Appeal type: Medical necessity
Decision: Upheld

Diagnosis: Metastatic cholangiocarcinoma.

Treatment: Idhifa (enasidenib).

The insurer denied coverage for Idhifa (enasidenib).

The denial is upheld. 

This is a female patient with metastatic cholangiocarcinoma. The treating provider has proposed therapy with Idhifa based on isocitrate dehydrogenase 2 (IDH2) mutation found on Foundation One testing.

The patient has a history of metastatic cholangiocarcinoma. For this patient's clinical scenario, standard National Comprehensive Cancer Network (NCCN) options include Stivarga or FOLFIRI (Folinic acid + Fluorouracil + Irinotecan). The request of Idhifa is based on IDH2 mutation found on Foundation One testing. The use of therapy in off label fashion such as in this case is associated with no clinical benefit and will likely lead to toxicity without benefit. Furthermore, the use of next-generation sequencing (NGS) panel testing as a means to select anti-cancer therapy in advanced cancer remains an area of active research with ongoing studies. Therefore, Idhifa is not medically necessary for this patient.  

"Overall, our study provides a real-world experience of the impact of comprehensive genomic profiling (CGP) in a community-based academic National Cancer Institute (NCI) -designated cancer center serving a highly diverse patient population, where molecular testing is based on a two-tier testing algorithm. While recognizing that a 10% overall rate of management change that is based on CGP is very modest, its use in certain subsets, such as advanced non-small-cell lung carcinoma (NSCLC), where the impact currently is most significant appears to be justifiable and it has been found to be cost effective. In addition, we have identified multiple reasons for the relatively smaller clinical impact of CGP in other tumor types, despite a much larger proportion of patients with actionable genomic alterations reported ...Although issues, such as optimal timing, access to clinical trials, and consolidating genomic testing need to be addressed at an institutional level, reports from testing platforms need to be carefully interpreted and ideally discussed in molecular tumor boards to provide the best treatment option possible. More prospective trials are needed that would better inform our choices for personalized treatment by providing assessments of overall survival and quality of life with choosing targeted therapies that are based on CGP when compared to conventional therapies" (Singh, A.P., et al. 2020).

"Cholangiocarcinoma (CCA), albeit an orphan disease, is beginning to attract attention from investigators and industry at an accelerated pace, given its lethality. Sophisticated clinical trials will require improved methods to stratify CCA patients and the time has come to abandon the inclusion of all patients with biliary tract cancers into a single trial. Future trials must stratify patients according to their anatomic subtype, genetic drivers, and stage of disease.  Biomarker-guided information will also be imperative in the development of effective medical therapies for CCA..." (Rizvi, S., & Gores, G. J., 2017).

Le Tourneau, C., et al. (2015), "The use of molecularly targeted agents outside their indications does not improve progression-free survival compared with treatment at physician's choice in heavily pretreated patients with cancer. Off-label use of molecularly targeted agents should be discouraged, but enrolment in clinical trials should be encouraged to assess predictive biomarkers of efficacy."                                                       

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

The insurer's denial of coverage for Idhifa (enasidenib) is upheld. Medical necessity is not substantiated.