Clinical decision making with immunotherapies in advanced or recurrent endometrial cancer

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    Faculty & Disclosures
    Prof. David Cibula

    General University Hospital, Prague, Czech Republic

    Prof. David Cibula is chair of the Department of Gynaecology, Obstetrics and Neonatology and chair of the Gynaecologic Oncology Centre at the General University Hospital of Charles University in Prague, Czech Republic. read more

    Under the leadership of Prof. Cibula, the Gynaecologic Oncology Centre has grown into one of the largest gynaecological oncology centres in Europe, taking care of over 400 new patients per year.

    Prof. Cibula is a past-president of the European Society of Gynaecological Oncology (ESGO). He is a founder and current chairman of the Central and Eastern European Gynecologic Oncology Group, a collaborative group for clinical trials in gynaecological oncology, which belongs to the European Network of Gynaecological Oncological Trial groups (ENGOT). Prof. Cibula has also founded two charities supporting patients with gynaecological cancers and research in gynaecological oncology, respectively. 

    Prof. Cibula is regularly invited as a speaker at major international meetings and he is the author or co-author of over 250 articles and 31 textbook chapters.

    Prof. David Cibula discloses Advisory Board or Panel fees from AstraZeneca, GSK, Karyopharm Therapeutics, Merck Sharp & Dohme, Novocure and Roche.
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    Clinical decision making with immunotherapies in advanced or recurrent endometrial cancer

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    Prof. David Cibula is chair of the Department of Gynaecology, Obstetrics and Neonatology and chair of the Gynaecologic Oncology Centre at the General University Hospital of Charles University in Prague, Czech Republic. read more

    Under the leadership of Prof. Cibula, the Gynaecologic Oncology Centre has grown into one of the largest gynaecological oncology centres in Europe, taking care of over 400 new patients per year.

    Prof. Cibula is a past-president of the European Society of Gynaecological Oncology (ESGO). He is a founder and current chairman of the Central and Eastern European Gynecologic Oncology Group, a collaborative group for clinical trials in gynaecological oncology, which belongs to the European Network of Gynaecological Oncological Trial groups (ENGOT). Prof. Cibula has also founded two charities supporting patients with gynaecological cancers and research in gynaecological oncology, respectively. 

    Prof. Cibula is regularly invited as a speaker at major international meetings and he is the author or co-author of over 250 articles and 31 textbook chapters.

    Prof. David Cibula discloses Advisory Board or Panel fees from AstraZeneca, GSK, Karyopharm Therapeutics, Merck Sharp & Dohme, Novocure and Roche.

    Take CE/CME Test

    Prof. David Cibula is chair of the Department of Gynaecology, Obstetrics and Neonatology and chair of the Gynaecologic Oncology Centre at the General University Hospital of Charles University in Prague, Czech Republic. read more

    Under the leadership of Prof. Cibula, the Gynaecologic Oncology Centre has grown into one of the largest gynaecological oncology centres in Europe, taking care of over 400 new patients per year.

    Prof. Cibula is a past-president of the European Society of Gynaecological Oncology (ESGO). He is a founder and current chairman of the Central and Eastern European Gynecologic Oncology Group, a collaborative group for clinical trials in gynaecological oncology, which belongs to the European Network of Gynaecological Oncological Trial groups (ENGOT). Prof. Cibula has also founded two charities supporting patients with gynaecological cancers and research in gynaecological oncology, respectively. 

    Prof. Cibula is regularly invited as a speaker at major international meetings and he is the author or co-author of over 250 articles and 31 textbook chapters.

    Prof. David Cibula discloses Advisory Board or Panel fees from AstraZeneca, GSK, Karyopharm Therapeutics, Merck Sharp & Dohme, Novocure and Roche.

    Take CE/CME Test

    Prof. David Cibula is chair of the Department of Gynaecology, Obstetrics and Neonatology and chair of the Gynaecologic Oncology Centre at the General University Hospital of Charles University in Prague, Czech Republic. read more

    Under the leadership of Prof. Cibula, the Gynaecologic Oncology Centre has grown into one of the largest gynaecological oncology centres in Europe, taking care of over 400 new patients per year.

    Prof. Cibula is a past-president of the European Society of Gynaecological Oncology (ESGO). He is a founder and current chairman of the Central and Eastern European Gynecologic Oncology Group, a collaborative group for clinical trials in gynaecological oncology, which belongs to the European Network of Gynaecological Oncological Trial groups (ENGOT). Prof. Cibula has also founded two charities supporting patients with gynaecological cancers and research in gynaecological oncology, respectively. 

    Prof. Cibula is regularly invited as a speaker at major international meetings and he is the author or co-author of over 250 articles and 31 textbook chapters.

    Prof. David Cibula discloses Advisory Board or Panel fees from AstraZeneca, GSK, Karyopharm Therapeutics, Merck Sharp & Dohme, Novocure and Roche.

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    Learning Objectives

    After watching this activity, participants should be better able to:

    • Describe the role of molecular classification in optimal treatment selection for patients with advanced or recurrent endometrial cancer
    • Evaluate the established role of immunotherapies for treating advanced or recurrent endometrial cancer according to guideline recommendations
    • Discuss the impact of utilizing immunotherapy combination strategies for advanced or recurrent endometrial cancer in earlier lines of treatment
    Overview

    In this activity, a gynaecological oncologist considers the expanding role of molecular classification in endometrial cancer and provides an update on the use of immune checkpoint inhibitors to treat patients with advanced or recurrent disease, including key guideline recommendations, supporting data and considerations for clinical practice.

    This activity is jointly provided by USF Health and touchIME. read more

    Target Audience

    This activity has been designed to meet the educational needs of oncologists and pathologists who are involved in the management of patients with endometrial cancer.

    USF Accreditation

    Disclosures

    USF Health adheres to the Standards for Integrity and Independence in Accredited Continuing Education. All individuals in a position to influence content have disclosed to USF Health any financial relationship with an ineligible organization. USF Health has reviewed and mitigated all relevant financial relationships related to the content of the activity. The relevant relationships are listed below. All individuals not listed have no relevant financial relationships.

    Faculty

    Prof. David Cibula discloses Advisory Board or Panel fees from AstraZeneca, GSK, Karyopharm Therapeutics, Merck Sharp & Dohme, Novocure and Roche.

    Content reviewer

    Danielle Walker, DNP, APRN, AGNP-C has no financial interests/relationships or affiliations in relation to this activity.

    Touch Medical Contributors

    Hannah Fisher has no financial interests/relationships or affiliations in relation to this activity.

    USF Health Office of Continuing Professional Development and touchIME staff have no financial interests/relationships or affiliations in relation to this activity.

    Requirements for Successful Completion

    In order to receive credit for this activity, participants must review the content and complete the post-test and evaluation form. Statements of credit are awarded upon successful completion of the post-test and evaluation form.

    If you have questions regarding credit please contact cpdsupport@usf.edu 

    Accreditations

    Physicians

    This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through a joint providership of USF Health and touchIME. USF Health is accredited by the ACCME to provide continuing medical education for physicians.

    USF Health designates this enduring material for a maximum of 1.0 AMA PRA Category 1 CreditsTM.  Physicians should claim only the credit commensurate with the extent of their participation in the activity.

    Advanced Practice Providers

    Physician Assistants may claim a maximum of 1.0 Category 1 credits for completing this activity. NCCPA accepts AMA PRA Category 1 CreditTM from organizations accredited by ACCME or a recognized state medical society.

    The AANPCP accepts certificates of participation for educational activities approved for AMA PRA Category 1 CreditTM by ACCME-accredited providers. APRNs who participate will receive a certificate of completion commensurate with the extent of their participation.

    Date of original release: 6 June 2024. Date credits expire: 6 June 2025.

    If you have any questions regarding credit, please contact cpdsupport@usf.edu

    This activity is CE/CME accredited

    To obtain the CE/CME credit(s) from this activity, please complete this post-activity test.

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    Topics covered in this activity

    Gynaecological Cancers / Immunotherapy
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    This activity is funded by:

    An independent medical education grant from Merck & Co, Inc.
    This activity is jointly provided by USF Health and touchIME.

    The information provided by this CME activity is for continuing education purposes only and is not meant to substitute for the independent medical/clinical judgement of a healthcare provider relative to diagnostic and treatment options of a specific patient’s medical condition.

    USF is an Equal Opportunity / Affirmative Action / Equal Access Institution.

    USF Health is accredited by the Accreditation Council for Continuing Medical Education, the American Nurses Credentialing Center and the Accreditation Council for Pharmacy Education to provide continuing education to healthcare professionals. As an accredited provider, USF Health is required to disclose personal information to relevant accredited bodies that certify CME to process credits/contact hours, comply with reporting requirements, and for internal recordkeeping and regulatory purposes. USF Health does not share or sell any individual’s contact information or unique identifiers to any commercial supporter, advertiser, or third party without the specific permission of the individual.

    Unapproved products or unapproved uses of approved products may be discussed by the faculty; these situations may reflect the approval status in one or more jurisdictions. The presenting faculty have been advised by touchIME and USF Health to ensure that they disclose any such references made to unlabelled or unapproved use. No endorsement by touchIME or USF Health of any unapproved products or unapproved uses is either made or implied by mention of these products or uses in touchIME or USF Health activities. touchIME and USF Health accept no responsibility for errors or omissions.

    This content is intended for healthcare professionals outside of the UK only.

    Date of original release: 6 June 2024.
    Date credits expire: 6 June 2025.

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    touchEXPERT OPINIONS
    Clinical decision making with immunotherapies in advanced or recurrent endometrial cancer
    1 CE/CME credit
    Question 1/5
    Which of the following would you assess to establish an integrated molecular classification for your patient with endometrial cancer?

    HER2, human epidermal growth factor receptor 2; MMR, mismatch repair; NTRK, neurotrophic tyrosine receptor kinase; POLE, polymerase epsilon.

    The 2022 ESMO clinical practice guideline for endometrial cancer states that molecular classification is established by assessing POLE, p53 and MMR status. 

    Abbreviations

    ESMO, European Society for Medical Oncology; MMR, mismatch repair; POLE, polymerase epsilon. 

    Reference

    Oaknin A, et al. Ann Oncol. 2022;33:860–77.

    Question 2/5
    In the 2022 ESMO clinical practice guideline for endometrial cancer, which molecular characteristic is used to help select the most appropriate second-line treatment for patients with advanced/recurrent endometrial cancer?

    ESMO, European Society for Medical Oncology; MMR, mismatch repair; PD-L1, programmed death-ligand 1; POLEmut, polymerase epsilon ultramutated.

    The 2022 ESMO clinical practice guideline for endometrial cancer differentiates second-line treatment by the tumour MMR status.1 Approvals of second-line ICI therapies since the ESMO clinical practice guideline was published are also based on MMR status.2,3

    Abbreviations

    ESMO, European Society for Medical Oncology; ICI, immune checkpoint inhibitor; MMR, mismatch repair. 

    References

    1. Oaknin A, et al. Ann Oncol. 2022;33:860–77.
    2. EMA. Dostarlimab SmPC. Available at: https://bit.ly/3vnfGpR (accessed 10 May 2024).
    3. EMA. Pembrolizumab SmPC. Available at: https://bit.ly/3PvRLeN (accessed 10 May 2024)
    Question 3/5
    You have a patient with MSS/pMMR advanced endometrial cancer that has recurred after first-line treatment with platinum-based chemotherapy. Based on current approvals and guidelines, what immunotherapy-based treatment would you consider for this patient’s next line of therapy?

    MSS, microsatellite stable; pMMR, mismatch repair proficient.

    Pembrolizumab plus lenvatinib is currently the only ICI-based treatment approved by the EMA and FDA for use in the second-line setting for patients with MSS/pMMR endometrial cancer,1–4 and is recommended in the ESMO guidelines.5 According to the 2022 ESMO clinical practice guideline for endometrial cancer, second-line ICI treatment options for patients with MSI-H/dMMR tumours are dostarlimab or pembrolizumab monotherapy, as well as pembrolizumab plus lenvatinib.5

    Abbreviations

    dMMR, MMR deficient; EMA, European Medical Association; ESMO, European Society for Medical Oncology; FDA, US Food and Drug Administration; ICI, immune checkpoint inhibitor; MMR, mismatch repair; MSI-H microsatellite instability-high; MSS, microsatellite stable; pMMR, MMR proficient.

    References

    1. EMA. Dostarlimab SmPC. Available at: https://bit.ly/3vnfGpR (accessed 10 May 2024).
    2. EMA. Pembrolizumab SmPC. Available at: https://bit.ly/3PvRLeN (accessed 10 May 2024).
    3. FDA. Dostarlimab PI. Available at: www.accessdata.fda.gov/drugsatfda_docs/label/2024/761174s010lbl.pdf (accessed 10 May 2024).
    4. FDA. Pembrolizumab PI. Available at: www.accessdata.fda.gov/drugsatfda_docs/label/2024/125514s160lbl.pdf (accessed 10 May 2024).
    5. Oaknin A, et al. Ann Oncol. 2022;33:860–77.
    Question 4/5
    You have a patient with MSI-H/dMMR advanced endometrial cancer and you are discussing the possibility of starting treatment with dostarlimab plus carboplatin/paclitaxel. They ask you for more information about the side effects of this combination. What do you tell them?

    dMMR, mismatch repair deficient; MSI-H, microsatellite instability-high.

    ICIs have a different side effect profile compared with chemotherapy and irAEs can affect any organ system.1 irAEs can occur at any point during treatment with ICIs, including up to 12 months after cessation of treatment.1,2 Guidelines have been developed to support the management of irAEs according to grade: patients experiencing grade 1 irAEs can usually continue ICI therapy; therapy should be temporarily withheld in patients experiencing a grade ≥2 irAE; rechallenge of ICI therapy in patients who have experienced a grade 3 or 4 irAE should be risk-adjusted based on anticipated benefit with therapy vs the potential for toxicity.2,3

    Abbreviations

    ICI, immune checkpoint inhibitor; irAE, immune-related adverse event. 

    References

    1. Medina P, et al. J Pharm Pract. 2020;33:338–49.
    2. Brahmer JR, et al. J Immunother Cancer. 2021;9:e002435.
    3. Haanen J, et al. Ann Oncol. 2022;33:1217–38.
    Question 5/5
    Your patient has just been diagnosed with advanced endometrial cancer. Immunohistochemistry shows the tumour is dMMR. Based on the latest data, which of the following first-line treatment approaches would you consider for this patient, assuming all are approved and available in your region?

    dMMR, mismatch repair deficient; ICI, immune checkpoint inhibitor; TKI, tyrosine kinase inhibitor.

    First-line treatment options available for dMMR endometrial cancer include platinum-based chemotherapy and ICI plus CP.1,2 Data from the RUBY/ENGOT-en6, NRG-GY018/KEYNOTE-868 and AtTEnd/ENGOT-en7 clinical trials show that patients with dMMR advanced or recurrent endometrial cancer receiving an ICI plus CP had a significantly longer PFS vs patients receiving placebo plus CP (p<0.0001; p<0.001 and p=0.0005, respectively).3–5 

    Abbreviations

    CP, carboplatin and paclitaxel; dMMR, mismatch repair deficient; ICI, immune checkpoint inhibitor; PFS, progression-free survival. 

    References

    1. EMA. Dostarlimab SmPC. Available at: https://bit.ly/3vnfGpR (accessed 10 May 2024).
    2. NCCN Guidelines. Uterine Neoplasms Version 2.2024. Available at: www.nccn.org/professionals/physician_gls/pdf/uterine.pdf (accessed 10 May 2024).
    3. Mirza MR, et al. Presented at: SGO 2023, Tampa, FL, USA. 25–28 March 2023. Abstr LBA11.
    4. Eskander RN, et al. N Engl J Med. 2023;388:2159–70.
    5. Colombo N, at al. Presented at: ESMO Congress 2023, Madrid, Spain. 20–24 October 2023. Abstr LBA40.
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    This activity is funded by:

    An independent medical education grant from Merck & Co, Inc.
    This activity is jointly provided by USF Health and touchIME.

    The information provided by this CME activity is for continuing education purposes only and is not meant to substitute for the independent medical/clinical judgement of a healthcare provider relative to diagnostic and treatment options of a specific patient’s medical condition.

    USF is an Equal Opportunity / Affirmative Action / Equal Access Institution.

    USF Health is accredited by the Accreditation Council for Continuing Medical Education, the American Nurses Credentialing Center and the Accreditation Council for Pharmacy Education to provide continuing education to healthcare professionals. As an accredited provider, USF Health is required to disclose personal information to relevant accredited bodies that certify CME to process credits/contact hours, comply with reporting requirements, and for internal recordkeeping and regulatory purposes. USF Health does not share or sell any individual’s contact information or unique identifiers to any commercial supporter, advertiser, or third party without the specific permission of the individual.

    Unapproved products or unapproved uses of approved products may be discussed by the faculty; these situations may reflect the approval status in one or more jurisdictions. The presenting faculty have been advised by touchIME and USF Health to ensure that they disclose any such references made to unlabelled or unapproved use. No endorsement by touchIME or USF Health of any unapproved products or unapproved uses is either made or implied by mention of these products or uses in touchIME or USF Health activities. touchIME and USF Health accept no responsibility for errors or omissions.

    This content is intended for healthcare professionals outside of the UK only.

    Date of original release: 6 June 2024.
    Date credits expire: 6 June 2025.

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