ctDNA-Guided Treatment De-escalation Feasible in Advanced NSCLC

Circulating tumor DNA (ctDNA)-adaptive treatment de-escalation (decreasing amount of treatment to lessen toxicities) has been shown in a recent study to be a feasible tactic for treating some patients with advanced non-small cell lung cancer, as one expert explained in an interview with CURE®.

A study of 60 patients with advanced non-small cell lung cancer, findings of which were published in JAMA Oncology, found that, among patients with no radiologically detectable disease following treatment with tyrosine kinase inhibitors (TKIs) and local consolidative therapy (LCT), with median progression-free survival time (the time a patient lives without their disease spreading or worsening) of 18.4 months, 23% of patients required no additional TKI treatment. Additionally, 52% received intermittent TKI retreatment guided by ctDNA or carcinoembryonic antigen (CEA) prior to disease progression and 25% received TKI retreatment due to disease progression. The median total treatment break duration was 9.1 months, researchers reported.

LEARN MORE: ctDNA May Help Predict Lung Cancer Outcomes, Guide Treatment

“[The researchers] showed first [that treatment de-escalation] was feasible, and then potentially non-inferior to standard practice. And, again, what is our standard practice? Our standard practice is to continue therapy forever, and a ctDNA-tailored treatment or informed treatment break … could alleviate toxicities, and these toxicities can be both related to therapy, but also the economical burden of the therapy,” explained Dr. Valsamo Anagnostou, an assistant professor of oncology in the Sidney Kimmel Cancer Center at Johns Hopkins University School of Medicine.

Of note, some of the toxicities included mild (grade 1) to moderate (grade 2) rash, paronychia (nail inflammation from infection) and arrhythmia (irregular heart rate or rhythm).

ctDNA, as defined by the National Cancer Institute, is made up of small pieces of DNA that are released into a patient’s bloodstream by tumor cells, and a sample of blood can be used to look for, measure, and identify specific mutations in the DNA. CEA, a type of tumor marker, may be found in the blood of people with some cancers and other diseases and those who smoke tobacco and may be able to help track the efficacy of cancer treatments or if a disease has returned, the National Cancer Institute explained.

TKIs, a type of targeted therapy, block the action of enzymes called tyrosine kinases that are involved in cell signaling, growth and division and may be too active or found in high levels in some cancers, according to the National Cancer Institute.

In the study, patients who remained in TKI cessation had a median treatment break of 20.3 months, while those who received retreatment due to detectable ctDNA and/or CEA had a median progression-free survival of 20.2 months and a median treatment break of 8.8 months and those who underwent TKI retreatment due to progressive disease had a median progression-free survival of 5.5 months, researchers reported.

Among all patients, there was a 96% TKI response rate and a median time until the next treatment of 29.3 months.

“The findings of this nonrandomized controlled trial provide valuable information regarding the potential utility of planned adaptive de-escalation therapy in the treatment of patients with advanced NSCLC,” the researchers wrote. “The use of reliable ctDNA-based assays enables the accurate monitoring of patient status after systemic therapy and LCT.”

“This is intuitive, but what they found was confirmatory of a hypothesis, if you will,” said Anagnostou. “And an important point that they're making is that the clinical efficacy of targeted therapy was not compromised in patients that went on a retreatment break. In other words, patients that went on a break — and the break may have lasted for some patients for a long period of time, 20 months or whatnot — when they restarted the targeted therapy, it was very, very effective with a great response rate.”

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