As targeted therapies for cancer continue to shape the health care landscape, health care providers may increasingly utilize liquid biopsies to identify resistant to treatment.

During a session at the 36th Annual Chemotherapy Foundation Symposium, Joshua M. Bauml, MD, discussed how, despite the growing use of targeted therapy in patients with cancer, treatment resistance remains an inevitability. Although tissue biopsies are often considered the gold standard for testing genetic information to determine an mechanism of resistance, performing such tests repeatedly can prove invasive, painful, and unreliable.

“If a patient has a non-growing lymph node that I can easily biopsy, but the thing that’s growing or the evidence of their progression is a paracardiac lymph node that I cannot access, then doing a biopsy of that non-growing lymph node is very unlikely to tell me anything about the mechanism of resistance,” Dr. Bauml said. “We know that this resistance can occur in a heterogenous fashion.”

Liquid biopsies—testing DNA through plasma or urine rather than through tissue—offers health care providers an alternative method through they can evaluate potential treatment resistance, according to Dr. Bauml. Cell-free DNA can be found in plasma or urine, and testing these fluids is less invasive than performing tissue biopsies; indeed, this technology is already commonly utilized to detect fetal DNA in the blood of pregnant women

“We draw blood and request urine samples from our patients all the time, and the ability to test this serially is very appealing when we consider the fact that resistance develops over time,” he explained.

Highlighting the sensitivity of liquid biopsies, Dr. Bauml pointed to previous research in which the vast majority of patients who tested positive in one type of biopsy—tissue, plasma, or urine—tested positive in all of them. He acknowledged that the sensitivity of plasma and urine was not perfect (about 70%-80%), but added that larger tumor volumes tended to yield higher rates of positivity due to the higher amounts of cell-free DNA produced.

Additionally, Dr. Bauml noted that discordant results between different types of biopsies were possible. Although the majority of plasma-positive tests are also tissue-positive, there is an approximately 20%-30% chance that a plasma-negative test missed a resistance mutation that would have been caught by a tissue biopsy.

Dr. Bauml emphasized, however, that concordance between liquid and tissue biopsies was very high, with 85.7% of patients having a complete response or a partial response from data that came from plasma tests. Ultimately, he said, response rates didn’t matter based on where the diagnosis came from, and providers who find a target can act on it regardless of where it was found.

“Resistance must be closely monitored, but liquid biopsies can reliably identify alterations and have a clear role in the resistance setting,” Dr. Bauml concluded. “I would argue that they also have a clear role in a diagnostic setting for patients who do not have adequate tissue for molecular testing, and there is a lot of research being done in this space.”
 

Reference
  1. Bauml J. Plasma Genotyping in NSCLC.  Presented at: 36th Annual Chemotherapy Foundation Symposium. November 9, 2018. New York, New York.