Padcev drug under compassionate use? Anyone heard of this?

[StephH72]

Hi. Asking for a friend whose husband has advanced PC and has run out of standard of care options. Oncologist just got approval for PadCev under compassionate use. Anyone heard of this drug?

[DrawingSnowmen]

Here's some info:

ascopubs.org/doi/10.1200/JC...

It's in phase 2 trials for mCRPC, currently approved for bladder cancer.

[NotDFL]

Currently being tested in a phase 2 trial. Early results reported in an abstract at the 2024 ASCO meeting:

ascopubs.org/doi/pdf/10.120...

[j-o-h-n]

From Sir A & Madam i

Padcev (generic name: enfortumab vedotin-ejfv) is an FDA-approved medication used for the treatment of certain types of cancer. Specifically, it is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma, which is a common type of bladder cancer. Padcev is typically prescribed for patients who have previously received treatment with a PD-1 or PD-L1 inhibitor and a platinum-containing chemotherapy.

Mechanism of Action

Padcev is an antibody-drug conjugate (ADC) that works by combining a monoclonal antibody with a cytotoxic (cell-killing) agent. Here's how it functions:

Targeting Cancer Cells: The monoclonal antibody component of Padcev specifically targets Nectin-4, a protein that is commonly expressed on the surface of urothelial carcinoma cells.

Delivery of Cytotoxic Agent: Once Padcev binds to the cancer cell, it is internalized into the cell.

Releasing the Cytotoxic Agent: Inside the cancer cell, the cytotoxic agent (monomethyl auristatin E, or MMAE) is released, which then disrupts the microtubule network essential for cell division.

Cell Death: The disruption of microtubules leads to cell cycle arrest and apoptosis (programmed cell death), effectively killing the cancer cells.

Indications

Padcev is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have:

Previously received a PD-1 or PD-L1 inhibitor.

Previously received platinum-containing chemotherapy.

Administration

Padcev is administered via intravenous (IV) infusion. The typical dosing schedule is:

1.25 mg/kg (up to a maximum of 125 mg) administered as an IV infusion over 30 minutes on Days 1, 8, and 15 of a 28-day cycle.

The treatment continues until disease progression or unacceptable toxicity.

Side Effects

Like all medications, Padcev can cause side effects. Common side effects include:

Fatigue

Peripheral neuropathy (numbness, tingling, or pain in the hands and feet)

Rash

Elevated liver enzymes

Decreased appetite

Nausea and vomiting

Diarrhea

More serious side effects can occur, including:

Severe skin reactions: Including Stevens-Johnson syndrome and toxic epidermal necrolysis.

Peripheral neuropathy: Severe and debilitating.

Ocular disorders: Including dry eye and vision changes.

Hyperglycemia: Particularly in patients with pre-existing diabetes or those receiving corticosteroids.

Infusion site reactions

Monitoring and Precautions

Patients receiving Padcev should be monitored regularly for:

Signs of neuropathy.

Liver function tests.

Blood glucose levels.

Signs of skin reactions.

Conclusion

Padcev represents an important treatment option for patients with advanced urothelial carcinoma, particularly for those who have exhausted other lines of therapy. Its targeted mechanism allows it to deliver cytotoxic agents directly to cancer cells, minimizing damage to normal cells. However, its use comes with the potential for significant side effects, and it requires careful monitoring by healthcare professionals. Always consult with an oncologist or healthcare provider for personalized medical advice and treatment plans.

Good Luck, Good Health and Good Humor.

j-o-h-n