Bladder cancer is one of the most prevalent cancers of the urinary system worldwide. According to the World Health Organization (WHO), about 570,000 new cases of bladder cancer were reported worldwide in 2020, of which some 210,000 resulted in death. These statistics suggest that bladder cancer is one of the leading cancers that occurs frequently in men and women.

For metastatic bladder cancer, the five-year survival rate is relatively low at 5-15 percent, with most patients dying within two years. For advanced bladder cancer, there is no standard treatment for patients whose cancer has progressed or recurred after treatment with immuno-oncology drugs and platinum-based chemotherapy agents. In recent years, however, innovative therapies, including antibody-drug conjugates (ADCs), have been developed to overcome these limitations.

What is an antibody-drug conjugate (ADC)?

An antibody-drug conjugate (ADC) is a combination drug that combines a monoclonal antibody that recognizes a specific protein on the surface of cancer cells with a potent anticancer drug linked to the antibody. The monoclonal antibody targets and selectively binds to specific antigens on the surface of cancer cells, and the linked anticancer drug is delivered inside the cancer cell, where it exerts cytotoxicity and destroys the cancer cell. This mechanism allows for an effective attack on cancer cells while minimizing damage to normal cells.

About Enfortumab Vedotin

Enfortumab Vedotin is one of a class of ADCs developed to treat bladder cancer, specifically metastatic urothelial carcinoma. Urothelial carcinoma is the most common type of bladder cancer, accounting for about 91 percent of all bladder cancers, and is most common in older adults, with eight out of 10 patients over 60, and is frequently recurrent and metastatic. Metastatic bladder cancer is deadly, with a five-year survival rate of only about 5 percent.

Enfortumab Vedotin targets a protein called Nectin-4. Nectin-4 is overexpressed on the surface of bladder cancer cells, and when the antibody in Enfortumab Vedotin recognizes and binds to it, it enables selective cancer cell attack. The anticancer drug monomethyl auristatin E (MMAE) is then delivered inside the cancer cells, inhibiting intracellular microtubules to block cancer cell growth and proliferation.

How Enfortumab Vedotin works

1. Recognition of a specific target: The antibody in Enfortumab Vedotin recognizes and binds with high affinity to the Nectin-4 protein on the surface of bladder cancer cells.

2. Anticancer drug delivery: The bound antibody-drug complex enters the cancer cell by endocytosis through the cell membrane.

3. Destruction of cancer cells: Inside the cancer cell, the complex is degraded, and the MMAE released during this process destroys intracellular microtubules, causing cell cycle arrest and inducing apoptosis.

Clinical trials and efficacy

Enfortumab Vedotin has been studied in various clinical trials to demonstrate its efficacy and safety. In the EV-201 trial, 44 percent of treated patients achieved a clinically significant reduction in tumor size, with 12 percent achieving complete remission. In the EV-301 trial, patients receiving Enfortumab Vedotin had a significantly longer median survival of 12.88 months and improved overall survival compared to patients receiving conventional chemotherapy.

Benefits and limitations of Enfortumab Vedotin

One of the main advantages of Enfortumab Vedotin is its high selectivity for cancer cells. Because the drug targets the Nectin-4 protein and acts selectively on cancer cells, it minimizes damage to normal cells. This is a huge advantage as it allows for effective cancer treatment while maintaining the patient's quality of life.

Enfortumab Vedotin also has a high response rate in patients who have not responded to conventional treatments, making it a novel treatment option.

However, Enfortumab Vedotin does have limitations.

First, like all anticancer drugs, Enfortumab Vedotin can have side effects. The most commonly reported side effects include neurotoxicity, skin rash, and fatigue. These side effects must be managed during the patient's treatment, and ongoing research is needed to minimize side effects.

Second, the relatively high cost of treatment with Enfortumab Vedotin may limit access. This remains an important challenge in developing cost-effective treatment options.

Enfortumab Vedotin represents a new paradigm in urothelial cancer treatment

Enfortumab Vedotin offers an innovative approach to treating bladder cancer and is emerging as an effective treatment option, especially in metastatic urothelial cancer. By selectively attacking specific cancer cells, the drug may play an essential role in reducing side effects and improving patient survival compared to conventional therapies.

Urothelial carcinoma is a rapidly progressive disease that requires ongoing treatment. Still, until now, there has been no standard treatment, and chemotherapy agents have been used as an option after second-line treatment with immuno-oncology agents.

Enfortumab Vedotin is a treatment that can be used for patients whose cancer has progressed or recurred after chemotherapy (first-line treatment) and immuno-oncology (second-line or first-line maintenance therapy) and is expected to provide a new paradigm for treating patients with locally advanced or metastatic urothelial cancer.