The Impact of Neoadjuvant Therapy on Treatment Selection in Advanced RCC


Dr Ornstein describes how the choice of neoadjuvant therapy can impact subsequent treatment selection in advanced RCC.

Tian Zhang, MD: Dr Ornstein, I’d love to hear your thoughts about how the use of neoadjuvant therapy might impact our subsequent therapy choices and timing and how we’re going to be separating treatment sequences.

Moshe C. Ornstein, MD, MA: That’s a great question. The first thing to keep in mind is that whereas adjuvant pembrolizumab is FDA approved, most of the investigations in the neoadjuvant setting are still just that—they’re investigational. A lot of us in our clinics have been using this for years. Let’s say we have a patient who has a solitary kidney, and we’re hoping to spare some nephrons and avoid having that patient be dialysis dependent after a nephrectomy, trying to make a partial nephrectomy a little easier in a patient who essentially has localized tumor.

What’s been helpful with this study that was just presented is that previously the data were predominantly with VEGF TKIs [tyrosine kinase inhibitors—crizotinib, axitinib, etc. This tells us, maybe more than the efficacy, that this approach is at least safe and that the patients are getting to surgery and getting through surgery OK. I wouldn’t say necessarily that this is a practice-changing trial. It has to be case by case. But it comforts those of us who do this in practice in an effort to spare some nephrons at the time of nephrectomy in the right patient—the solitary kidney, essentially localized tumor, etc—in close collaboration with the urologist telling us that this is safe. There’s some efficacy in terms of tumor burden shrinkage.

That said, it’s hard to say how this plays a role in systemic therapy. The overwhelming majority of patients don’t have disease progression within 3 months of surgery. That’s a real minority. What’s going to happen—this gets back to what Dr [David] Braun was saying, in terms of taking a play out of the cisplatin-refractory lung cancer–bladder cancer space—is that most of these patients will have the therapy washed out of their system by the time the cancer progresses. Adjuvant pembrolizumab is likely to impact frontline therapy in the metastatic setting, but I don’t think neoadjuvant therapy is likely to impact it in the same way.

This transcript has been edited for clarity.

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