Deciding Factors for Front-Line Therapy in Metastatic RCC


During a Case-Based Roundtable® event, Shilpa Gupta, MD, led a discussion on what factors influence physician decision making for frontline therapy in patients with metastatic renal cell carcinoma in the first article of a 2-part series.


  • Is risk status alone the deciding factor in your first-line treatment decision making?​
    • What about for favorable versus intermediate-risk patients with metastatic renal cell carcinoma (mRCC)?​
  • In the intermediate/high-risk cohort, what factors lead you to think the patient may progress? ​
  • What drives your selection of first-line therapy for favorable-risk clear cell mRCC?

SHILPA GUPTA, MD: I think in the intermediate- to poor-[risk group of patients], nobody's...debating the use of [immunotherapy]-based doublet-therapy, but in the favorable risk [group], that gray zone. The immunotherapy and tyrosine kinase inhibitor [TKI] combination approvals are for patients with favorable-, intermediate-, or poor-risk disease. It's only when you dissect the data that you can make a case for wanting to avoid immunotherapy upfront, but the National Comprehensive Cancer Network guidelines suggest that anyway.1

What drives your selection of first-line therapies? [Is it factors like] better efficacy data, [such as the] response or survival rate? What is the one factor that's most meaningful to you [in making this decision]?

Shilpa Gupta, MD

Shilpa Gupta, MD

Director of Genitourinary Medical Oncology

Taussig Cancer Institute

Co-leader of the Genitourinary Oncology Program

Cleveland Clinic

Cleveland, OH

LISA THOMAS, MD: I also do palliative care for patients, so I'm all about [focusing on their] quality of life and the drug's safety benefit.

GUPTA: So you want to be on the conservative side and maintain people's quality of life, given there's so many regiments to use; understood.

BEI LIU, MD: There's no one standard for all [types of patients] here. [Treatment decisions] depend on the case scenario. For example, in a younger patient with a large disease burden, I'll need to get a quick response, so I usually pick [the treatment] that has a higher response rate. If the patient has mediocre health and isn't high risk, then I'm not in a hurry to need an immediate response [from therapy]. I usually go with something that has the best overall survival data, but adverse events [AEs] are always a consideration for any patient population. For younger people, I rather them live longer if they can tolerate the AEs.

GUPTA: Do you feel comfortable using ipilimumab [Yervoy] and nivolumab [Opdivo] in the frontline setting? A lot of people argue that if you use ipilimumab/nivolumab first, you're giving them a great chance for long-term durability and then you can use a TKI later. But we have seen studies where if you use ipilimumab/nivolumab in the salvage setting, it doesn't produce as good responses. Does that make any difference to you all?

LIU: If someone doesn't need the rapid reduction, I'll go for it. My concern is that for some patients who need the rapid reduction of their disease burden I’ll choose this regimen, but I may not have the chance for them to make it through [and get] long-term benefit.

TAREQ AL BAGHDADI, MD: I only use 2 regimens. Ipilimumab/nivolumab is my go-to regimen for patients with intermediate- or poor-risk disease. But if they have a high burden of disease and I want to choose something that is likely to work...that's [when I use] cabozantinib [Cabometyx] and nivolumab, where the rate of primary progression is about 5%.2

PALLAVI JASTI, MD: Similar to your sentiments, the bulk of the disease...helps me make some decisions. When I need rapid reduction, I go with cabozantinib and nivolumab, but in other intermediate- and high-risk patients where I have the time [to treat them], then I do the doublet immunotherapy regimen.

1. NCCN. Clinical Practice Guidelines in Oncology. Kidney cancer, version 3.2024. Accessed April 17, 2024.
2. Bourlon MT, Escudier B, Burotto M, et al. Nivolumab plus cabozantinib (N+C) vs sunitinib (S) for previously untreated advanced renal cell carcinoma (aRCC): Results from 55-month follow-up of the CheckMate 9ER trial. J Clin Oncol. 2024;4:362. doi:10.1200/JCO.2024.42.4_suppl.362
Related Videos
Video 11 - "Treating Patients With RCC Who Progress Following Adjuvant Therapy"
Related Content