What is avelumab?
Avelumab is a human IgG1 lambda monoclonal antibody that blocks PD-L1.
How does avelumab work?
Avelumab works by binding to PD-L1 on tumor cells and tumor-infiltrating immune cells. This blocks PD-L1 from interacting with its receptors PD-1 and B7.1, leading to restoration of immune responses including anti-tumor immune response. Avelumab induces antibody-dependent cell mediated cytotoxicity in vitro.
What is this approved for?
Avelumab is indicated for the treatment of patients with metastatic Merkel cell carcinoma or patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-based chemotherapy.
What is the basis for this approval?
Eighty-eight patients with stage IV, chemotherapy-refractory Merkel cell carcinoma were evaluated in a phase II, multi-center, international, single-group, open-label trial. Patients did not have to have PD-L1 positive tumors to be enrolled. After a median follow-up of 10.4 months, 31.8 percent of patients had an objective response, including a 9 percent complete response rate (Lancet Oncol 2016;17:1374-1385).
Avelumab was evaluated in a phase Ib, multicenter, expansion cohort for patients with metastatic urothelial carcinoma after progression on a platinum-containing regimen. Forty-four patients received avelumab and were followed for a median of 16.5 months. The objective response rate to avelumab was 18.2 percent, including five complete responses. The median progression-free survival was 11.6 weeks and median overall survival was 13.7 months. At the time of publication, the median duration of response had not been reached (J Clin Oncol 2017;35:2117-2124).
How do you administer this drug?
Avelumab is administered by an IV infusion using a sterile, non-pyrogenic, low protein binding, in-line 0.2 micron filter over 60 minutes every 2 weeks and continued until disease progression or toxicity.
Are there any premedications needed for avelumab?
Premedication with an antihistamine and acetaminophen is recommended prior to the first four infusions of avelumab. For subsequent infusions premedication should be considered based on clinical judgment and the presence of infusion reactions.
What are the common side effects associated with avelumab (> or =10%)?
The following were common side effects of avelumab (all grades): fatigue (50%); infusion-related reaction (22%); peripheral edema (20%); musculoskeletal pain (32%); diarrhea (23%), nausea (22%), vomiting (13%); rash (22%); cough (18%); hypertension (13%); and increased AST (34%), ALT (20%), lipase (14%), anemia (35%), lymphopenia (49%), thrombocytopenia (27%).
What are the uncommon side effects associated with avelumab (less than 10%)?
Avelumab is associated with immune-mediated toxicities such as the following: pneumonitis (1.2%); hepatitis (0.9%); colitis (1.5%); adrenal insufficiency (0.5%); thyroid disorders (6%); type 1 diabetes (0.1%); and nephritis (0.1%).
Are there any important drug interactions I should be aware of?
Recommend minimizing systemic immunosuppression while receiving avelumab.
How do I adjust the dose in the setting of renal or hepatic insufficiency?
There are no necessary dose adjustments in the setting of pre-existing renal or hepatic insufficiency. If hepatotoxicity or nephrotoxicity develops during treatment with avelumab, treatment should be held and corticosteroid therapy considered for management of autoimmune hepatitis or nephritis.
Practical tips
* Despite premedications, severe or life-threatening infusion reactions to avelumab may occur. The infusion should be interrupted or slowed for mild to moderate infusion-related reactions. The infusion should be stopped and permanently discontinued for patients with grade 3 or 4 infusion reactions.
* Patients should have hepatic function, renal function, and thyroid function tests monitored throughout therapy.
What should my patients know about avelumab?
All patients should be educated on the side effects of avelumab including immune-mediated adverse events.
Patients should contact their health care provider if they experience any of the following:
* Rash
* Diarrhea
* Changes in caliber or color of stool
* Fever
* Excessive thirst
What else should I know about avelumab?
Avelumab was FDA-approved for both indications under accelerated approval based on tumor response rate and duration of response. Confirmatory trials are needed for verification and description of clinical benefit for continued FDA approval.
What useful links are available regarding avelumab?
* http://www.bavencio.com
* http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm547965.htm
Any ongoing clinical trials related to avelumab?
Clinical trials with avelumab are being conducted in several settings including those involving upfront therapy for glioblastoma multiforme, and palliative treatment as a single agent or in combination with chemotherapy in multiple solid tumor types. More information is available about the clinical trials at https://clinicaltrials.gov.
SARA K. BUTLER, PHARMD, BCPS, BCOP, is Clinical Oncology Pharmacy Supervisor, Barnes-Jewish Hospital, St. Louis, Mo., and also serves as a Pharmacy Forum column co-editor. RAMASWAMY GOVINDAN, MD, Co-Director, Section of Medical Oncology, Professor of Medicine, Washington University School of Medicine, Alvin J. Siteman Cancer Center, serves as the Pharmacy Forum column physician advisor. JANELLE E. MANN, PHARMD, BCOP, is an Investigational Drug Pharmacist, Washington University School of Medicine, Alvin J. Siteman Cancer Center, St. Louis, Mo., and serves as the Pharmacy Forum column co-editor.