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Dr. Alan Tan explores circulating tumor DNA, its role in clinical trials and its potential impact on patients with renal cell carcinoma.
Circulating tumor DNA (ctDNA) is not yet standard practice in the clinical for patients with metastatic renal cell carcinoma (mRCC), but it may provide reassurance and has the potential to offer patients peace of mind, according to Dr. Alan Tan.
“[There’s] just more peace of mind for the patient [if we can say], ‘Hey, we're detecting things at the molecular level.’ We don't necessarily need to wait until the cancer comes back at a solid tumor, radiographic progression,” he explained in an interview with CURE®.
Tan is a genitourinary oncology (GU) and melanoma specialist at the Vanderbilt-Ingram Cancer Center in Nashville, Tennessee. He also serves as an associate professor of medicine in the Division of Hematology and Oncology at Vanderbilt University Medical Center and GU Executive Officer with the Alliance for Clinical Trials in Oncology.
Tyrosine kinase inhibitor: a type of medication that blocks the activity of enzymes called tyrosine kinases.
Partial response: a decrease in the size of a tumor or the extent of cancer in the body in response to treatment.
Complete response: the disappearance of all signs of cancer in response to treatment.
Overall survival: the time that a patient lives, regardless of disease status.
ctDNA, as defined by the National Cancer Institute, is used to refer to small pieces of DNA that are released into a patient’s blood by tumor cells after they die. A sample of blood can be utilized to look for and measure the amount of ctDNA and identify specific mutations in the DNA.
Tan was among a team of researchers who determined that, among patients with mRCC, serial tumor-informed ctDNA negativity or clearance was associated with improved outcomes when compared with patients who became or were persistently ctDNA positive. Notably, these findings were published in JCO Precision Oncology.
[ctDNA] is still a topic that not everybody's bought into right now. This is one of my research interests. I don't think this is something that you should go and tell your doctor, "You have to do this," or "You should do this" [because] I don't think this is the norm. It's not something that should be expected to be done; however it is out there. It is commercially available. It can be intriguing to follow for the purposes that I've mentioned, but just be cautious, because even though these data are compelling, we really do need to study this in a more controlled fashion.
In fact, at Vanderbilt here, we have designed a clinical trial ... [where] we're running a cohort of about 30 patients to test this pilot out, to see if we can de-escalate treatment in patients that are on a combination of [Opdivo (nivolumab)] plus [Cabometyx (cabozantinib}]. If we commit down this route, we think that [for] people that take a [tyrosine kinase inhibitor (TKI)] such as [Cabometyx], this is more of a long game, they're never going to get off these TKIs forever. We know that from other studies, like the STAR study — and there was a European study that that looked at intermittent TKI dosing — that it is feasible for people that had good responses, [whether that be] partial or complete responses, they could stop these TKIs. [This would give] them their quality of life back without compromising their efficacy or their overall survival.
We are using ctDNA to inform us more on how this could be done safely. Not only are we using imaging, but we’re also incorporating ctDNA in these patients, they'll get a six-month lead in for the [immunotherapy] TKI — in this case, [Opdivo] plus [Cabometyx]. And if at baseline, they're ctDNA positive, and then at six months later, they have undetectable ctDNA, plus they also have at least a partial response on their CT scans, they are eligible to stop their TKI treatment and just monitor their DNA levels every four weeks or so. And if it reemerges, that would be a prompt to perhaps go back on the treatment. So, just more peace of mind for the patient that, hey, we're detecting things at the molecular level. We don't necessarily need to wait until the cancer comes back at a solid tumor, radiographic progression.
Transcript has been edited for clarity and conciseness.
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