Transcript:Daniel Heng, MD, MPH, FRCPC: Hello, and thank you for joining this OncLive TV Peer Exchange. Today we are going to be talking about metastatic kidney cancer. With the availability of several approved targeted therapies for both first and second-line management of advanced renal cell carcinoma, patients are living longer than ever.

There are still unanswered questions, however, about the optimal way to sequence and combine the drugs that we have today, and more questions are arising as new and exciting therapies continue to emerge. In today’s discussion, we’ll reflect on the most recent information and how the new data relate to the way we practice.

I am Daniel Heng. I’m from the University of Calgary in Canada and chair of the Alberta GU Tumor Group, and a staff medical oncologist at the Tom Baker Cancer Center.

Today, joining me, are: Dr. Carlos Barrios of the Department of Medicine at the PUC School of Medicine in Brazil; Dr. Paul Nathan, a consultant medical oncologist at Mount Vernon Cancer Centre located in London, UK, specializing in the treatment of kidney cancer and melanoma; Dr. Susanne Osanto, a professor at the Department of Oncology for Leiden University Medical Center in Leiden, Netherlands; and Dr. Nizar Tannir, professor and deputy chairman for the Department of Genitourinary Medical Oncology, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center. Thank you, to each of you, for joining us today. Let’s get started.

Let’s begin by considering initial therapy for metastatic renal cell carcinoma. Paul, let’s start with you. What’s the best time to start targeted therapy?

Paul Nathan, MBBS, PhD, FRCP: I don’t think there’s one answer fits all to that question, so I think one has to consider the individual needs of the patient. Obviously, there are a group of patients who are symptomatic at presentation or who have disease that you know is going to threaten them in the short-term. And for those patients, there’s no doubt you’d want to treat them immediately and start as fast as you can.

With kidney cancer, however, there are a group of patients who have quite indolent disease, and, in the UK, we do, for those patients, try to identify them making a judgment on the pace of the disease and the location of the disease. And if somebody has got good performance status and small volume indolent disease, we would often watch and wait those patients until there’s significant progression of disease. And we know, from our local series, that we would often wait more than a year before starting treatment.

That algorithm may be influenced by the emergence of new immunotherapies, but for the moment that’s how we do it.

Daniel Heng, MD, MPH, FRCPC: Okay. So how do you choose your upfront therapy then? Do you use prognostic or predictive factors, at all?

Paul Nathan, MBBS, PhD, FRCP: I think our greatest driver is that clinical assessment of patient need, at presentation. I think the reality is that outside of clinical trials in clinical practice, one tends to be less driven by the formality of prognostic scoring systems. But we do tend to use lots of scoring systems locally, but there are obviously others, and I know you have lots of experience with others. What do you use in your practice?

Daniel Heng, MD, MPH, FRCPC: I use the IMDC criteria and that’s composed of six factors. Two are clinical, a Karnofsky performance status of less than 80%, diagnosis-to-treatment interval of less than one year, and four lab factors — anemia, thrombocytosis, neutrophilia, and hypercalcemia. So, I think for poor prognosis patients, we can use temsirolimus, but we can also use it, for example, for selecting patients for observation, as you talked about. So, for very favorable risk patients with one or two lesions, they could probably be monitored for a little while or even undergo metastasectomy.

But now, recently, we’re also using it for determining who has a good enough prognosis for a cytoreductive nephrectomy. So, for cytoreductive nephrectomies, if you have four or more of those factors, maybe your prognosis is not good enough to actually benefit from the cytoreductive nephrectomy. So I think that’s how we can sort of use the prognostic factors. So, for example, if you have lots of prognostic factors, six of them, maybe you should start targeted therapy right away and not get a cytoreductive nephrectomy.

Carlos H. Barrios, MD: Like Paul was saying, I’m very intrigued with this population of patients who have more indolent disease, that they may not require therapy initially. With all your experience looking at all these prognostic factors, any clues, from your perspective, in terms of where this patient population may lie?

Oligometastatic disease, like you were mentioning, and patients with good performance status, is there anything in your large database that can help us in that direction?

Daniel Heng, MD, MPH, FRCPC: I think it’s more about gestalt feel. And so we know that the favorable risk patients, you could potentially benefit from observation, but there are some favorable risk patients who need targeted therapy, as well, and there’s some intermediate patients you could observe as well, so it’s not perfect.

Susanne Osanto, MD, PhD: It’s maybe important to stipulate that those patients, I completely agree with you, that the clinical course of the disease in kidney cancer can be extremely indolent with patients even having large lung metastases that are stable over the years. But I think that it’s important to stipulate that those are not the patients who were entered into clinical trials, because the moment there’s a clinical trial, all the doctors are tempted to include those patients into the clinical trial. So I think that’s very important. The real world is different from patients in clinical trials.

Nizar M. Tannir, MD, FACP: I want to go back to the question that Paul was asked, about who are the patients whom you are comfortable following, observing through active surveillance, so to speak, without you having to initiate therapy. In our experience—and this was published by our group, as well as others—pancreatic metastasis is a signature of indolent disease, and I think patients who have oligometastases, as Carlos suggested, low volume, subcentimeter pulmonary disease, are patients who are not candidates for trials anyway because they don’t have measurable disease by the arbitrary system of RECIST. But endocrine metastasis, particularly, thyroid and pancreas, are signatures of indolent disease.

So when I look at the catalog of all the agents and therapies that we have available to treat our patients, and Susanne summarized it very nicely with an overview of all the therapies from interleukin-2 to bevacizumab/interferon to the VEGFR TKIs, let’s not forget that observation, surveillance is important. In our experience from MD Anderson, from our database, we had about 6% of patients whom we observed for many years, and these are patients whom we talked about having low volume metastases. So, when you look at who are you going to treat, and when do you initiate therapy, it’s about the tumor biology.

Patients who have poor risk, or are symptomatic, are patients who need to be treated. But also, it’s about the host, so let’s not forget that the host is important. Are we talking about a patient who is very elderly with comorbid illnesses where initiating therapy, even if it would be appropriate for another patient, would not be appropriate for that patient? So always, looking at the life expectancy of the patient has to come into the equation. So tumor biology and the host are very important.

Daniel Heng, MD, MPH, FRCPC: That’s a very good point because in the International MRCC Database Consortium, we see about 15% of patients actually aren’t treated with targeted therapy until after one year. And so there are a lot of people whom we choose to observe, but they’re carefully selected, carefully chosen.

Transcript Edited for Clarity