Avelumab: A Novel Anti-PD-L1 Agent in the Treatment of Merkel Cell Carcinoma and Urothelial Cell Carcinoma

Abstract

Long-term treatment in the setting of metastatic Merkel cell carcinoma (MCC) and urothelial carcinoma (UC) has shown that current first-line chemotherapeutic agents are losing effectiveness and that there are limited treatment options available outside of radiation therapy and surgical interventions. The use of immunotherapeutic agents such as monoclonal antibodies has been considered a promising alternative for cancers that progress despite treatment with radiation therapy, surgery, and/or chemotherapeutic agents. Cancer cells escape immune surveillance by interrupting immune checkpoint pathways, resulting in dysregulation of T-cell function and so preventing its antitumor effects. In early 2017, avelumab (BAVENCIO®), a PD-L1-blocking monoclonal antibody agent, was approved for the treatment of metastatic MCC and UC. Trials that evaluated avelumab for the treatment of metastatic MCC and UC were the JAVELIN Merkel 200 Trial and the JAVELIN Solid Tumor trial, respectively. Efficacy results for both trials showed positive overall response rate (ORR) and progression-free survival rate (PFS). A strong safety profile was also established for avelumab. This review provides a brief introduction to checkpoint inhibitors and focuses on the recently approved PD-L1 inhibitor, avelumab.

Severe Demyelinating Polyneuropathy and Cranial Neuropathy During Avelumab Treatment of Metastatic Merkel Cell Carcinoma

“…Immune checkpoint inhibitors revolutionized the treatment of some types of cancer and brought new hope to patients prolonging their survival. Same is seen with avelumab and treatment of MCC 4 . Because of their ability to modulate immune response, ICIs can lead to activation of autoreactive T cells resulting in unique irAEs 12 .…”

“…First-line therapy for disseminated MCC is immune checkpoint inhibitor (ICIs; avelumab, pembrolizumab, nivolumab) 2 . Avelumab is a PD-L1 (programmed death ligand 1)–blocking monoclonal antibody used for the treatment of MCC, urothelial carcinoma, and other metastatic or locally advanced solid tumors 3,4 . It acts by blocking the PD-L1 that is upregulated on cancer cells, thus restoring host's immune response to eliminate tumor cells.…”

Key differences between anti-PD-1/PD-L1 inhibitors

“…Все препараты по своему строению являются IgG1, что объясняет их более выраженную устойчивость и способность индуцировать антителозависимую клеточную цитотоксичность. Однако данная способность выражена только у авелумаба, в структуре которого присутствует Fc-фрагмент [21]. Данная модификация является причиной большей частоты развития инфузионных реакций, требующих проведения премедикации [22].…”

Immunotherapies and Combination Strategies for Immuno-Oncology

“…In an early study, a fully human IgG4 monoclonal antibody (mAb) against PD-1, known as nivolumab, showed impressive response rates in various tumors [ 27 ]. Since then different PD-1 and PD-L1 inhibitors have been successfully tested and FDA approved against various tumors [ 8 , 9 , 10 ].…”

“…Checkpoint inhibitors have had great success in treatments of cancers such as metastatic melanoma, non-small cell lung cancer (NSCLC), and renal cancers [ 7 ]. Over the last decade, while there have been hundreds of immunotherapy trials, many of which are currently in progress (clinicaltrials.gov), only some have led to approval of some of these inhibitors for treatment of different cancers [ 8 , 9 , 10 ]. Inhibitors of checkpoint molecules such as PD-1, PD-L1, cytotoxic T- lymphocyte-associated protein 4 (CTLA-4), T cell immunoglobulin and mucin domain 3 (TIM3), lymphocyte-activation gene 3 (LAG3), and V-domain Ig suppressor of T cell activation (VISTA) have and will continue to dramatically change the landscape of immunotherapy.…”