Gleevec denials: what the review data shows

Where the denial was overturned

Nature of Statutory Criteria/Case Summary: The patient has requested authorization and coverage for Gleevec (imatinib). In this case, the patient has a rare tumor called a schwannoma that has mutated the Neurofibromatosis type 2 (NF2) gene. He has exhausted surgery and radiation therapy and the provider has prescribed imatinib mesylate. The tumors appear to have activated platelet derived growth factor receptors and c-kit signaling that are inhibited by imatinib mesylate and other related tyrosine kinase inhibitors (TKIs). There is extensive data supporting the safety of this drug and it is available in generic form. In a case report, researchers showed stable disease in a patient with a rapidly progressive schwannoma growth who was treated with imatinib. Due to the rarity of the disease, there is a lack of extensive data on the use of TKIs in this clinical setting.

A 61-year-old male enrollee has requested the medication Gleevec (400 mg) daily for treatment of his melanoma. Findings: Two physician reviewers found that the patient was found to have metastases in the lung, bowel and brain. The brain metastases were treated with whole brain radiation, and he was started on a clinical trial of Gleevec to treat his other sites of metastasis. The patient was subsequently taken off the clinical trial of Gleevec. In view of the excellent response of the patient’s lung metastases to the Gleevec, it is now recommended that he resume treatment with this agent.Gleevec is a medication which, among other mechanisms of action, takes advantage of C-KIT mutations. These are common in gastrointestinal stromal tumors and Gleevec has been very effective in the treatment of such tumors.

Where the denial was upheld

A 62-year-old female enrollee has requested Gleevec 400mg. for treatment of her stage 4 adrenocortical carcinoma. Findings: Three physician reviewers found that adrenocortical carcinoma is difficult to treat because it is chemotherapy-resistant. A study showed that cisplatin in combination with etoposide and doxorubicin may have an effect in some patients with metastatic disease(Berruti and colleagues). In this patient’s case, she has only one functioning kidney, so the oncologist is appropriately hesitant about this therapy. There is a small series on the use of Gleevec for various solid tumors by Gross, et al. There were four adrenocortical carcinomas that showed no response to Gleevec. The use of gene array or immunohistochemistry to direct the choice of chemotherapy is not yet proven, especially since this is a measure of expression and not a confirmed somatic mutation.

The representative of a 46-year-old female enrollee has requested Gleevec for the treatment of the enrollee’s meningioma. Findings: The physician reviewer found that meningioma is a rare brain tumor typically treated with radiation and surgery. Various agents have been utilized for metastatic disease outside of the brain with very little proven efficacy. There is limited experience regarding systemic therapy for metastatic meningioma and the current evidence is largely anecdotal. Systemic therapy has only been used in a few patients with recurrent, unresectable malignant meningiomas. The phase II trials citied above involved a combination regimen of hydroxyurea and imatinib mesylate in small numbers of patients with higher grade brain tumors (not meningiomas).

These are outcomes from California’s external review program — an independent physician panel that binds the insurer. Every state has an equivalent process, and internal appeals succeed even more often. Cite the outcome record for Gleevecwhen you appeal: reviewers routinely find that denials like yours didn’t hold up.