Padcev Plus Keytruda Elicits Encouraging Results in Metastatic Bladder Cancer

More than half of patients with metastatic, cisplatin-ineligible bladder cancer saw their cancer shrink when given Padcev and Keytruda in a clinical trial.

Treatment with Padcev (enfortumab vedotin-ejfv) plus Keytruda (pembrolizumab) showed promising results for patients with unresectable locally advanced or metastatic bladder cancer that is ineligible for cisplatin-based chemotherapy, according to early findings from a subgroup of patients in the phase 1b/2 EV-103 clinical trial, also known as KEYNOTE-869.

“Approximately half of patients with advanced urothelial carcinoma are ineligible for cisplatin-based chemotherapy,” said Dr. Ahsan Arozullah, senior vice president and head of development therapeutic areas at Astellas, the manufacturer of Padcev, said in a press release. “We intend to discuss cohort K results with regulatory authorities as we seek to develop a new first-line treatment combination for these patients.”

READ MORE: Padcev Continues to Show Promise in Patients with Previously Treated Bladder Cancer

The patient subgroup, referred to as cohort K, met its goal of confirmed objective response rate (the percentage of patients whose tumors shrunk as a result of treatment), which was 64.5% for patients who received Padcev plus Keytruda. At the point of data collection, the average duration of response was not yet reached.

Researchers also plan on analyzing disease control rate and progression-free survival (time from treatment until disease worsens) in cohort K, which is made up of two groups: those who received Padcev plus Keytruda and those who received Padcev alone.

Padcev works by binding to Nectin-4, a protein that is often found on the surface of bladder cancer cells. Then, according to preclinical studies of Padcev, the drug releases a molecule into the cancer(?) that can result in the cell being unable to reproduce and die.

Conversely, Keytruda is an immunotherapy agent that works by blocking a protein called PD-1 on cell surfaces, thus helping the immune system to recognize and attack the tumors.

When given together in the EV-103 trial, Padcev and Keytruda resulted in severe (grade 3 or higher) side effects in more than 5% of patients.

The most common severe side effects were: rash; anemia (lack of healthy red blood cells to carry oxygen throughout the blood); increased levels of lipase, which could lead to pancreatic issues; urinary tract infection; high blood sugar; fatigue; low levels of neutrophils in the blood; blood in the urine (known as hematuria); diarrhea; acute or chronic kidney injury; low levels of blood sodium; weight loss; fainting; decreased phosphate levels in the blood; lung inflammation sepsis; and increased alanine aminotransferase, which could lead to liver issues.

Updated results from cohort K of the EV-103 trial will be presented at an upcoming medical conference, according to the release.


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