Appeal type: Experimental/Investigational
Decision: Upheld

Diagnosis: Malignant neoplasm.
Treatment: Gilotrif. 
The insurer denied coverage for Gilotrif. 
The denial is overturned. 

This is a female patient with a history of primary malignant neoplasm of right upper lobe of lung and secondary malignant neoplasm of bone.  Per a telemedicine visit with an oncology specialist, the patient was presenting to establish care for metastatic epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma.  The patient had received palliative radiation therapy, osimertinib and adjunctive denosumab.  Guardant 360 testing noted possible acquired osimertinib resistance and that consideration for targeting EGFR L858R/L718A may include afatinib.  The patient was reported to have been feeling better at the same dose of afatinib 40 milligrams (mg). The patient was currently on denosumab and it was noted that the patient would continue to receive these locally.  

As per Yu et al. (2014), "Patients with [epidermal growth factor receptor (EGFR)] mutant lung cancer derive significant therapeutic benefit from treatment with EGFR tyrosine kinase inhibitors (TKIs).  Unfortunately, acquired resistance is an inevitable consequence of this treatment strategy, with a broad variety of resistance mechanisms including acquired EGFR mutations (e.g., T790M) and activation of bypass signaling pathways...everal therapeutic strategies hypothesized to delay or overcome resistance have been tested in clinical trials, including 'next-generation' EGFR TKIs and rational combinations of targeted agents.  However, to date, there are no [Food and Drug Administration (FDA)] approved therapies for patients with acquired resistance to first-line EGFR TKI therapy.  There remains a critical need for more effective and better tailored treatments in this setting in order to match treatments to the individual patient and specific resistance mechanism at hand."

The scientific evidence is based on molecular cellular data and not clinical data to support the use of afitinib in this case.  The National Comprehensive Cancer Network (NCCN) Guidelines do not mention the EGFR L718A mutation in their recommendations. However, there are case studies that support the use of afatinib in patients with mutated non-small cell lung cancer (NSCLC).

Gilotrif does not have final approval from the appropriate regulatory bodies for this diagnosis.  However, it is not possible to have an approval by a regulatory body for each rare clinical situation.  Therefore, the final approval may not be amenable to be approved by regulatory and there are clinical scenarios such as this case where the drug needs to be approved by the insurer.     

This patient a good candidate for Gilotrif, based on the derived benefit so far.  Per the appeal application, the patient has already had clinically observed signs of benefit from afatinib 40mg daily obtained as a sample pack from the manufacturer.  Chest discomfort and appetite have improved and the patient has not had any recurrent cough or dyspnea since thoracentesis.     

Gilotrif is the best available treatment for this patient at this time.  Based on the limited literature, Gilotrif is an appropriate treatment given that it is targeted therapy for this patient at this time.  This is a rare clinical situation therefore, it is impossible to have a large study to prove efficiency.  However, there are documented similar cases in which afatinib has been successful, such as seen in Liu et al. (2018) literature.

Gilotrif is likely to be more beneficial than any of the standard treatments/procedures for this patient

The carrier's denial of coverage for Gilotrif should be overturned.