Appeal type: Medical necessity
Decision: Overturned

Diagnosis: Relapsed right infratemporal fossa embryonal rhabdomyosarcoma.

Treatment: Opdivo 40 milligrams (mg) per 4 milliliters (mL).

The insurer denied coverage for Opdivo 40mg/4mL.

The denial is overturned. 

This patient is a female child with a medical history of relapsed right infratemporal fossa embryonal rhabdomyosarcoma (RMS). The plan of treatment was to combine nivolumab [Opdivo] with ipilimumab. Opdivo is considered medically appropriate in this setting when combined with ipilimumab.

As for many children with recurrent cancer, there is no Food and Drug Administration (FDA)-approved standard option for this child and the treating physicians are left to suggest the most rational tumor-directed therapy based on recent clinical trial data and expected tolerability. The use of non-FDA-approved drugs for a specific condition is unfortunately common and standard of care in pediatric oncology. As detailed in the citations below, and stated most clearly in Hirschfeld et al. (2003), "More than 100 drugs have been approved by the Division of Oncology Drug Products of the FDA for the treatment of malignancies. Only 15 have pediatric use information in their labeling, which is less than 50% of the drugs commonly used in the treatment of pediatric malignancies..."

As such, it is common for pediatric oncologists to use a drug of a certain class for a pediatric and young adult tumor for which there is no FDA-approval as long as there is rationale based on preclinical and clinical trial data. Such rationale exists in this case.  

The Lancet Oncology recently published outcomes for children with recurrent rhabdomyosarcoma receiving nivolumab. The published findings, Davis et al (2020), states that "Nivolumab showed no significant single-agent activity in the common paediatric solid tumours. This study defines the recommended phase 2 dose and establishes a favourable safety profile for nivolumab in children and young adults, which can serve as the basis for its potential study in combinatorial regimens for childhood cancer." Thus, it is not supported to use single agent nivolumab for the patient reviewed in this case. The denial of single agent Opdivo was appropriate. However, the Children's Oncology Group (COG) has made data available to its members that 1 of 10 patients with recurrent rhabdomyosarcoma had a significant response to the combination of nivolumab with ipilimumab.

As per literature review, single agent nivolumab has limited activity in non-lymphoma solid tumors as studied here. Combination therapy with ipilimumab 1 milligram per kilogram and nivolumab 3 milligrams per kilogram is well tolerated and showed sporadic activity with one response in Ewing sarcoma and one response in rhabdomyosarcoma. Given the life-threatening condition, lack of any FDA-approved therapy, lack of other safe intervention options, it was appropriate and within standard of care for the treating physician to use a commercially available Opdivo (nivolumab) with Yervoy (ipilimumab) in the treatment of this patient. The prior denial should be overturned.

The health plan did not act reasonably with sound medical judgment, and in the best interest of the patient.

The carrier's denial of coverage for Opdivo 40 milligrams (mg) per 4 milliliters (mL) is overturned. The medical necessity is substantiated.