Liquid Biopsies: An Emerging and Versatile Monitoring Modality in Lung Cancer

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Liquid biopsies identify circulating tumor DNA in the urine and plasma of patients with cancer.
Liquid biopsies identify circulating tumor DNA in the urine and plasma of patients with cancer.
The following article features coverage from the Chemotherapy Foundation Symposium (CFS) in New York, NY. Click here to read more of Cancer Therapy Advisor's conference coverage.

At the 35th Annual Chemotherapy Foundation Symposium, Joshua Bauml, MD, gave an oral presentation describing how to best integrate liquid biopsies into the management of lung cancer and how it may become standard protocol in future treatment modalities.1

The use of targeted genomic therapies among patients with genetic mutations significantly prolongs median overall survival; in a study by Kris and colleagues published in the Journal of the American Medical Association in 2014, patients with genetic aberrations treated with targeted therapies achieved median OS of 3.49 years compared with 2.38 years and 2.08 years among patients with genetic aberrations not treated with targeted therapies and patients without aberrations and not treated with targeted therapies, respectively.2

However, resistance is inevitable and happens in a highly heterogeneous manner. It is critical to evaluate the resistance mechanisms so appropriate treatment can be administered.

At initial diagnosis most patients undergo biopsy, but many patients experience symptomatic progression that require repeated tissue biopsies. Dr Bauml stated that there are many difficulties with this strategy, such as patient and provider hesitance due to adverse events, complex scheduling, pain, and tissue accessibility. Furthermore, a sample collected from 1 biopsy site may not even contain the mechanism responsible for resistance.

A new method of mutation identification is liquid biopsy. Liquid biopsies identify circulating tumor DNA in the urine and plasma of patients with cancer, and are highly appealing because they are minimally invasive and may be used in serial testing. Testing can be targeted or comprehensive by performing next generation sequencing across a wide variety of genetic aberrations.

Two major analyses have been performed in patients with T790M mutation-positive disease to determine the sensitivity of liquid biopsies. Evidence from the studies demonstrated that the majority of patients that were positive by 1 assay were found to be positive by all other methods. The sensitivity of plasma and urine testing ranged from 70% to 80%. Researchers also discovered that regardless of the source of mutation DNA, the response rate, duration of response, and progression-free survival remained consistent among patients in the study.

However, disparate results may occur. Dr Bauml stated that if the patient has plasma-positive disease, plasma biopsy results are reliable. In the instance of plasma-negative disease however, tissue biopsies are critical and should be performed. Liquid biopsies have very high positive predictive value, but the value of a negative test is more limited.

Potential future applications of liquid biopsies include the diagnosis of metastatic disease, serial monitoring of patients on therapy instead of utilizing scans, and may even be used to assess minimum residual disease after surgery.

Dr Bauml concluded, “[t]argeted therapies really change the landscapes of different patient subsets but resistance must be closely monitored throughout treatment. Liquid biopsies are able to reliably identify genetic aberrations in lung cancer, but there are data in other tumors as well.”

Read more of Cancer Therapy Advisor's coverage of the Chemotherapy Foundation Symposium (CFS) by visiting the conference page.

References

  1. Bauml J. Liquid biopsies to improve patient flow in lung cancer.  Oral presentation at: 35th Annual Chemotherapy Foundation Symposium. November 8-10, 2017; New York, New York.
  2. Kris MG, Johnson BE, Berry LD, et al. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA. 2014;311(19):1998-2006. doi: 10.1001/jama.2014.3741
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