Durvalumab (Imfinzi™)

What is durvalumab? Durvalumab is a human immunoglobulin G1 kappa monoclonal antibody that blocks PD-L1. How does durvalumab work? PD-L1 is frequently expressed on tumor cells and tumor-infiltrating immune cells. The binding of PD-L1 to PD-1 and CD80 (B7.1) inhibits T-cell activation and proliferation, resulting in T-cell exhaustion. Durvalumab binds to PD-L1 and blocks the interaction of PD-L1 to PD-1 and CD80 (B7.1), allowing heightened T-cell antitumor activity. What is this approved for? Durvalumab is approved for the treatment of locally advanced or metastatic urothelial carcinoma patients who have disease progression following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with a platinum-containing regimen. What is the basis for this approval? Durvalumab received FDA approval in May 2017 based on the results of an ongoing phase I/II open-label study. One hundred eighty-two stage IV, platinum-experienced urothelial carcinoma patients received durvalumab 10 mg/kg intravenously every 2 weeks for 12 months or until unacceptable toxicity or progressive disease. The primary endpoints were safety and confirmed objective response rate (ORR). The median age was 67 years and 71 percent were male. The ORR was 17.6 percent (95% CI, 12.3-23.9). Complete responses occurred in six patients (3.3%). Patients with PD-L1 high expression (≥ 25% of tumor or immune cells stained for PD-L1) had higher ORR when compared to patients with PD-L1 low or negative expression (27.4% to 4.1%, respectively). Seventy-five percent of responses were ongoing at the time of data cutoff and occurred early in the course of therapy. Duration of response was not reached (range, ≥ 0.9 to ≥ 19.9 months) (JAMA Oncol 2017;3(9):e172411). How do you administer this drug? Durvalumab is administered as an IV infusion diluted in 0.9 percent sodium chloride for injection, USP or 5 percent dextrose injection, USP to a final concentration of 1 to 15 mg/mL. It is given over 60 minutes via 0.2 or 0.22 micron in-line filter. Are there any pre-medications needed? None required. What are the common side effects associated with durvalumab (> or =10%)? The most common toxicities include fatigue, musculoskeletal pain, constipation, decreased appetite, nausea, urinary tract infection, peripheral edema, abdominal pain, fever, diarrhea/colitis, dyspnea, rash, and cough. What are the uncommon side effects associated with durvalumab (less than 10%)? Immune-mediated toxicities including the following may occur with durvalumab: pneumonitis, hepatitis, hypothyroidism, hyperthyroidism, adrenal insufficiency, diabetes mellitus, and nephritis. Infections including sepsis may occur in ~30 percent of patients. Approximately 2 percent will develop an infusion reaction. Are there any important drug interactions I should be aware of? No known drug interactions. How do I adjust the dose in the setting of renal or hepatic insufficiency? No dosage adjustment is needed in patients with mild or moderate renal insufficiency or mild hepatic insufficiency. Patients with severe renal impairment or moderate-to-severe hepatic impairment were not included in durvalumab clinical trials. Practical tips Clinically significant immune-related adverse events including rash, diarrhea/colitis, hepatitis, pneumonitis, and hypophysitis have been observed in patients receiving durvalumab. Patients should be educated to recognize and report symptoms to their health care team to determine if corticosteroids should be initiated to mediate toxicity. What should my patients know about durvalumab? Patients should contact their health care provider if they experience any of the following: New or worsening cough, shortness of breath, or chest pain Yellowing of the skin or whites of your eyes Dark colored urine or black, tarry stools Headaches Extreme tiredness Decrease in the amount of urine, frequent urination, or pain when urinating Fever or flu-like symptoms Swelling of the face or ankles Skin blistering What else should I know about durvalumab? Patients with autoimmune disease, irritable bowel disease, untreated CNS metastases, those with previous exposure to anti-PD-1 or anti-PD-L1 therapies, or those who require greater than 10 mg/day prednisone equivalents were excluded from durvalumab clinical trials (J Clin Oncol 2016;34(26):3119-3125). What useful links are available regarding durvalumab? https://www.imfinzi.com/ https://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm555930.htm Any ongoing clinical trials related to durvalumab? Clinical trials with durvalumab as monotherapy and in combination with chemotherapy and biotherapy (particularly with tremelimumab, a cytotoxic T-lymphocyte antigen-4 monoclonal antibody) are being conducted in lung cancer, head and neck cancers, pancreatic adenocarcinoma, and other advanced hematologic and oncologic malignancies. More information is available about these clinical trials at https://clinicaltrials.gov. HEIDI D. FINNES, PHARMD, BCOP, is Senior Manager, Pharmacy Cancer Research, and Assistant Professor of Pharmacy, College of Medicine at the Mayo Clinic, Rochester, Minn. 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. 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. 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.Heidi D. Finnes, PharmD, BCOP: Heidi D. Finnes, PharmD, BCOPRamaswamy Govindan, MD: Ramaswamy Govindan, MD