Martin H. Voss, MD: Once you’ve decided on whether to pursue I/O [immunotherapy]-I/O vs an I/O-TKI [tyrosine kinase inhibitor], we have several I/O and VEGF combination regimens to consider. Sandy, I’ll turn to you again for this question. Bob has shown us some data that were presented at the 2021 ASCO [American Society of Clinical Oncology annual meeting] to speak to the differences for cabozantinib-nivolumab across various subgroups, liver metastases and bone metastases, and the IMDC [International Metastatic Renal Cell Carcinoma Database Consortium] risk data breaking down into intermediate and poor. I’m curious to hear your thoughts regarding the different I/O-TKI regimens, their mechanism of action, the data we’ve seen so far, and how patient features can help you decide between these regimens. Is it the patient who drives the decision, or is it the comfort of the investigator with the data and their experience with the drugs?

Sandy Srinivas, MBBS: Before I go to that, I would like to add one thing about the ipilimumab-nivolumab data. Not to harp on CRs [complete responses], but the biggest asset is that all of us have a handful of patients who are now off all therapy. That’s the most gratifying thing. I know it feels like the high-dose IL-2 [interleukin 2] days, where you have patients go through a treatment and remain in CR off all drugs. That’s the best thing we can offer a patient. I’m really looking forward to seeing that data on the 3 I/O-TKI trials to make a determination about the durability. I know CR is not the most important one, but time off treatment may be a really important one for patients.

In terms of coming between these 3 TKIs, the patient matters, patient characteristics matter, disease characteristics matter, and drug characteristics matter. I’ve been a fan of cabozantinib-nivolumab in picking patients with bone disease. It goes back to prostate days. There was something about cabozantinib and what it does on bone disease. Through our experience with monotherapy TKI, when we just had sunitinib and pazopanib, the hardest group of patients to take care of were the patients with bone metastases. When the original cabozantinib data from METEOR came out, the response it had on bone disease was really impressive. You saw that with CheckMate 9ER as well. That combination also did well for patients with other sites of disease. If I see a patient with predominant bone disease, I’m definitely going to a cabozantinib-based combination.

Transcript Edited for Clarity