Perspectives on Metastatic Kidney Cancer - Episode 12
Transcript:Nizar M. Tannir, MD, FACP: Danny, I think it’s important to bring up whether there is a biomarker to select [patients]. As we discussed earlier, there is no biomarker to select for the targeted agents. So there was hope that with the immune checkpoint inhibitors, that we will have one. We thought we had a biomarker with PD-L1 expression, but what this phase III trial, CheckMate 025, showed is that the PD-L1 expression in tumor cells, whether you use a 1% cutoff or a 5% cutoff, is not associated with a benefit. So we’re back to the drawing board as to what the biomarker is for selection of patients for an immune checkpoint inhibitor. Right now, I do not think we have that, so any patient should be eligible to receive nivolumab. You cannot segregate patients based on a PD-L1 expression, positive or negative.
Carlos H. Barrios, MD: But Nizar, correct me if I’m wrong, that these patients were tested in the initial tumor. We know PD-L1 is a very dynamic marker, so who cares what the PD-L1 is in the primary tumor? I do care for the PD-L1 status when I’m starting therapy. We lack that information completely.
Susanne Osanto, MD, PhD: Yeah, but maybe that is even not informative and then we’re still stuck with the fact that we do not have...
Carlos H. Barrios, MD: Definitely.
Daniel Heng, MD, MPH, FRCPC: I think that’s a difference between RCC and melanoma. In melanoma, you can biopsy the skin and that’s fairly straightforward.
Paul Nathan, MBBS, PhD, FRCP: But the similarity is that we don’t have a validated predictive marker.
Carlos H. Barrios, MD: We don’t have the marker.
Paul Nathan, MBBS, PhD, FRCP: And, even in lung cancer, where there’s development of PD-L1 expression as a biomarker, the reality is that it’s become a cost-effectiveness enrichment tool. It’s not an adequate clinical selection tool. So no clinician, in my view, should treat somebody with lung cancer on the basis of whether or not they’ve got PD-L1 expression. Health economically, you can enrich a population of patients who are going to have a higher chance of benefit, but it’s nowhere near good enough to be called a clinical predictive tool.
Nizar M. Tannir, MD, FACP: It’s not like EGFR, using an immune checkpoint inhibitor in lung cancer—or KRAS with colorectal cancer and the choice of the antibody you pick.
Susanne Osanto, MD, PhD: I’m not sure that when both cabozantinib and nivolumab are going to be approved by FDA, EMA, and all the other regulatory authorities—with current hype around nivolumab—whether that is really going to be the winner because we’re going to over treat 80% of patients and we do not have a good selective marker; and it’s an IV treatment, so it adds a lot of stress in your hospitals. Of course, I’m extremely enthusiastic. I loved the presentation. You love the publication, but I’m not really sure whether it’s going to be implemented as easy as that. And then on top of this, of course, it’s extremely costly. So, if the price doesn’t go down or we don’t have another way of agreement with pharma to say, well, you can only get reimbursement if the treatment proves to be effective in Mr. X or Mrs. Y, I’m not 100% sure that it’s going to be that same hype and rush to treat all your patients with nivolumab in the second line.
Nizar M. Tannir, MD, FACP: Danny, in the US, I’ve spoken to a lot of my colleagues and we have a lot of ad boards about choice of second-line therapy; whether it be nivolumab, cabozantinib, or axitinib; everolimus is pushed down to the fifth-line and possibly, axitinib, also to the fourth-line if cabozantinib is FDA-approved pretty soon. But I agree with Susanne, I think cost is an important question, especially in countries where you don’t have all the resources. So I think if the METEOR trial showed a survival advantage, overall survival (OS) now is the secondary endpoint, and if it shows significant survival difference for cabozantinib and everolimus, then you’re going to have a drug that has a progression-free survival advantage, OS advantage, response rate advantage, that’s oral, and that’s going to be cheaper when you use an oral agent, rather than bringing the patient in every two weeks to the clinic for nivolumab. So I think, even in the US, I would not be surprised if people went to cabozantinib, as the salvage therapy, after the first-line VEGFR TKI instead of nivolumab, despite the exciting news about immune checkpoint inhibitors, because of convenience of an oral agent; and the cost is going to be less with an oral agent rather than doing the IV therapy every two weeks.
Daniel Heng, MD, MPH, FRCPC: I completely agree with that.
Transcript Edited for Clarity