Avelumab
Overview
Avelumab is a fully human immunoglobulin G1 lambda monoclonal antibody that targets programmed death-ligand 1, a protein expressed on tumor cells and immune cells that enables cancers to evade immune surveillance. By binding to PD-L1, avelumab blocks its interaction with the PD-1 and B7.1 receptors on T lymphocytes, thereby restoring T-cell mediated anti-tumor immune activity. Unlike some other checkpoint inhibitors, avelumab retains an intact Fc region capable of mediating antibody-dependent cell-mediated cytotoxicity, which may contribute to direct tumor cell killing. Avelumab belongs to the class of immune checkpoint inhibitors and is administered by intravenous infusion. Its clinical importance lies in improving immune recognition and control of tumors across selected malignancies where immune suppression plays a central role in disease progression.
Background and Date of Approval
Avelumab received its first accelerated approval from the United States Food and Drug Administration on March 23, 2017 for the treatment of adults and pediatric patients aged 12 years and older with metastatic Merkel cell carcinoma. This marked the first FDA-approved therapy for this rare and aggressive skin cancer. On June 30, 2020, the FDA approved avelumab for maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma whose disease had not progressed following first-line platinum-containing chemotherapy. The FDA later approved avelumab in combination with axitinib for the first-line treatment of advanced renal cell carcinoma based on improved survival outcomes observed in large randomized clinical trials. These approvals established avelumab as an important agent in modern immuno-oncology practice.
Uses
Avelumab is indicated as monotherapy for adults and pediatric patients aged 12 years and older with metastatic Merkel cell carcinoma. It is also indicated for maintenance treatment of locally advanced or metastatic urothelial carcinoma in patients whose disease has not progressed after platinum-based chemotherapy. In addition, avelumab is approved in combination with axitinib for first-line treatment of advanced renal cell carcinoma. These indications reflect its role in restoring immune-mediated tumor control in settings where conventional therapies may have limited durability.
Administration
Avelumab is administered by intravenous infusion, typically over approximately 60 minutes, every two weeks. The standard recommended dose is 800 mg administered every two weeks until disease progression or unacceptable toxicity. Premedication with an antihistamine and acetaminophen is recommended prior to the initial infusions to reduce the risk of infusion-related reactions. When used in combination regimens, dosing schedules are coordinated with companion agents according to approved protocols. Treatment duration is individualized based on clinical response, tolerability, and ongoing oncologic assessment.
Side Effects
Common side effects associated with avelumab include fatigue, musculoskeletal pain, diarrhea, nausea, decreased appetite, rash, peripheral edema, and infusion-related reactions. These effects are generally related to immune activation or infusion processes and vary in frequency and severity among patients. Most common adverse effects are manageable with supportive care and appropriate medical supervision.
Warnings
Serious adverse events related to avelumab include immune-mediated toxicities such as pneumonitis, colitis, hepatitis, endocrinopathies including thyroid dysfunction and adrenal insufficiency, nephritis, and severe infusion-related reactions. Serious infections may also occur due to immune system modulation. Treatment interruption or permanent discontinuation may be required for severe or life-threatening toxicities. Avelumab may cause fetal harm, and pregnancy status should be evaluated prior to treatment initiation.
Precautions
Baseline assessments before initiating avelumab include evaluation of organ function, immune status, thyroid function, and review of prior autoimmune conditions. Patients should be monitored closely for signs of immune-mediated toxicity throughout treatment. Live vaccines should be avoided during therapy due to potential immune system effects. Drug interactions with avelumab are primarily related to additive immune modulation rather than traditional metabolic pathways, and caution is advised when combining with other immunomodulatory therapies.
Expert Tips
Patient selection for avelumab therapy should consider tumor type, disease stage, prior treatment exposure, and overall performance status. Baseline laboratory testing and ongoing monitoring are essential for early detection of immune-related adverse events. Patients should be counselled on infusion expectations and the importance of promptly reporting symptoms such as shortness of breath, diarrhea, abdominal pain, fatigue, or endocrine-related changes. Coordination among oncology specialists, nursing staff, and pharmacists supports safe infusion practices, timely toxicity management, and optimal therapeutic outcomes.