Treating Renal Cell Carcinoma With Tyrosine Kinase Inhibition : Episode 31

Participants Explain Rationale for Different IO/TKI Options for ccRCC

April 15, 2025

Commentary

Article

During a live event, Daniel M. Geynisman, MD, and participants discussed their answers to a poll on which combination to use for a patient with advanced renal cell carcinoma.

Daniel M. Geynisman, MD

Chief, Division of Genitourinary Medical Oncology

Associate Professor, Department of Hematology/Oncology

Fox Chase Medical Center – Temple Health

Philadelphia, PA

CASE SUMMARY

A 65-year-old man presented with back pain for past 6 months and hematuria for 1 week.
Physical examination: palpable mass in epigastric and left hypochondriac region, firm and not tender
No family history of cancer
Laboratory results: hemoglobin, 11.4 g/dL; lactate dehydrogenase, 980 U/L; all others within normal limits
Chest x-ray: widened mediastinum with bilateral hilar enlargement
Ultrasound of abdomen/pelvis showed a left renal mass, 8 cm, with multiple enlarged para-aortic nodes
CT scan of chest, abdomen, and pelvis showed multiple mediastinal and hilar nodes, deposits in left lower lobe of lung, enlarged axillary nodes, and enhancing mass in left renal parenchyma with renal vein infiltration; lytic destruction of L4 and L5 vertebrae, left superior pubic ramus, and right ischium
Fine needle aspiration of renal mass and bone biopsy confirmed metastatic clear cell renal cell carcinoma (ccRCC).

A decision was made to initiate an TKI-ICI regimen. What first-line regimen are you most likely to choose for this patient?

DISCUSSION QUESTION

Please discuss your answer to the poll.

Daniel M. Geynisman, MD: There is not one right answer here, but let's say a decision was made to initiate IO [immunotherapy] plus TKI [tyrosine kinase inhibitor], whether it's for patient preference, your preference, because you were looking for a higher and quicker response rate, whatever that may be. If you chose to do IO/TKI, what first-line regimen are you most likely to choose for this patient? Is that axitinib [Inlyta] plus pembrolizumab [Keytruda], cabozantinib [Cabometyx] plus nivolumab [Opdivo], lenvatinib [Lenvima] plus pembrolizumab, or something else?

Nobody is choosing other, which I think is very appropriate, because there is no other approved IO/TKI regimen. There are others studied, but, but none approved. Since we're divided equally, can somebody tell me why they chose axitinib/pembrolizumab? There are no clearly right answers.

Rana Bilbeisi, MD: I chose the one with axitinib because it's easier to use and discontinue when needed, because it's only a 3-day period in which, if they have to have procedures or [other treatments], you don't have to be off of it for a whole 2 weeks before and after. It makes it easier to utilize. That's the main reason I tend to gravitate to that regimen more than the others.

Wajahat Khan, MD: I chose cabozantinib/nivolumab. In patients who have bone metastases, there are data that support using cabozantinib as opposed to other [TKI].¹ For somebody has sarcomatoid pathology, or papillary renal cell carcinoma, I would choose cabozantinib.

Geynisman: With bony disease, you like cabozantinib. Remember, cabozantinib in a combination, is a dose of 40 mg, not 60 mg, which is the way it's approved for single-agent use.

Christos Kyriakopoulos, MD: I chose lenvatinib primarily because in the CLEAR study [NCT02811861], the overall response rate was higher.² I don't think that there is a right or wrong answer. I have used all 3 combinations. My experience with lenvatinib has been positive. I have seen patients who tolerate lenvatinib pretty well. It's easy to adjust the dose for adverse events. For this particular patient, I would use lenvatinib/pembrolizumab. But for older or frail patients, I usually go with axitinib/pembrolizumab for the reasons that were mentioned earlier.

Geynisman: When you do lenvatinib/pembrolizumab, what dose of lenvatinib do you start with?

Kyriakopoulos: I start with the full dose and then I adjust as needed.

Deepa Jagtap, MD: I chose lenvatinib/pembrolizumab too, but I have not had success having patients stay on the full dose. I pretty much always start at 14 mg [of lenvatinib], and then I try to go down or up based on their tolerance. Most people cannot do 20 mg.

Anand Patel, MD: For this patient, I picked lenvatinib/pembrolizumab because of the clear cell histology, and I think it's pretty well tolerated. Also, when you involve the patient in the decision making, you can offer them the every-6-week infusion [of pembrolizumab], and that gets their attention more than monthly [nivolumab].

Geynisman: That's a good point. Are you using those every-6-weeks [dosing], or are you doing every 3 weeks? Or do you start out with every 3 weeks and then move to every 6 weeks?

Magdalena Flejsierowicz, MD: I start at every 3 weeks, and then maybe for convenience, if things are stable, I do every 6 weeks.

Pallavi Jasti, MD: Typically, with the combinations, you end up assessing them for toxicity pretty frequently. I've stayed at every 3 weeks unless the patient lives very far away and would prefer every 6 weeks schedule.

Patel: We have an oral chemotherapy navigating team, so I sometimes feel pretty comfortable that they're going to call them every week or 2 for the first cycle, so I don't always make them come in. But sometimes if they're going to be needing to come in any way for the first cycle or 2, it might not be a benefit to be [treated] every 6 weeks.

Geynisman: Are [any of you] getting ready to use the subcutaneous versions of nivolumab and pembrolizumab? Is that going to change anything? It's coming—it's here for nivolumab first, and for pembrolizumab as well. It'll be interesting to see how that changes, or doesn't change, what people choose, and how they [can give] a much quicker injection, or potentially even at home.

_{DISCLOSURE: Geynisman previously reported consulting or advisory roles for Pfizer, Exelixis, AstraZeneca, Seattle Genetics/Astellas, Merck, and Bristol Myers Squibb.}