Panelists: Robert A. Figlin, MD, Cedars-Sinai Medical Center; Thai H. Ho, MD, PhD, Mayo Clinic Arizona; Martin H. Voss, MD, Memorial Sloan Kettering Cancer Center; Michael B. Atkins, MD, Georgetown Lombardi Comprehensive Cancer Center; Sandy Srinivas, MD, Stanford University Medical Center
Robert A. Figlin, MD: In clinical trials, we are always given very specific criteria to stop treatment. In clinical practice, we see patients who have disease progression that, in a clinical trial, might result in changing therapy. But, they are tolerating therapy well. They are not developing new sites of disease. How do you make the decision about when to switch from first-line therapy? What are those criteria that you think matter for our practicing colleagues?
Martin H. Voss, MD: That’s an important question. One of the shortcomings of how we make these decisions on clinical trials is that we are bound to whatever algorithms are set forth in the protocol, and often, we have to take patients off treatment although the patient and the treating investigator may not want to. In clinical practice, we have a lot more freedom to do whatever we choose.
I think there are a couple of paradigms, that everyone would agree upon, that determine if an agent should be switched. One of them, certainly, is the development of newly symptomatic disease. If patients develop new symptoms, or worsening symptoms, in the setting of disease progression—be it small in radiographic exams, or large—that, to me, is an indication to change study treatment. One can also integrate the tolerance of therapy, so it’s keeping that balance of having a patient stay on treatment as long as we feel that their quality of life is preserved and ensuring that the disease is controlled radiographically.
I personally do not do RECIST assessments outside of clinical trials. Few colleagues do. I don’t do the millimeter measurement subscore analyses for my patients who I treat outside of a trial. I look for a change in the pace of the growth if I keep patients on a treatment despite a slow growth. I watch, very closely, whether the pace of that increase goes up with future scans. I look for the emergence of newly metastatic disease in organs that were not previously involved. That, to me, is an indication to switch. And, like I said before, I look for new symptoms related to the disease progression. Some of this differs, now, from which type of agents you use. With tyrosine kinase inhibitor therapy, one might approach that very differently than with immunotherapy—when we think about interpreting radiographics and the dynamics of treatment response differently.
Robert A. Figlin, MD: Michael, do you have some thoughts on this?
Michael B. Atkins, MD: Yes. I think things have changed a little bit with regard to when to switch in the first-line setting—with, now, 10 different drugs approved. And if someone has disease that’s growing, or if they’re not tolerating the first-line treatment, you’ve been forced to lower the dose. And then, because you’ve lowered the dose, their disease is no longer responding to therapy. I think that there’s a quicker sense to try to switch to a second-line therapy because, as I said before, we have better second-line treatments than first-line treatments. And so, moving to nivolumab as an approved second-line therapy after someone who’s clearly not going to get a major response anymore to a VEGF inhibitor is something that I think a lot of us do. We also know that for patients who have responded to a VEGF inhibitor and then have started to become resistant, if you give them a break from that, they can become sensitive again. So, giving them a break may also be useful if they don’t end up responding to the immunotherapy. When we used to have only 1 or 2 approved drugs, you wanted to give it for as long as possible. But now that there are other drugs, I think you individualize that decision. I think people are quicker to look at second-line therapies than they might have been before.
Robert A. Figlin, MD: Thai, around first-line approaches—before we talk about what decisions we have about going to second-line therapy—are there any special situations? We talk about metastasectomies. We obviously are using radiation therapy appropriately. What’s happening to our patients with brain disease is dramatically different than it was decades ago because of the availability of the Gamma Knife procedure. We know that some of the drugs that we give actually can control some of the central nervous system symptoms, and also, there’s still this drug, temsirolimus, that’s out there that has been approved in the frontline setting, that many of us would think about not using absent of some next-generation sequencing abnormality in the PI3K–mTOR pathway. Are there any special situations that our colleagues need to know about, that you think about, when treating in the frontline setting?
Thai H. Ho, MD, PhD: When I think about it in the frontline setting, I look at the burden of disease. I still think there’s a role for surgical consolidation. That’s something that Mayo Clinic surgeons have always been very aggressive about. Often, you may have a patient with oligometastatic disease, and if you can achieve control in oligometastatic disease, I talk to the patients about a potential for surgical consolidation. There are also certain subsets of patients who seem to have more of an indolent disease, such as patients with pancreatic metastases. It’s rare for a lot of tumors to go to the pancreas, but kidney cancer is one of those. And that particular patient population seems to have a little bit more of an indolent disease than patients without pancreatic metastases.
Robert A. Figlin, MD: In my own practice—having treated kidney cancer patients now, like Michael, for decades—it’s only as the patient survives longer that you see the metastatic disease in the pancreas. Our successes have led to some unusual new presentations.