Stage 4 Urothelial (Bladder and Urinary Tract) Cancers: Enfortumab Vedotin-Ejfv Receives FDA Approval

On 18 December 2019, the US Food and Drug Administration (FDA) granted accelerated approval for locally advanced or metastatic urothelial, bladder and urinary tract, cancers to enfortumab vedotin-ejfv (Padcev) accelerated approval. For this drug to be used in patients with urothelial cancer, they must previously have received anti-PD-1 or anti-PD-L1 immunotherapy and platinum chemotherapy in neoadjuvant / adjuvant or metastatic settings.

On 9 July 2021, Astellas announced regular approval and expanded indication: “As a single agent for adults with locally advanced or metastatic urothelial cancer unsuitable for cisplatin chemotherapy and previously receiving one or more treatments.” Conversion from accelerated to regular approval and expansion was influenced by phase-3 EV-301 results .

How Does Enfortumab Vedotin-Ejfv Work?

It is the first FDA-approved Nectin-4-targeted antibody–drug conjugate.

Enfortumab vedotin is a first-in-class conjugate targeting cell-surface Nectin-4, highly expressed in bladder cancer. Preclinical data suggest binding Nectin-4-expressing cells, followed by entry and release of a microtubule, cytoskeleton-disrupting antitumor agent, stops proliferation and triggers apoptosisbeing triggered (programmed cell death; see the figure above). Enfortumab vedotin is a drug that has been under development since 2007 through a collaboration between Seattle Genetics and Astellas.

EV-201 Study

Previously PD-1 or PD-L1 inhibitor- and platinum-treated locally advanced or metastatic patients, totaling 125, participated in the single-arm multicenter EV-201 efficacy trial.

Within a 28-day period, on days 1, 8, and 15, patients received 1.25 mg / kg until progression or unacceptable toxicity. Main endpoints were objective response and duration.

• Complete and partial responses of % 12 and % 32 respectively produced overall response of % 44.
• Estimated median response duration was 7.6 months.
• In a group previously receiving at least 2 lines, % 12 achieving complete response is especially noteworthy.

The most common (≥% 20) adverse effectsincluded fatigue, peripheral neuropathy, reduced appetite, rash, alopecia, nausea, dysgeusia, altered taste, diarrhea, dry eyes, itching, and dry skin. Rare diabetic ketoacidosis and death occurred regardless of prior diabetes. Glucose should be closely monitored in patients with or at risk of diabetes or hyperglycemia.

Recommended enfortumab vedotin-ejfv doseis in a 28-day cycle on days 1, 8, and 15, as a 30-minute intravenous infusion, 1.25 mg / kg (maximum 125 mg), until progression or unacceptable toxicity.