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    Faculty & Disclosures
    Dr Toni Choueiri

    Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

    Dr Toni Choueiri is the director of the Lank Center for Genitourinary (GU) Oncology at Dana-Farber Cancer Institute (DFCI), co-leader of the Kidney Cancer Program at Dana-Farber/Harvard Cancer Center, and the Jerome and Nancy Professor of Medicine at Harvard Medical School. He is the medical director of International Strategic Initiatives at DFCI and past president of the Medical Staff at DFCI (2016–2018). read more

    Dr Choueiri is interested in developing novel experimental therapies and biomarkers in GU malignancies, including renal cell carcinoma (RCC). In a series of New England Journal of Medicine articles, Dr Choueiri and colleagues have made seminal observations that have defined and evolved the treatment of metastatic RCC and led to the approval of several therapies such as cabozantinib, pazopanib, avelumab + axitinib, cabozantinib + nivolumab, pembrolizumab + lenvatinib, and adjuvant pembrolizumab. His research also focuses on the epidemiology, diagnosis and treatment outcomes of GU cancers, especially through having co-established the International Metastatic RCC Database Consortium criteria for RCC risk stratification. His biomarker work has shed light on complex immunogenomics mechanisms contributing to response and resistance to targeted therapy and immunotherapy. 

    He received the George Canellos Award for Excellence in Clinical Investigation and Patient Care from DFCI in 2013, the Eugene Schonfeld Award from the Kidney Cancer Association in 2016, and is a 2021 Giants of Cancer Care inductee. He serves on the National Comprehensive Cancer Network Kidney Cancer Panel, KidneyCan Board and the National Cancer Institute GU steering committee. 

    Dr Choueiri’s work has been published in journals such as the New England Journal of Medicine, Journal of American Medical Association (JAMA), JAMA Oncology, The Lancet, Lancet Oncology and Journal of Clinical Oncology. 

    He lectures frequently around the world and has over 675 PubMed-indexed publications on GU cancers.

    Dr Toni Choueiri discloses: Advisory board/Panel and Consultancy fees and Grants/Research support from Aravive, AstraZeneca, Aveo, Bayer, Bristol Myers Squibb, Calithera, Circle Pharma, Eisai, EMD Serono, Exelixis, GlaxoSmithKline, Infinity, Ipsen, Janssen, Kanaph, Lilly, Merck, Nikang, Novartis, Pfizer, Roche, Sanofi-Aventis, Surface Oncology, Takeda and Tempest Therapeutics. Stock/Shareholder (self-managed) Osel, Pionyr and Tempest Therapeutics.
    Dr Cristina Suárez

    Vall d´Hebron University Hospital, Barcelona, Spain

    Dr Cristina Suárez is a medical oncologist at the Vall d´Hebron University Hospital in Barcelona, Spain. read more

    Dr Suárez received her MD in Medicine and Surgery at the Autonomous University of Barcelona. She received specialist training in medical oncology at the Faculty of Medicine, Autonomous University of Barcelona and Hospital del Mar – Parc de Salut, Barcelona. In 2008, she joined the Oncology Department at Vall d’Hebron University Hospital as a physician (attending staff) in the Genitourinary, Central Nervous System, Sarcoma and Tumours of Unknown Origin Program.

    In 2018, Dr Suárez obtained her cum laude qualification when she completed her doctorate studies with the doctoral thesis: ‘Prognostic value of genetic alterations in the mTOR pathway of patients with metastatic renal cell carcinoma treated with mTOR inhibitors’.

    She has been co-investigator and principal investigator in several clinical trials related to genitourinary malignancies, and is the author or co-author of more than 100 scientific papers, posters and book chapters focused on the area of genitourinary tumours.

    She is vice president of SOGUG (Spanish Oncology Genitourinary Group), an active member of several oncology societies such as ASCO, ESMO, SEOM and SOGUG, and a scientific committee member of ASCO and ESMO.

    Dr Cristina Suárez discloses: Advisory board/Panel and Consultancy fees from Astellas, Bayer, Bristol Myers Squibb, Ipsen, Merck & Co, Inc. (MSD), Pfizer, Roche and Sanofi. Grants/Research support from Ipsen. Speaker’s Bureau fees from Astellas, Bristol Myers Squibb, Ipsen, Pfizer and Roche.
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    What is the rationale for use of combination therapies in advanced RCC?
    First-line combination therapies in advanced RCC: What do the latest clinical data tell us?
    Side effects of combination therapies for advanced RCC: What is best practice for management?
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    touchIN CONVERSATION
    A relaxed discussion between two faculty focussed on real world clinical issues. Useful tips below will show how to navigate the activity. Join the conversation. Close

    Improving outcomes for patients with advanced RCC: What is the role of emerging combination therapies in the first-line setting?

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    Learning Objectives

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

    • Evaluate the rationale for the use of combination therapy in patients with advanced RCC
    • Discuss the latest efficacy and safety data for established and emerging combination therapies in first-line advanced RCC
    • Apply best practice in the management of adverse events associated with combination therapies for first-line advanced RCC
    Overview

    In this activity, experts in the management of renal cell carcinoma (RCC) respond to questions from the renal oncology community on the rationale for use of combination therapies in advanced RCC, the latest clinical evidence for their use in the first-line setting, and best practice for managing side effects associated with combination therapies for advanced RCC.

    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 validated oncology specialists, oncology surgeons and radiologists involved in the management of advanced renal cell carcinoma.

    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 financial relationships are listed below. All individuals not listed have no relevant financial relationships.

    Faculty 

    Dr Toni Choueiri discloses: Advisory board/Panel and Consultancy fees and Grants/Research support from Aravive, AstraZeneca, Aveo, Bayer, Bristol Myers Squibb, Calithera, Circle Pharma, Eisai, EMD Serono, Exelixis, GlaxoSmithKline, Infinity, Ipsen, Janssen, Kanaph, Lilly, Merck, Nikang, Novartis, Pfizer, Roche, Sanofi-Aventis, Surface Oncology, Takeda and Tempest Therapeutics. Stock/Shareholder (self-managed) Osel, Pionyr and Tempest Therapeutics.

    Dr Cristina Suárez discloses: Advisory board/Panel and Consultancy fees from Astellas, Bayer, Bristol Myers Squibb, Ipsen, Merck & Co, Inc. (MSD), Pfizer, Roche and Sanofi. Grants/Research support from Ipsen. Speaker’s Bureau fees from Astellas, Bristol Myers Squibb, Ipsen, Pfizer and Roche.

    Content reviewer

    Brandon Manley, MD has no financial interests/relationships or affiliations in relation to this activity.

    Touch Medical Director

    Adriano Boasso and Sola Neunie have 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 0.75 AMA PRA Category 1 CreditTM.  Physicians should claim only the credit commensurate with the extent of their participation in the activity.

    The European Union of Medical Specialists (UEMS) – European Accreditation Council for Continuing Medical Education (EACCME) has an agreement of mutual recognition of continuing medical education (CME) credit with the American Medical Association (AMA). European physicians interested in converting AMA PRA Category 1 CreditTM into European CME credit (ECMEC) should contact the UEMS (www.uems.eu).

    Advanced Practice Providers

    Physician Assistants may claim a maximum of 0.75 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: 04 August 2022. Date credits expire: 04 August 2023.

    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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    Paradigm towards Tailored Therapies and Complete Responses in the Treatment of Metastatic Renal Cell Carcinoma

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    Topics covered in this activity

    Renal Cancer / Genitourinary Cancer / Immunotherapy
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    This Activity Is Funded By:

    An independent medical education grant from Exelixis, Inc., and Merck and 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 judgment 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.

    Date of original release: 04 August 2022. Date credits expire: 04 August 2023.

    Claim Credit
    touchIN CONVERSATION
    Improving outcomes for patients with advanced RCC: What is the role of emerging combination therapies in the first-line setting?
    0.75 CE/CME credit
    Question 1/5
    Your patient is a 55-year-old man who has recently been diagnosed with non-resectable sRCC and an intermediate IMDC risk. Based on clinical trial evidence, which of the following therapeutic options would you prescribe in the first line?

    IMDC, International Metastatic RCC Database Consortium; sRCC, sarcomatoid renal cell carcinoma.

    Ipilimumab + nivolumab in combination have been established as a feasible first-line therapeutic option for patients with sRCC. In a post hoc analysis of the CheckMate 214 trial of patients with sRCC (n=139 intermediate/poor risk), ORR was 61% with ipilimumab + nivolumab versus 23% with sunitinib, and the mPFS was 26.5 months versus 5.1 months, respectively. mOS also favoured ipilimumab + nivolumab versus sunitinib; after a minimum of 42 months’ follow-up, mPFS was not reached versus 14.4 months, respectively. 

    Abbreviations

    mOS, median overall survival; mPFS, median progression-free survival; ORR, objective response rate; sRCC, sarcomatoid renal cell carcinoma.

    Reference

    Tannir NM, et al. Clin Cancer Res. 2021;27:78–86.

    Question 2/5
    You have decided to initiate cabozantinib + nivolumab in your patient, and they ask you what kind of treatment response they might expect. What should you tell them, based on the clinical trial data for first-line treatment of patients with advanced RCC?

    mOS, median overall survival; RCC, renal cell carcinoma.

    In the CheckMate 9ER trial (N=651), an ORR of 56% was observed in treatment-naive patients with advanced RCC receiving cabozantinib + nivolumab versus 27% in patients receiving sunitinib.1 After a median follow-up of 32.9 months, the mOS was 37.7 months versus 34.3 months for sunitinib.2  

    Abbreviations

    ORR, objective response rate; OS, overall survival; RCC, renal cell carcinoma.

    References

    1. Choueiri TK, et al. N Engl J Med. 2021;384:829–41.
    2. Powles T, et al. J Clin Oncol. 2022;40(Suppl. 6):350.
    Question 3/5
    You are considering treatment options for your 69-year-old female patient who has recently been diagnosed with favourable-risk, non-resectable advanced RCC. Which of the following combination therapies would be your preferred option?

    RCC, renal cell carcinoma.

    Lenvatinib + pembrolizumab is approved for patients with favourable-risk, advanced RCC.1,2 Data from the CLEAR trial showed that treatment with lenvatinib + pembrolizumab or lenvatinib + everolimus resulted in ORRs of 71% and 54%, respectively, compared with 36% with sunitinib.3 Lenvatinib + pembrolizumab, but not lenvatinib + everolimus, was associated with a significantly longer OS compared with sunitinib.3 The phase III, IMmotion151 trial of atezolizumab + bevacizumab versus sunitinib showed no OS benefit;4 the regimen is not recommended for first-line treatment of advanced RCC.1,2 Ipilimumab + nivolumab is only approved for patients with intermediate-/poor-risk advanced RCC.1,2 

    Abbreviations

    ORR, objective response rate; OS, overall survival; RCC, renal cell carcinoma.

    References

    1. Motzer RJ, et al. J Natl Compr Canc Netw. 2022;20:71–90. 
    2. Powles T, et al. Ann Oncol. 2021;32:1511–9.
    3. Motzer RJ, et al. N Engl J Med. 2021;384:1289–300.
    4. Rini BI, et al. Lancet. 2019;393:2404–15.
    Question 4/5
    Which commonly occurring side effect of VEGFR-TKI treatment in patients with RCC is associated with treatment efficacy and reflects the mechanism of action of the agent?

    RCC, renal cell carcinoma; TKI, tyrosine kinase inhibitor; VEGFR, vascular endothelial growth factor receptor.

    Hypertension is a common side effect observed in patients treated with TKIs. TKI-induced hypertension is an early phenomenon and normally develops within the first few weeks of commencement of VEGFR-TKI treatment. VEGFR-TKI-induced hypertension is considered to be caused by inhibition of VEGF signalling, which results in decreased nitric oxide and increased endothelin production, thus leading to vasoconstriction. A retrospective study of 52 patients with metastatic RCC suggested that TKI-induced hypertension is indicative of a positive treatment response in metastatic RCC.

    Abbreviations

    RCC, renal cell carcinoma; TKI, tyrosine kinase inhibitor; VEGF, vascular endothelial growth factor; VEGFR, VEGF receptor. 

    Reference

    Gadd M, et al. Cancer Rep. 2020;3:e1275.

    Question 5/5
    You have a patient with a history of psoriasis. She has poor-risk RCC and, following resection, you are treating her with nivolumab + cabozantinib. At her last review, she described some joint pain, and psoriatic lesions have appeared on her elbows. What do you do?

    RCC, renal cell carcinoma.

    Dose reductions are not recommended with nivolumab; grade 3 irAEs (and some grade 2 irAEs) are generally managed by withholding dosing and/or treating with immunosuppressive therapy.1 There are various types of immunosuppressive therapies to manage irAEs. Depending on the severity of the irAE, low doses of corticosteroids, such as prednisone or methylprednisolone, are typically used, with a taper of at least 4 weeks.2 Nivolumab discontinuation should be considered only for recurrent severe or life-threatening irAEs, or for patients who still require corticosteroids within 12 weeks of initiating them.1

    Abbreviation

    irAE, immune-related adverse event.

    References

    1. FDA. Nivolumab PI. Available at: www.accessdata.fda.gov/drugsatfda_docs/label/2021/125554s090lbl.pdf (accessed 15 July 2022).
    2. McGregor B, et al. Cancer Treat Rev. 2022;103:102333.
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    This Activity Is Funded By:

    An independent medical education grant from Exelixis, Inc., and Merck and 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 judgment 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.

    Date of original release: 04 August 2022. Date credits expire: 04 August 2023.

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