In cooperation with the Food and Drug Administration (FDA), and as a service to our members, SITC will periodically distribute information about newly approved therapies for cancer patients. This helps FDA inform oncologists and professionals in oncology-related fields of recent approvals in a timely manner. Included in the email from the FDA will be a link to the product label, which will provide the relevant clinical information on the indication, contraindications, dosing, and safety. In sending this information, SITC does not endorse any product or therapy and does not take any position on the safety or efficacy of the product or therapy described. The following is a message from the Director of the FDA Oncology Center of Excellence, Dr. Richard Pazdur:
On December 18, 2019, the U.S. Food and Drug Administration granted accelerated approval to Padcev (enfortumab vedotin-ejfv), a Nectin-4-directed antibody and microtubule inhibitor conjugate, meaning the drug specifically targets cancer cells – in this case, the cell adhesion molecule Nectin-4, which is highly expressed in urothelial cancers. Padcev is indicated for the treatment of adult patients with locally advanced (when cancer has grown too large to be surgically removed) or metastatic (when cancer cells spread to other parts of the body) urothelial cancer who have previously received a programmed death receptor-1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitor and a platinum-containing chemotherapy. Platinum-containing chemotherapy, PD-1 and PD-L1 inhibitors are standard treatments for patients with bladder cancer, the sixth most common cancer in the U.S. Urothelial cancer, accounting for more than 90% of bladder cancers, begins in cells that line the bladder and nearby organs. Padcev represents a new type of therapy for patients with advanced urothelial cancer whose disease has progressed on chemotherapy and immunotherapy.
“Antibody-drug conjugates are strategic tools in the targeted treatment of cancer. These conjugates combine the ability of monoclonal antibodies to target specific receptors on cancer cells and then deliver a drug to the cancer cell,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. “Padcev is an antibody-drug conjugate that targets Nectin-4, a cell surface protein expressed on bladder cancer cells and a cell-killing agent, monomethyl auristantin E.”
Padcev was approved based on the results of a clinical trial that enrolled 125 patients with locally advanced or metastatic urothelial cancer who received prior treatment with a PD-1 or PD-L1 inhibitor and platinum-based chemotherapy. The overall response rate, reflecting the percentage of patients who had a certain amount of tumor shrinkage, was 44%, with 12% having a complete response and 32% having a partial response. The median duration of response was 7.6 months.
The most common side effects for patients taking Padcev were fatigue, peripheral neuropathy (nerve damage resulting in tingling or numbness), decreased appetite, rash, alopecia (hair loss), nausea, altered taste, diarrhea, dry eye, pruritis (itching) and dry skin. Patients may experience hyperglycemia (high blood sugar levels) regardless of whether they have diabetes or not, and blood sugar levels should be monitored closely in patients receiving Padcev. Patients should also be monitored for new or worsening peripheral neuropathy and have the dose of Padcev interrupted, reduced or discontinued if needed. Patients may experience eye disorders, including dry eyes and vision changes, while taking Padcev. Health care professionals may consider prophylactic artificial tears for dry eyes and referral to an ophthalmologist for any new symptoms related to the eye. Patients who experience infusion site extravasation (leakage of medications administered through veins into the surrounding tissue) may experience delayed extravasation site reactions with pain, blisters and peeling of skin. Adequate venous access should be ensured prior to starting Padcev.
The FDA advises health care professionals to tell patients of reproductive age to use effective contraception during treatment with Padcev, and for a period of time thereafter. Women who are pregnant or breastfeeding should not take Padcev because it may cause harm to a developing fetus or newborn baby, or cause delivery complications.
Padcev was granted Accelerated Approval, which enables the FDA to approve drugs for serious conditions to fill an unmet medical need based on a result that is reasonably likely to predict a clinical benefit to patients. A further clinical trial is required to verify and describe Padcev’s clinical benefit.
The FDA granted this application Priority Review and Breakthrough Therapy designation, which expedites the development and review of drugs that are intended to treat a serious disease or condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapies. Padcev received approval approximately three months before the goal date.
The FDA granted the approval of Padcev to Astellas Pharma US Inc.