Padcev (enfortumab vedotin) Treatment for Bladder Cancer

Padcev is the first approved treatment option for patients with advanced bladder cancer failing standard chemotherapy and immune treatments. Recent trial results further suggest that Padcev (enfortumab vedotin) combined with immunotherapy is more effective than chemotherapy when used as first line treatment for patients with locally advanced or metastatic urothelial (bladder) cancer.^1-7

About Padcev (Enfortumab Vedotin)

Padcev is a novel precision cancer medicine known as an antibody drug conjugate, a type of therapy that combines an antibody that targets a specific protein on the surface of tumor cells with a payload of powerful chemotherapy. It is composed of an anti-Nectin-4 monoclonal antibody attached to a microtubule-disrupting agent, MMAE. Enfortumab vedotin targets Nectin-4, a cell adhesion molecule identified as an ADC target which is expressed on many solid tumors. This antibody is chemically linked with an agent that penetrates the tumor cell and destroys its structure.

Padcev was initially approved by the U.S. Food and Drug Administration in December 2019 for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and a platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery or in a locally advanced or metastatic setting. The FDA expanded the approval to include Padcev in combination with Keytruda immunotherapy. 

What does the data show?

In the original multi-institutional clinical trial Padcev produced responses in 44% of patients with locally advanced or metastatic urothelial cancer who had been previously treated with chemotherapy and checkpoint inhibitors. Among 125 patients who had received both standard chemotherapy plus a checkpoint inhibitor 12% had a complete response with no detectable sign of cancer and the median overall survival was 12 months. Notably, 38% of people whose cancer had spread to the liver responded to the treatment.

Padcev Superior to Chemotherapy in Advanced Urothelial Cancers

Padcev also outperformed chemotherapy on key survival metrics in a phase 3 clinical trial, extending the life of patients with previously treated advanced urothelial cancer by nearly four months, compared with standard of care.

Platinum-containing chemotherapy sequenced with programmed cell death protein-1/programmed death ligand 1 (PD-1/L1) inhibitors is the standard of care for patients with locally advanced or metastatic urothelial carcinoma.

The EV-301 Trial – EV-301 was a phase 3 clinical trial designed to evaluate Padcev versus physician’s choice of chemotherapy (docetaxel, paclitaxel or vinflunine) in approximately 600 patients with locally advanced or metastatic urothelial cancer who were previously treated with a PD-1 or PD-L1 inhibitor and platinum-based therapies. In September 2020 the phase 3 trial met its primary endpoint of improving overall survival compared to chemotherapy. Padcev significantly delayed cancer progression and improved overall survival with a 30 percent reduction in risk of death.⁴

Padcev treated patients more likely to respond to treatment and experience delayed cancer progression-free survival. Most importantly overall survival improved with Enfortumab; 12.9 months, which as 3.9 months longer than what was seen in patients treated with chemotherapy.

The most common side effects for patients taking Padcev were fatigue, peripheral neuropathy decreased appetite, rash, hair loss, nausea, altered taste, diarrhea, dry eye, itching and dry skin.

Padcev® + Keytruda® Receives FDA Approval for Locally Advanced Urothelial Cancer

The FDA has granted accelerated approval to Padcev in combination with Keytruda for patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy.

The approval was supported by the KEYNOTE-869 clinical trial that demonstrated a 68% overall response rated with 12% of patients achieving a complete remission with an average response duration exceeding 22 months in patients with locally advanced or metastatic urothelial cancer who were not eligible to receive cisplatin-based chemotherapy.

Further supporting data comes from the EV-302 clinical 2 trial which compared Padcev plus Keytruda (EVP) to chemotherapy in 886 patients with previously untreated locally advanced or metastatic urothelial carcinoma. The EVP treated patients survived twice as long without cancer progression and the average survival duration was 31 months compared to 16 months with chemotherapy.⁷

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Connect With Others for Support and information

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References:

1. Seattle Genetics and Astellas Receive FDA Breakthrough Therapy Designation for Enfortumab Vedotin in Locally Advanced or Metastatic Urothelial Cancer
2. abstracts.asco.org/239/AbstView_239_265881.html
3. FDA approves new type of therapy to treat advanced urothelial cancer

4. FDA grants accelerated approval to enfortumab vedotin-ejfv with pembrolizumab for locally advanced or metastatic urothelial carcinoma. FDA. April 3, 2023. Accessed April 3, 2023. https://www.fda.gov/drugs/resources-information-approved-drugss

5. Enfortumab vedotin-ejfv. Prescribing information. Seagen Inc. Updated April 2023. Accessed April 3, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761137s018.pdf

6. FDA grants approval for Padcev (enfortumab vedotin-ejfv) with Keytruda (pembrolizumab) for first-line treatment of locally advanced or metastatic urothelial cancer. News release. Seagen, Inc. and Astellas Pharma, Inc. April 3, 2023. Accessed April 3, 2023. https://investor.seagen.com/press-releases/news-details/2023

7. Powles TB, Perez Valderrama B, Gupta S, et al. EV-302/KEYNOTE-A39: Open-label, randomized phase III study of enfortumab vedotin in combination with pembrolizumab (EV+P) vs chemotherapy (Chemo) in previously untreated locally advanced metastatic urothelial carcinoma (la/mUC). Presented at: ESMO Congress 2023; October 20-24, 2023; Madrid, Spain. Abstract LBA6.