Merkel cell carcinoma (MCC) is a rare form of non-melanoma skin cancer, most often caused by the Merkel cell polyamovirus gamma (MCPyV) in immunocompromised patients. The rarity of this disease has hindered development of new treatments for patients who have progressive or metastatic disease. Per the National Cancer Institute, the overall 5-year survival for patients with metastatic disease is estimated to be about 20%. Treatment recommendations for MCC are very limited and based on small sets of data. Chemotherapy accounts for the main form of treatment in metastatic disease and the regimens used often vary based on the individual practitioner. As the disease progresses through various forms of chemotherapy, patients with mMCC are left with no options for treatment. Urothelial carcinoma (UC) is the most common form of urinary tract malignancy. It accounts for the largest rates of death among bladder cancers. Treatment is often based on localized therapy including bladder irrigation and various forms of bladder surgery. As the disease progresses, patients are generally treated with platinum-based therapy.
Recently, the FDA granted accelerated approval to avelumab (Bavencio®) for treatment of metastatic Merkel cell carcinoma in patients 12 years and older who have progressed on platinum-based chemotherapy. Additionally, avelumab received accelerated approval for metastatic urothelial cancer in patients who have progressed on platinum-based chemotherapy. The need for newer medications for the treatment of mUC is not as clear as it is for mMCC, as avelumab is the fourth injectable immunotherapy agent to receive the mUC indication from the FDA. Avelumab is a PD-L1 receptor antagonist that is given every 2 weeks intravenously at a dose of 10 mg/kg. As part of the FDA’s accelerated approval requirements for avelumab, the manufacturers will be responsible for post-marketing reporting of various clinical endpoints.
The accelerated approvals for avelumab in these indications is based on findings from the JAVELIN stolid tumor studies. Approval for MCC was based on a phase 2 dose-expansion cohort study, while approval for mUC was based on a phase 1b trial. Both trials were conducted as single-arm, multicenter, non-randomized studies in patients who had progressed through, or were intolerable to platinum-based chemotherapy. Monitoring in both of these studies occurred every 6 weeks, and the average duration of treatment with avelumab was 7 doses. A summary of efficacy and safety outcomes for the respective trials is outlined in the following tables.
While the initial approvals for avelumab are for MCC and mUC, there is additional data suggesting activity in both non-small cell lung cancer and metastatic thymomas. In the phase 1/2 trials, there was some benefit noted in both patient groups. While these are currently off-label uses, it is expected that the manufacturer will further explore alternative indications for this agent.
There has been no proven benefit of one immunotherapy agent over another for mUC; however, the effects are thought to be class effects for both PD-1, and PD-L1 inhibitors. Avelumab is the first agent approved for MCC in nearly a decade, providing an option for patients who were previously left without any choices.
Currently, the criteria for use of avelumab within the VA Healthcare system are under development. It remains a non-formulary agent, despite the approved indications and recommendations in the National Comprehensive Cancer Network (NCCN) guidelines for both MCC and mUC. The average wholesale price (AWP) for a 200mg/10 mL single-dose vial is $1804.80. For a 70-kg patient, that equates to a cost of approximately $7219.20 per dose.