Appeal type: Medical necessity
Decision: Upheld

Diagnosis:  Metastatic melanoma in right axillary nodes

Treatment:  Inlyta

The insurer denied coverage for Inlyta. The denial upheld.

This patient is a male metastatic melanoma in right axillary nodes by biopsy.  He was treated with nivolumab and Yervoy.  Nivolumab was stopped due to development of a facial rash.  He completed 4 cycles of Yervoy, with a minor response. Axitinib and Keytruda are requested for approval.

Keytruda (pembrolizumab) is the first PD-1 inhibitor approved, and it was recently indicated for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation-positive, a BRAF inhibitor(1).  Pembrolizumab is able to achieve a dual blockade (PD-L1 and PD-L2r.  However, the combination with Axitinib is not well supported for melanoma, although it is well published and FDA approved for renal cell carcinoma.  Medical literature does not support the combination of Axitinib (Inlyta) with Pembrolizumab (Keytruda) in metastatic melanoma.  A phase II study demonstrated its single-agent activity in melanoma (Fruehaf, J.P., et al).  There is a 2019 study with topiralimab, but it was not found to be published with axitinib at all in melanoma.  

Per Sharon, E. et al. "Immunology-based therapy is rapidly developing into an effective treatment option for a surprising range of cancers.  We have learned over the last decade that powerful immunologic effector cells may be blocked by inhibitory regulatory pathways controlled by specific molecules often called "immune checkpoints."  These checkpoints serve to control or turn off the immune response when it is no longer needed to prevent tissue injury and autoimmunity.  Cancer cells have learned or evolved to use these mechanisms to evade immune control and elimination.  The development of a new therapeutic class of drugs that inhibit these inhibitory pathways has recently emerged as a potent strategy in oncology.  Three sets of agents have emerged in clinical trials exploiting this strategy . . . ." Per Rini, B.I., et al. "Among patients with previously untreated advanced renal-cell carcinoma, treatment with pembrolizumab plus axitinib resulted in significantly longer overall survival and progression-free survival, as well as a higher objective response rate, than treatment with sunitinib. (Funded by Merck Sharp & Dohme; KEYNOTE-426 ClinicalTrials.gov number, NCT02853331. opens in new tab.)"

Per Freuhauf, J.P., et al. in a preliminary report stated, "Conclusions: Axitinib has demonstrable single-agent activity in melanoma.  Preliminary analyses indicate that patients who achieve elevated dBP 90 mm Hg on therapy have longer survival associated with potent and selective inhibition of targeted VEGFRs."   Per the FDA approved Inlyta label (2019), regarding indications and usage, it states, "INLYTA is a kinase inhibitor indicated for the treatment of advanced renal cell carcinoma after failure of one prior systemic therapy" (1).  Medical literature does not support the use of Inlyta for melanoma outside the setting of a clinical trial.  The health care plan acted reasonably and with sound medical judgment and in the best interest of the patient.  Inlyta is not considered medically necessary for this patient.

The carrier's denial of coverage for Inlyta is upheld.  The medical necessity is not substantiated.