Unique Challenges of Using IO/TKI Combinations in Metastatic RCC

Robert J. Motzer, MD

Section Head, Kidney Cancer, Genitourinary Oncology Service

Jack and Dorothy Byrne Chair in Clinical Oncology

Memorial Sloan Kettering Cancer Center

New York, NY

[Read Part 1 here]

DISCUSSION QUESTIONS:

• What are your reactions to the CheckMate 9ER (NCT03141177) data? ​
• Do you have experience with cabozantinib (Cabometyx) plus nivolumab (Opdivo) in patients with renal cell carcinoma (RCC)?

ROBERT J. MOTZER, MD: Have you used this program for your patients with clear cell RCC? What’s been your experience? What are the main adverse events [AEs] you see? Are there certain subsets that you feel might benefit from this more than others? The cabozantinib has always been presented as being better in bone metastasis, is that something you’ve seen in your clinic?

DAYA SHARMA, MD: I currently have 2 patients on cabozantinib/nivolumab, but incidentally, both are on dialysis. Initially, I was not sure how to start cabozantinib for those patients. I talked to a couple of [experts], then I made my own judgment. I started with 20 mg, and within a few weeks, I raised the dose to 40 mg. These patients are doing very well for the last 8 or 9 months and they have not dealt with any toxicity in the skin or diarrhea, so I’m surprised. They tell me that they take their pill every day. I believe that 40 mg is a very well tolerated pill as compared with 60 mg even as a monotherapy. My experience has been very positive with cabozantinib/nivolumab especially in our patients on dialysis. I was scared how they would react, but they did very well.

MOTZER: That’s very good feedback. Have others used cabozantinib/nivolumab?

ARUN BHANDARI, MD: I have used in a patient with high-risk disease. It was very interesting; this patient had a brain bleed. I was a little reluctant to use with the brain bleed, whether it would get worse or not. I think it was a bleed in the metastatic disease in the brain. He was seen at Johns Hopkins Medicine, they said to continue, and he did well for probably about 9 months and then he passed away from a cardiac event.

MOTZER: Did you think the brain bleed was related to the combination…like hypertension? Or was that related to the brain metastasis?

BHANDARI: I think the brain metastasis had a bleed. The concern was, should I use it to start with, is it going to get worse, and fortunately it didn’t get worse. He responded for about 6 to 9 months, and he was doing well, and other cardiac issues caused his passing.

JOSE SILVA, MD: I tend to save cabozantinib for a second-line option, because it has multiple mechanisms that the other drugs don’t. I try to maximize the drug dose and I don’t want the AEs of fatigue and some gastrointestinal AE to be overlapping between the immune checkpoint inhibitor and cabozantinib. So I try to save it for a second line.

MOTZER: I hear that quite often, and I think that cabozantinib is our go-to drug in second-line therapy. I like to use it in the second line. It hits a lot of different kinases, [and maybe is effective] for more resistant tumors. I go with the other options in first line and save the cabozantinib for the second line. It sounds like that’s been your practice also. I think that’s very reasonable. That’s the same [as] what I generally do. There are some patients for whom I use cabozantinib/nivolumab up front and those are patients where I’m very concerned about the blood pressure issues, or if it’s predominantly bone metastasis. If patients have bone metastasis only, then based on this idea that perhaps cabozantinib is better in bone [disease], I’ve treated some of those patients with cabozantinib/nivolumab.