ENFORTUMAB VEDOTIN
Background and Date of Approval
Enfortumab vedotin-ejfv, marketed as Padcev, is an antibody-drug conjugate (ADC) designed to target Nectin-4, a protein highly expressed in urothelial carcinoma. The U.S. Food and Drug Administration (FDA) granted accelerated approval on December 18, 2019, for adult patients with locally advanced or metastatic urothelial cancer who had previously received a PD-1 or PD-L1 inhibitor and platinum-containing chemotherapy. This approval was supported by clinical trials demonstrating efficacy in this patient population. Subsequent studies, including the EV-301 trial, have provided further evidence of clinical benefit.
Uses
Treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a PD-1 or PD-L1 inhibitor and platinum-containing chemotherapy.
How is it administered?
The recommended dosage is 1.25 mg/kg (up to a maximum of 125 mg) administered intravenously over 30 minutes on Days 1, 8, and 15 of a 28-day cycle. Treatment continues until disease progression or unacceptable toxicity occurs.
Side Effects
Serious Side Effects: Severe Peripheral Neuropathy: May necessitate dose modification or discontinuation.â Serious Skin Reactions: Including Stevens-Johnson syndrome and toxic epidermal necrolysis; discontinue treatment if these occur.â Hyperglycemia: Can lead to ketoacidosis or hyperosmolar hyperglycemic state; monitor and manage appropriately.â Common Side Effects: Fatigue Nausea Decreased Appetite Diarrhea Rash Alopecia Dysgeusia (altered taste) Dry Eyes
Warnings
Peripheral Neuropathy: Monitor patients for symptoms such as numbness or tingling in the hands and feet.â Ocular Disorders: Patients may experience dry eyes or blurred vision; regular ophthalmologic evaluations are recommended.â Hyperglycemia: Monitor blood glucose levels, especially in patients with diabetes or risk factors for hyperglycemia.â Infusion Site Reactions: Observe for redness, swelling, or discomfort at the infusion site during and after administration.â Embryo-Fetal Toxicity: Advise pregnant women of the potential risk to the fetus and recommend effective contraception during treatment.
Precautions
Before initiating therapy, assess patients for pre-existing peripheral neuropathy and monitor for new or worsening symptoms during treatment. Patients with a history of hyperglycemia should have their blood glucose levels closely monitored. Advise patients to use artificial tears or other lubricating ophthalmic treatments to alleviate dry eyes. Women of childbearing potential should use effective contraception during treatment and for at least two months after the final dose.
Word of Advice
Patients with conditions treated by enfortumab vedotin should report promptly any new or worsening symptoms, particularly those affecting nerve function, skin reactions, or blood glucose levels. Regular communication with healthcare providers enables timely management of adverse effects. Adherence to scheduled appointments and monitoring protocols remains essential for safe and effective treatment.
References
https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-enfortumab-vedotin-ejfv-metastatic-urothelial-cancer https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761137s019lbl.pdf https://fda.report/DailyMed/b5631d3e-4604-4363-8f20-11dfc5a4a8ed https://www.padcev.com/about-padcev
Frequently Asked Questions
What is the use of enfortumab vedotin?
Enfortumab vedotin, marketed under the brand name Padcev, is primarily used to treat adults with locally advanced or metastatic urothelial carcinoma, which is the most common type of bladder cancer. It is typically prescribed for patients who have previously received a PD-1 or PD-L1 inhibitor and platinum-containing chemotherapy. Additionally, enfortumab vedotin may be used in combination with pembrolizumab for patients ineligible for cisplatin-containing chemotherapy.
Is enfortumab vedotin chemotherapy or immunotherapy?
Enfortumab vedotin is classified as an antibody-drug conjugate (ADC), which is a form of targeted cancer therapy. It combines a monoclonal antibody that specifically targets Nectin-4âa protein highly expressed in urothelial cancer cellsâwith a cytotoxic agent that disrupts cancer cell division. This mechanism allows it to deliver chemotherapy directly to cancer cells while sparing healthy tissues. Therefore, enfortumab vedotin is distinct from traditional chemotherapy and immunotherapy, representing a hybrid approach that leverages aspects of both treatment modalities.
What is the success rate of enfortumab vedotin?
The effectiveness of enfortumab vedotin has been demonstrated in clinical trials. In a pivotal study, enfortumab vedotin achieved an overall response rate (ORR) of 44%, with 12% of patients experiencing a complete response and 32% showing a partial response. The median duration of response was 7.6 months. Furthermore, when combined with pembrolizumab, the ORR increased to approximately 67-68%, with notable improvements in progression-free and overall survival compared to traditional chemotherapy.
How much does enfortumab vedotin cost?
The cost of enfortumab vedotin can vary based on dosage, treatment duration, and insurance coverage. In the United States, the price for a 20 mg vial of Padcev is approximately Rs. 1,00,000, with a 30 mg vial costing around Rs. 1,55,000. Given that treatment involves multiple vials per dose, the total expense can be substantial. Patients are encouraged to consult with their healthcare providers and insurance companies to understand their financial responsibilities. Additionally, the manufacturer offers assistance programs to help eligible patients manage treatment costs.