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Transformative Evidence

EV-302: Enfortumab Vedotin and Pembrolizumab vs. Chemotherapy Alone in Untreated Locally Advanced or Metastatic Urothelial Cancer

Curated by Clinicians: Educational Forum with Videos, Abstracts and Conference Information
Videos

EV-302 Discussion Videos

Conference Coverage
Conference Highlights Written by Physician-Scientist
Presented by Thomas B. Powles, MBBS, MRCP, MD
(UroToday.com) The 2024 European Society of Medical Oncology (ESMO) Annual Congress held in Barcelona, Spain was host to the session Mini oral session: GU tumours, non-prostate. Dr. Thomas B. Powles presented an exploratory analysis of Nectin-4 Expression and Response to first line Enfortumab Vedotin (EV) + Pembrolizumab (P) in previously Untreated patients with locally advanced or metastatic urothelial cancer (UC).
Presented by Andrea B. Apolo, MD
(UroToday.com) The 2024 Bladder Cancer Advocacy Network (BCAN) Bladder Cancer Think Tank held in San Diego, CA was host to an implementation science session that addressed bridging evidence generation to practice in bladder cancer care. Dr. Andrea Apolo discussed the latest advances in the field of advanced urothelial carcinoma, focusing on the recently published phase III trials, EV-302 (enfortumab vedotin + pembrolizumab)1 and CheckMate 901 (nivolumab + gemcitabine/cisplatin)
Presented by Samuel U. Takvorian, MD, MS
(UroToday.com) The 2024 American Society of Clinical Oncology (ASCO) annual meeting featured a session on urothelial carcinoma, and a discussant presentation titled “Tailoring Treatment and Navigating Patient Preferences” by Dr. Samuel Takvorian discussing three abstracts.
Presented by Daniel P. Petrylak, MD
(UroToday.com) The 2024 American Society of Clinical Oncology (ASCO) annual meeting featured an oral abstract session on urothelial carcinoma, and a presentation by Dr. Daniel Petrylak discussing the impact of exposure on outcomes with enfortumab vedotin in patients with locally advanced or metastatic urothelial cancer. Enfortumab vedotin is approved in combination with pembrolizumab (EV-3021) and as a monotherapy for locally advanced or metastatic urothelial cancer based on the pivotal EV-2012 and EV-3013 trials.
Presented by Jens Bedke, MD
The 2024 ASCO annual meeting was host to a presentation by Dr. Jens Bedke who presented their poster titled: Enfortumab vedotin (EV) with pembrolizumab (P) versus chemotherapy in previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC): Analysis of cisplatin (cis)-eligible population from EV-302/KEYNOTE-A39.
Presented by Jonathan Rosenberg, MD
(UroToday.com) The 2024 American Urological Association (AUA) annual meeting held in San Antonio, TX was host to the Society of Urologic Oncology (SUO) session Dr. Jonathan Rosenberg discussed how to incorporate Enfortumab with or without Pembrolizumab into clinical practice.
Presented by Chiara Mercinelli, MD, Shilpa Gupta, MD, and Karima Oualla, MD, MSc
(UroToday.com) The 2024 American Urological Association (AUA) annual meeting held in San Antonio, TX was host to the AUA-IBCG Bladder Cancer Forum. Drs. Chiara Mercinelli, Shilpa Gupta, and Karima Oualla discussed the first line therapy for locally advanced or metastatic urothelial carcinoma in 2024.
Presented by Andrea Necchi, MD
(UroToday.com) The 2024 European Association of Urology (EAU) annual meeting featured a plenary session on living with advanced kidney cancer and urothelial cancer, and a state of the art lecture by Dr. Andrea Necchi discussing whether there is a new standard treatment of metastatic bladder cancer based on EV-302/KEYNOTE-A39.
Presented by Parminder Singh, MD
The 2024 American Society of Clinical Oncology Genitourinary (ASCO GU) cancers symposium held in San Francisco, CA between January 25th and 27th was host to a urothelial carcinoma oral abstract session. Dr. Parminder Singh delivered the discussant session for the two previously presented abstracts.
Presented by Michiel Simon van der Heijden, MD, PhD
Dr. Michiel van der Heijden presented subgroup analyses from EV-302, a phase 3 global trial of enfortumab vedotin in combination with pembrolizumab versus chemotherapy in previously untreated locally advanced metastatic urothelial carcinoma.
Presented by Andrea B. Apolo, MD

Dr. Andrea Apolo delivered the discussant for the preceding two late-breaking oral abstract presentations: EV-302/KEYNOTE-A39: Open-Label, Randomized Phase 3 Study of Enfortumab Vedotin in Combination with Pembrolizumab (EV+P) Vs Chemotherapy (Chemo) in Previously Untreated Locally Advanced Metastatic Urothelial Carcinoma (la/mUC), Nivolumab plus gemcitabine-cisplatin versus gemcitabine-cisplatin alone for previously untreated unresectable or metastatic urothelial carcinoma: results from the phase 3 CheckMate 901 trial

 

Presented by Thomas Powles, MD, MBBS, MRCP
Dr. Thomas Powles presented the late-breaking abstract results of EV-302/KEYNOTE-A39, an open label, randomized phase III study of enfortumab vedotin plus pembrolizumab versus chemotherapy in patients with previously untreated locally advanced and/or metastatic urothelial carcinoma.
Reno, Nevada (UroToday.com) -- Seagen Inc. and Astellas Pharma Inc. announced results from the Phase 3 EV-302 clinical trial (also known as KEYNOTE-A39) for PADCEV® (enfortumab vedotin-ejfv) in combination with KEYTRUDA® (pembrolizumab) versus chemotherapy. The combination improved overall survival (OS) and progression-free survival (PFS) with statistically significant and clinically meaningful results in patients with previously untreated locally advanced or metastatic urothelial cancer (la/mUC).
Presented by Michiel Simon Van Der Heijden MD, PhD
On the second day of the American Society for Clinical Oncology (ASCO) Genitourinary Cancer Symposium 2022 focused on urothelial carcinoma during the Trials in Progress Poster Session B, Dr. Van Der Heijden presented the rationale and design of EV-302 assessing enfortumab vedotin (EV) with pembrolizumab compared to chemotherapy as first-line treatment in advanced urothelial carcinoma (aUC).
Presented by Michiel S. van der Heijden, MD, PhD
Platinum-based chemotherapy is the mainstay of first-line treatment for medically eligible patients with advanced urothelial carcinoma (UC). Unfortunately, up to 50% of patients are unable to receive cisplatin, and disease progression often develops even for patients who receive cisplatin.
Physician-Scientist Review Articles
State of the Evidence Review Articles
July 2, 2024
Thank you for visiting UroToday’s Center of Excellence for Advanced Bladder Cancer (aUC). I am delighted to serve as its new editor. This Center of Excellence curates evergreen content on emerging diagnostic and treatment information in a rapidly changing field. Locally advanced and metastatic urothelial cancer (aUC) is an aggressive disease, with estimated 5-year survival being only around 8%.1 We have seen tremendous advances in recent years, including the approval of immunotherapies, targeted therapies, and antibody-drug conjugates which can significantly extend survival and improve quality of life for patients with aUC.
Written by Zachary Klaassen, MD, MSc Associate Professor of Urology Urologic Oncologist Medical College of Georgia, Georgia Cancer Center Augusta, GA and Rashid Sayyid, MD, MSc Urologic Oncology Fellow University of Toronto Toronto, Ontario, Canada
March 13, 2024

Introduction

Metastatic urothelial carcinoma is associated with a poor prognosis, with an estimated 17,000 deaths annually in the United States from this disease.1 Platinum-based chemotherapy had long been considered the standard of care first line treatment for platinum-eligible patients with metastatic urothelial carcinoma.
Physician-Scientist Commentaries
Peer-reviewed Abstract Supplemental Commentaries
Written by Salvador Jaime-Casas, MD, Abhishek Tripathi, MD, Sumanta K Pal, MD, and Wesley Yip, MD
This review highlights the genomic and molecular characterization advances recently made in upper tract urothelial carcinoma (UTUC) research. As we discussed, UTUC possesses distinctive molecular and genomic signatures, warranting its consideration as an independent entity. This aggressive malignancy is characterized by significant diagnostic challenges, often leading to pathological understaging or overtreatment.
Written by Gal Saffati, MD and David E. Hinojosa-Gonzalez, MD
Metastatic urothelial carcinoma (mUC) is a challenging disease with historically limited treatment options and poor survival outcomes. The introduction of immune checkpoint inhibitors (ICIs) and antibody-drug conjugates has revolutionized the treatment landscape, offering new hope for improved patient outcomes.
Written by Isadora Mamede, and Carlos Stecca
Bladder cancer ranks as the tenth most common cancer globally, with urothelial carcinoma comprising approximately 90% of cases. For decades, platinum-based chemotherapy (CTX) has been the mainstay of treatment, with cisplatin being preferred over carboplatin whenever possible.
Written by Jun Gong, MD
Dr. Melissa Reimers and I had the distinct pleasure of contributing a podcast on practical considerations for patients with metastatic urothelial carcinoma (UC) receiving first-line platinum-based chemotherapy followed by avelumab maintenance as per the JAVELIN Bladder 100 phase 3 trial.
Written by Evangelia Vlachou, MD and Vivek Nimgaonkar, MD
Enfortumab vedotin (EV) is a nectin-4-directed antibody-drug conjugate used in the treatment of advanced urothelial cancer (UC). EV demonstrated a 15-month overall survival benefit in combination with pembrolizumab (P) versus traditional chemotherapy in the EV 302 study and was approved as first-line treatment for advanced UC.
Written by Jennifer W. Li, MD and Karie Runcie, MD
Oligometastatic and locally recurrent urothelial cancer are understudied topics where the optimal management plan has not been established. Oligometastatic cancer generally refers to a less aggressive metastatic cancer with limited spread of only a few lesions, however, there is no clear definition among urothelial cancers.
Publications
Peer-Reviewed Journal Abstracts

The EV-302 trial found that the combination of enfortumab vedotin (EV) with pembrolizumab significantly improved survival for patients with metastatic urothelial carcinoma (mUC). However, given the high cost of the drugs, there is a need to assess its value by considering both efficacy and cost.

Platinum-based chemotherapy has been the standard first-line (1L) treatment for advanced urothelial carcinoma (UC) for decades, based on the proven efficacy and established safety profiles of cisplatin- and carboplatin-based regimens.

Metastatic urothelial carcinoma (muC) has historically had few effective therapeutic options. Recently, immune checkpoint inhibitors (ICIs), were introduced as therapeutic options for cisplatin-ineligible patients, however, direct head-to-head trials comparing these treatments are lacking.

Platinum-based chemotherapy has been the cornerstone of first-line treatment for advanced urothelial carcinoma for decades, based on its proven efficacy and well-characterized safety profile. Although enfortumab vedotin (EV) plus pembrolizumab showed superior efficacy versus platinum-based chemotherapy in the EV-302 phase 3 trial,

The EV-302 study1 marks a pivotal leap in the management of advanced urothelial carcinoma, setting a new benchmark for frontline therapy. Enfortumab vedotin plus pembrolizumab is the first combination therapy that has ever outperformed standard chemotherapy.

Enfortumab vedotin (EV) is an antibody-drug conjugate approved alone and in combination with pembrolizumab for advanced urothelial cancer (UC). EV-related-cutaneous-events (EVCEs) are common and rarely life-threatening.

BACKGROUND No treatment has surpassed platinum-based chemotherapy in improving overall survival in patients with previously untreated locally advanced or metastatic urothelial carcinoma.
Press Releases
Official Announcements on Clinical Developments
  • First regimen approved in advanced urothelial cancer to demonstrate superiority to platinum-containing chemotherapy, the standard of care for nearly 40 years1
  • European Marketing Authorization based on positive overall survival and progression-free survival results from the global Phase 3 EV-302 trial1

Reno, Nevada (UroToday.com) -- Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, “Astellas”) announced that the European Commission has granted Marketing Authorization for PADCEVTM (enfortumab vedotin, an antibody-drug conjugate [ADC]) in combination with KEYTRUDA® (pembrolizumab, a PD-1 inhibitor) for the first-line treatment of adult patients with unresectable or metastatic urothelial cancer, who are eligible for platinum-containing chemotherapy.
PADCEV plus pembrolizumab approved based on groundbreaking EV-302 trial

Confirmatory trial found PADCEV plus pembrolizumab nearly doubled median overall survival compared to standard of care platinum-based chemotherapy

Reno, Nevada (UroToday.com) Pfizer Inc. and Astellas Pharma Inc. today announced that on December 15, 2023 the U.S. Food and Drug Administration (FDA) has approved PADCEV® (enfortumab vedotin-ejfv, an antibody-drug conjugate [ADC]) with KEYTRUDA® (pembrolizumab, a PD-1 inhibitor) for the treatment of adult patients with locally advanced or metastatic urothelial cancer (la/mUC). This combination is the first approved to offer an alternative to platinum-containing chemotherapy, the current standard of care in first-line la/mUC.
– Trial results to be submitted for presentation at upcoming medical meeting –

Reno, Nevada (UroToday.com) -- Seagen Inc. (Nasdaq: SGEN) and Astellas Pharma Inc. (TSE:4503) announced positive topline results from the Phase 3 EV-302 clinical trial (also known as KEYNOTE-A39) for PADCEV® (enfortumab vedotin-ejfv)