Enfortumab Vedotin (Padcev) and Pembrolizumab (Keytruda) Regimen

Enfortumab vedotin (Padcev®) + pembrolizumab (Keytruda®) is used for urothelial cancers, particularly bladder cancer , combining “targeted therapy + immunotherapy.”

How Does Enfortumab Vedotin (Padcev®) + Pembrolizumab (Keytruda®) Work?

• Enfortumab vedotin targets a protein called Nectin-4 on bladder cancer cell surfaces.
• After binding, it enters the cell and releases MMAE , a chemical that stops cell growth and division.
• Pembrolizumab is an immunotherapy designed to block signals through which tumor cells suppress the immune system, allowing it to attack bladder cancer cells.

Goals of Enfortumab Vedotin (Padcev®) + Pembrolizumab (Keytruda®) Treatment

• The combination aims to shrink tumors and reduce urothelial cancer symptoms.
• It is generally not intended to provide a complete cure.

Enfortumab Vedotin and Pembrolizumab Combination

Together, the medicines directly target cancer cells and activate immunity. Enfortumab's targeted action and pembrolizumab's immune enhancement complement one another in metastatic bladder cancer.

Clinical Trials and Efficacy

• EV-103 (KEYNOTE-869) and EV-302 (KEYNOTE-A39) , phase 1b/2 and phase 3 trials, demonstrated a substantial survival advantage over chemotherapy with the combination.

• EV-302 Results:

  • Median overall survival: 31.5 months (chemotherapy: 16.1 months, P < 0.00001)

  • Disease-free survival: 12.5 months (chemotherapy: 6.3 months)

  • Objective response rate: 67.7% (complete response 29.1%)

  • The immunological response increased markedly, with particular benefit in patients with liver metastases in the study.

These findings led to FDA approval in December 2023 and adoption in national guidelinesregardless of cisplatin eligibility .

Treatment Schedule

Enfortumab Vedotin (IV Infusion)

• Days 1 and 8: Administered intravenously over 30 minutes.

Pembrolizumab (IV Infusion)

• Day 1: Administered intravenously over 30 minutes.

Estimated Total Infusion Time:

• Day 1 may require up to 1 hour in total.
• Day 8 may require approximately 30 minutes in total.

Treatment is generally given at an outpatient chemotherapy center , and patients may return home afterward.

Treatment repeats every 3 weeks (21 days), a period known as a cycle .
It continues until it stops working or intolerable side effects develop during treatment.

Side Effects

Safety data for EV + pembrolizumab identify the following very common effects (≥20%, approximately one in five patients or more):

• Skin rash, all grades (68%),
• Peripheral neuropathy (67%),
• Fatigue (51%),
• Itching (41%),
• Hair loss or alopecia (35%),
• Decreased appetite (33%),
• Diarrhea (38%),
• Weight loss (33%),
• Nausea (26%), and
• Constipation (26%).

Frequently reported laboratory abnormalities include increased liver enzymes (AST 75%, ALT 59%; severe in approximately 5%), creatinine (71%), and blood glucose (66%; severe hyperglycemia in 14%).

Severity varies between patients and may range from mild to serious. Some effects are managed by delaying treatment, reducing doses, or stopping permanently.

Some effects can be prevented with prophylactic medicines during treatment.

For much more detailed information, see our article Side Effects and Management of Enfortumab Vedotin–Pembrolizumab Combination Treatment for further guidance.

Follow-Up and Monitoring

Blood Tests: Testing may be performed before each treatment, generally including:

• Complete Blood Count
• Comprehensive Metabolic Panel

Imaging:

• Before and during treatment, imaging may include X-rays, MRI, CT, and PET scans as appropriate.
• These assess response or determine whether disease is progressing.

How Can Blood Tests and Imaging Results Affect Treatment Decisions?

• Your doctor may recommend continuing, reducing the dose, delaying treatment, or switching therapy.

Important Warnings

• Skin reactions such as rash and itching are common , generally appearing in the first month. Topical creams or ointments may help when mild.
• Blood glucose may rise, even without a history of diabetes.
• Eye problems may include dryness, blurred vision, watering, or redness. Contact your doctor if vision changes occur.
• Pembrolizumab may cause serious immune reactions.
  • The organs most often affected include: Lungs, bowel, liver, thyroid, kidneys, and pituitary gland
  • For serious immune reactions, corticosteroids such as prednisone may be given and treatment withheld.

Medicine-Specific Warnings

Enfortumab Vedotin (Padcev®)

• FDA Boxed Warning: Risk of serious skin reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).
• High blood glucose may require treatment interruption if uncontrolled.
• Eye disorders may occur.

Pembrolizumab (Keytruda®)

• Given by IV infusion.
• Serious infusion reactions may require interruption.
• Risk of lung inflammation (pneumonitis).
• Risk of bowel inflammation (colitis). Seek medical care for severe diarrhea, abdominal pain, or blood in stools.
• Liver inflammation (hepatitis) may develop.
• Endocrine gland inflammation may affect the adrenal, thyroid, or pituitary glands.

Pregnancy and Breastfeeding

• These medicines may cause serious harm during pregnancy.
• Female patients should use contraception during treatment and for 2 months after the last dose.
• Male patients should use effective contraception for 4 months.
• Breastfeeding is not recommended during treatment and for at least 3 weeks after the last dose.