Avelumab

Avelumab is an intravenously administered human monoclonal antibody belonging to the immune checkpoint inhibitor class. It binds to programmed death-ligand 1, or PD-L1, on tumor cells and other cells in the tumor environment, preventing PD-L1 from interacting with PD-1 and related immune regulatory pathways. By blocking this immune checkpoint, avelumab can enhance T-cell-mediated immune activity against cancer cells. Avelumab is used as monotherapy for metastatic Merkel cell carcinoma and for first-line maintenance treatment of selected locally advanced or metastatic urothelial carcinoma after platinum-based chemotherapy without disease progression. It is also used in combination with axitinib for first-line treatment of advanced renal cell carcinoma in applicable regulatory settings. Avelumab is administered by intravenous infusion, with a standard adult dose of 800 mg every two weeks. Premedication with an antihistamine and acetaminophen is recommended before the first four infusions and may be continued when clinically appropriate. Treatment is generally continued until disease progression or unacceptable toxicity. Because immune checkpoint inhibition can cause inflammation in normal organs, patients require monitoring for immune-mediated reactions involving the lungs, liver, bowel, endocrine organs, kidneys, skin and other tissues, as well as infusion-related reactions.

Avelumab is a recombinant human IgG1 monoclonal antibody developed to block PD-L1 and restore antitumor immune activity. The U.S. Food and Drug Administration granted accelerated approval on 23 March 2017 for adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma, based primarily on the JAVELIN Merkel 200 clinical programme. FDA subsequently granted accelerated approval for locally advanced or metastatic urothelial carcinoma following platinum-containing chemotherapy in May 2017. The U.S. prescribing information currently includes previously treated locally advanced or metastatic urothelial carcinoma after platinum-containing chemotherapy and first-line maintenance treatment following platinum-containing chemotherapy without disease progression. FDA also approved avelumab in combination with axitinib for first-line treatment of advanced renal cell carcinoma in May 2019. In the European Union, Bavencio received conditional marketing authorisation on 18 September 2017 and was converted to a full marketing authorisation on 19 August 2020. Current European indications include metastatic Merkel cell carcinoma, first-line advanced renal cell carcinoma in combination with axitinib and first-line maintenance treatment of locally advanced or metastatic urothelial carcinoma following platinum-based chemotherapy without progression. Indian regulatory records include avelumab concentrate for solution for infusion and regulatory approval of additional indications. Key clinical programmes include JAVELIN Merkel 200, JAVELIN Bladder 100 and JAVELIN Renal 101.

Avelumab is used for selected adult patients with advanced cancers according to the applicable regulatory indication. In metastatic Merkel cell carcinoma, it is used as monotherapy in adults and, in the United States, in pediatric patients 12 years and older. In urothelial carcinoma, avelumab is used as first-line maintenance treatment in patients with locally advanced or metastatic disease that has not progressed following platinum-containing chemotherapy. In the United States, it is also indicated for patients with locally advanced or metastatic urothelial carcinoma whose disease has progressed during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy. In renal cell carcinoma, avelumab is used in combination with axitinib for first-line treatment of advanced disease in applicable jurisdictions. The precise approved population and treatment setting can vary between countries and product labels. Treatment selection should be based on cancer type, disease stage, previous treatment, response to platinum-based chemotherapy where relevant, overall clinical condition and the approved indication applicable to the specific jurisdiction.

Avelumab is administered by intravenous infusion at a recommended dose of 800 mg every two weeks for the approved adult indications. The infusion is generally administered over approximately 60 minutes. Patients should receive an antihistamine and acetaminophen before the first four infusions, with continued premedication considered according to previous infusion reactions and clinical judgment. When avelumab is used with axitinib for advanced renal cell carcinoma, axitinib is administered separately according to its approved dosing schedule. Treatment with avelumab is generally continued until disease progression or unacceptable toxicity. Dose reductions are not routinely used for avelumab itself; clinically significant adverse reactions are generally managed through treatment interruption or permanent discontinuation depending on their severity and type. Patients receiving treatment should be observed for infusion-related reactions and monitored for immune-mediated toxicity throughout therapy.

Common side effects of avelumab include fatigue, infusion-related reactions, nausea, diarrhea, decreased appetite, rash, swelling, musculoskeletal pain, urinary tract infection and headache. When avelumab is used with axitinib, adverse effects may also include hypertension, diarrhea, fatigue, nausea, hoarseness, decreased appetite, hypothyroidism, cough, shortness of breath and joint pain. Laboratory abnormalities such as changes in liver enzymes, blood counts, thyroid function or electrolyte levels may also occur. Infusion-related reactions are particularly relevant during early treatment and can include chills, fever, flushing, back pain, abdominal discomfort, shortness of breath or allergic-type symptoms. The frequency and severity of adverse reactions vary according to the treatment setting and combination therapy. Many non-serious adverse effects can be managed with supportive care and appropriate clinical monitoring.

Important serious risks associated with avelumab include immune-mediated pneumonitis, hepatitis, colitis, nephritis, thyroid dysfunction, adrenal insufficiency, hypophysitis, diabetes, severe skin reactions and other inflammatory disorders affecting normal organs. Serious or life-threatening infusion-related reactions can also occur and may require interruption or permanent discontinuation of treatment. Avelumab can cause immune-mediated inflammation even after treatment has been stopped, so new symptoms require appropriate clinical assessment. Patients receiving avelumab with axitinib may experience additional or overlapping toxicities, including hepatic, cardiovascular and other adverse effects associated with the combination. Rare immune-mediated neurological, cardiac, ocular or muscular complications may also occur. Patients should be monitored for symptoms such as new or worsening cough, breathing difficulty, persistent diarrhea, abdominal pain, jaundice, severe rash, reduced urine output, unusual weakness, severe headache, visual changes or changes in endocrine function. Treatment should be withheld or permanently discontinued when clinically significant immune-mediated toxicity develops according to its severity and applicable prescribing information.

Before starting avelumab, healthcare professionals should assess the patient's cancer diagnosis, previous treatments, autoimmune history, organ function and relevant endocrine, pulmonary, hepatic and renal conditions. Baseline and periodic laboratory monitoring should include liver function, kidney function, blood counts, thyroid function and other tests according to the clinical situation. Patients with active autoimmune disease or those receiving systemic immunosuppressive therapy require careful clinical assessment because immune checkpoint blockade may worsen immune-mediated conditions or reduce treatment activity in certain circumstances. Corticosteroids and other immunosuppressive medicines may be required to manage immune-related adverse events, although routine prophylactic immunosuppression is generally not used. Avelumab is not primarily metabolized through conventional hepatic CYP enzyme pathways, so classic CYP-mediated drug interactions are less prominent than with many oral targeted therapies. However, concomitant medicines and immune-modifying treatments should still be reviewed. Live vaccines should generally be avoided during treatment unless specifically advised by a healthcare professional. Patients should report all new symptoms promptly because immune-mediated toxicities can progress rapidly if not recognized and treated.

Prescribers should confirm the exact cancer indication, previous treatment history and applicable regulatory regimen before initiating avelumab. Baseline assessment should include liver and kidney function, blood counts, thyroid function and evaluation for pre-existing autoimmune, pulmonary, cardiac and endocrine conditions. Patients should receive clear counselling about early symptoms of immune-mediated toxicity and infusion reactions, including cough, shortness of breath, persistent diarrhea, abdominal pain, jaundice, severe rash, unusual fatigue, headache, dizziness and changes in urination. Premedication should be verified before the first four infusions and continued when clinically appropriate based on previous reactions. Pharmacists should confirm the 800 mg every-two-weeks schedule, intravenous route, infusion duration, preparation requirements and combination therapy when axitinib is prescribed. When avelumab is used as maintenance therapy after platinum-based chemotherapy, coordination with the oncology team is important to confirm that disease has not progressed before initiating maintenance treatment. Regular communication between oncology, pharmacy, nursing and laboratory teams helps identify immune-related adverse events early and supports appropriate treatment interruption or discontinuation.