denial is upheld.

According to the medical records, the patient has a history of insulin-producing neuroendocrine tumor that cannot be excised surgically. She has been treated with corticosteroids, diazoxide, octreotide, everolimus, and acarbose, but the patient continues to have recurrent hypoglycemia. 

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

The patient has tried and failed conventional therapy, but the requested therapy is not supported by current peer reviewed literature for use in her clinical situation.      

Piqray (Pi3 kinase inhibitor alpelisib) is not considered medically necessary for this patient. Although one of the side effects of this medication is hyperglycemia, this reviewer has not found any current peer reviewed literature such as case reports, case series showing that this medication can be utilized for treatment of hypoglycemia. Therefore, the requested therapy, Piqray, is not supported to be medically necessary at this time. 

According to current literature in patients who are not candidates for surgery of hypoglycemia from a neuroendocrine tumor the treatment choices include these therapeutic choices to prevent symptomatic hypoglycemia: 

Diazoxide (which diminishes insulin secretion and is given in divided doses of up to 1200 mg (milligrams)/day) is sometimes used for controlling hypoglycemia. 

Octreotide, an analog of somatostatin (growth hormone-inhibitory hormone), inhibits growth hormone secretion but, in large doses, also inhibits the secretion of thyroid-stimulating hormone (TSH), insulin, and glucagon. While octreotide is highly effective in controlling the symptoms associated with glucagonomas, VIPomas (a type of neuroendocrine tumor), and carcinoid tumors, efficacy is less predictable for symptomatic patients with insulinoma. Nevertheless, it is a reasonable choice for patients with persistent hypoglycemia that is refractory to diazoxide.

Lanreotide, another somatostatin analog that is available internationally and in the United States for the treatment of acromegaly, appears to have similar clinical efficacy as octreotide, and is also available in a long-acting depot form (lanreotide SR). 

Verapamil and phenytoin have also been used with some success. However, none of these drugs is as effective as tumor resection.

According to the Food and Drug Administration (FDA) Package Insert, "PIQRAY is a kinase inhibitor indicated in combination with fulvestrant for the treatment of postmenopausal women, and men, with hormone receptor (HR)- positive, human epidermal growth factor receptor 2 (Her2)-negative, PIK3CA-mutated, advanced or metastatic breast cancer as detected by an FDA-approved test following progression on or after an endocrine-based regimen."

"A third class of therapeutic compounds, the PI3K inhibitors, has been introduced to the arsenal of targeted therapies overcoming endocrine resistance in hormone receptor-positive metastatic breast cancer. Alpelisib (PIQRAY) is the first of these novel agents yielding promising clinical results, giving an impetus to further development of tailored endocrine anticancer treatments. Herein, we review its pharmacodynamic and pharmacokinetic properties, safety and efficacy data, as well as Phase III Solar-1 trial, prompting FDA approval of alpelisib in hormone receptor-positive metastatic breast cancer harboring PIK3CA mutations." (Mavratzas, A. et al. 2020).

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

The insurer's denial of coverage for Piqray is upheld. Medical Necessity is not substantiated.