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Homepage – Forum Forums Research, Clinical Trials, and New Treatments PADCEV and Immunotherapy combo is a game changer for advanced bladder cancer

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    This is the statement posted at FDA site with the heading FDA approves enfortumab vedotin-ejfv with pembrolizumab for locally advanced or metastatic urothelial cancer

    On December 15, 2023, the Food and Drug Administration (FDA) approved enfortumab vedotin-ejfv (Padcev, Astellas Pharma) in combination with pembrolizumab (Keytruda, Merck) for patients with locally advanced or metastatic urothelial cancer (la/mUC). FDA previously granted accelerated approval to this combination for patients with la/mUC who are ineligible for cisplatin-containing chemotherapy.   The excellent result of the clinical trial EV-302 which compared the combo treatment with cisplatin based chemotherapy as the first line treatment for la/mUC.  In the EV-302 phase 3 study of 886 untreated patients, the combo produced a median overall survival (OS) rate of 31.5 months compared to 16.1 months for chemo. The combo produced similar success in progression-free survival (PFS), reducing the risk of disease progression or death by 55%. Patients on the combo regimen lived a median of 12.5 months without progression, versus 6.3 months for the chemo arm. *1

    In the BCC Webinar on clinical trials, Dr. Peter Black mentioned that the presentation of the result of Phase 3 clinical trial of the combination PADCEV (enfortuymab vedotin-ejfv) and Keytruda (Pembrolizumab  had received a standing ovation from participants during the European Society for Medical Oncology (ESMO) in October, 2023.

    It has been known cisplatin works well for bladder cancers, so up to now, cisplatin based chemotherapy such as the combination two different chemotherapy drugs, i.e. Gemcitabine and Cisplatin has been the first line treatment for la/mUC.   However it is known that cancers tend to develop resistance to chemotherapy over time.  But, after platinum-based chemotherapy, there is no internationally accepted standard of care. Single-agent paclitaxel and docetaxel are commonly used worldwide.  *2

    In 2017,  two immunotherapy drugs, Pembrolizumab (Keytruda) by Merck and  Atezolizumab (Tecentriq) by Roche were approved as the 2nd line treatment for la/mUC when the first line chemotherapy failed.   Keytruda is PD-1 immune checkpoint inhibitor and Tecentriq is PD-L1 in immune check point inhibitor.  Both drugs had shown similar efficacies and side effects.   The clinical trial which led to the approval of Keytruda showed the median overall survival was 10.3 months in the Keytruda group as compared with 7.4 moths in the chemotherapy group.  The estimated progression-free survival rate at 12 months was 16.8%  in the pembrolizumab group and 6.2% in the chemotherapy group.  Though Keytruda resulted in modest improvement over chemotherapy, Keytruda improved significant durability once the treatment worked.

    PADCEV belongs to a group of drugs called Antibody-Drug Conjugate (ADC).  ADC uses synthesized human antibody as drug delivery vehicle which carries a load of cytotoxin, which has anti-tumor activities.  PADCEV targets NECTIN-4 protein which are often highly expressed on cell membrane of bladder cancers.  Once PADCEV binds to NECTIN-4 of cancer cell, it releases Monomethyl auristatin E (MMAE) is a very potent antimitotic agent that inhibits cell division by blocking the formation of microtubules which is almost the final step of the cell division cycle, leading to the death of the cell.   In December, 2019 FDA approved PADCEV as the third line treatment for la/mUC when the 2nd line treatment immunotherapy failed.  I believe PADCEV became available for patients in Canada in 2022. *3

    Then it has become a bit complicated.    After, PADCEV was approved by FDA in December, 2019.  In June 2020,  FDA approved another immunotherapy Drug (PD-L1 inhibitor)  Avelumab (Bavencio) as maintenance treatment for la/mUC immediately after the first line cisplatin based chemotherapy for those patient which did not progress during the chemotherapy treatment.   The clinical trial of Avelumab (Bavencio) improved over all survival at 1 year to 71.3% compared to 58.4% in the group who just received best supportive care alone.  Health Canada approved Avelumab (Bavencio) in January 2021 for bladder cancer.   I think Avelumab (Bavencio) became available for patients in Canada after March, 2021. *4

    Because the PADCEV and Keytruda combo treatment as the first line treatment for la/mUC doubled over all survival and progression free survival with durability over traditional cisplatin based chemotherapy, the combo is expected to be the standard 1st line treatment for la/mUC.   The combo treatment  may make the role of Avelumab irrelevant.    Both PADCEV and Keytruda are already approved drug in Canada.   So, the approval process for the combo treatment may take less time.  Lets hope so.  A challenge is the price of the combo treatment.  A US industry paper is saying that PADCEV + Keytruda combo treatment can initially cost Medicare per patient $435K annually, compared to platinum based chemotherapy only $3.5K , and chemotherapy with Avelumab maintenance $96K.    *5

    Zitter Insights polled 35 commercial payers covering 116.7 million lives, 26 Medicare payers covering 42.3 million lives, 50 oncologists and 52 practice managers about their management of and prescribing for bladder cancer. Payers said that an annualized net price for Padcev + Keytruda between $189,000 and $204,000 would be appropriately priced, while a price more than $281,000 would be too expensive, leading to their not covering or highly restricting the regimen. *6

    A 2020 study shows that the cost of the same cancer drug costs about 2.31 times in the US compared European countries.  For example, Keytruda costs $14,167 monthly in the US whereas it costs $9,150 in UK, $7600 in Germany and $8,300 in France.  I expect it is costing Canada similar to European countries.    I hope Padcev + Keytruda combo treatment will become accessible to Canadian patients soon.

    I will list the links to related studies and documents  in the following post.


    The links to relevant information.   I tried to use the link but the the whole text disappeared.  The link must be copied and pasted in any search engine.  Sorry for inconvenience.   Maybe the keymaster can edit and see the link function works.

    FDA announcement


    New England Journal of Medicine (NEJM)  2024  2 mins video


    Dr, Peter Black explains significance of the combo treatment .  BCC Webinar December, 2023   Clinical Trials Demystified  

    “”      Start at 15:00

    Urotoday journal –  Detail results from EV-302 clinical trial


    Immune checkpoint inhibitor 5 mint video – Harvard Medical School


    The efficacy and side effects of Keytruda – PD-1 inhibitor   May 2017 NEJM


    1 min video on Mechanism of Action of PADCEV 


    The result of the clinical trial of PADCEV alone as 3rd line treatment  Feb, 2021 NEJM


    Definition of Locally advanced bladder cancers Translational Andrology and Urology –  2016  Read the first section in Abstract


    Pricing of the combo treatment – American Society of Clinical Oncology Journal  Oct, 2023


    Pricing of the combo treatment – Prime Therapeutics   



    It seems that PADCEV and Keytruda combination treatment for locally advanced and metastatic urothelial carcinoma is already in the hand of CADTH for Reimbursement Review.  CADTH is asking patient/clinician input from April 9, 2024 till June 3, 2024.   CADTH is limiting input from patients group rather than individual.  So, if any patient or caregiver is interested giving input, I think technically you should be able to give your input through BCC.     Note that CADTH is now called  Canada’s Drug Agency.    CADTH stands for Canadian Agency for Drugs and Technology in Health. “”.


    Below is the steps for CADTH Reimbursement application process, which is taken from CADTH site.

    1. Pre-submission Phase
    2. Application Phase
    3. Stakeholder Input
      1. Patient Group Input
      2. Clinician Group Input
      3. Drug program Input
    4. Review Phase
      1. Initiation of the Review
      2. CADTH Review Reports
    5. Recommendation Phase
      1. Expert Committees
        1. The pan-Canadian Oncology Drug Review (pCODR) Expert Review committee (pERC) is used for drugs that are reviewed though CADTH’s  pCODR process.   The expert committees may recommend that a drug be reimbursed; that a drug be reimbursed with conditions; or that a drug not be reimbursed. The expert committee meeting schedule is available on the CADTH website.
      2. Draft Recommendation
      3. Final Recommendation
    6. Implementation Phase






    Joe, thank you for this information. For your point ” So, if any patient or caregiver is interested giving input, I think technically you should be able to give your input through BCC” how can we give our input to BCC? Please advise. Thank you and to all the BCC volunteers for this great forum

    • This reply was modified 2 weeks, 5 days ago by LP. Reason: missing word

    Hi LP,
    You can sign up to provide your input here:

    We currently are in need of patients to provide input if they have received PADCEV in the past.


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