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

  • Downloads including slides are available for this activity in the Toolkit
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

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.


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.


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



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 (

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

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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  • Downloads including slides are available for this activity in the Toolkit

Topics covered in this activity

Renal Cancer / Genitourinary Cancer / Immunotherapy
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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. 


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


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  


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


  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 


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


  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.


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


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


irAE, immune-related adverse event.


  1. FDA. Nivolumab PI. Available at: (accessed 15 July 2022).
  2. McGregor B, et al. Cancer Treat Rev. 2022;103:102333.
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