In an exploratory analysis of 50 patients, researchers followed treatment response with ddPCR analysis.

“Patients whose blood tests showed a disappearance of the mutations were least likely to discontinue therapy,” Dr Sacher said.


Continue Reading

Given the compelling data, researchers are planning to offer this approach to all patients with advanced NSCLC at the Brigham and Women’s Hospital in Boston, MA. Dr Oxnard indicated that a treatment trial is also in the planning stages. Briefly, treatment will be offered based on positive-ddPCR tests. For patients who test negative, treatment will be offered based on genotyping tissue biopsies. 

Dr Oxnard pointed out that other ddPCR tests are commercially available, but this validated one developed internally is not available elsewhere.

“We need to demand validated tests from commercial companies,” Dr. Oxnard stressed. “This study provides a clinical validation of the ddPCR test,” he added.

However, the ddPCR does not pick up copy number alterations and rearrangements and will, therefore, not detect alterations in ALK or ROS1, both of which can be treated with available targeted therapy.

Other platforms will need to be used to provide this information, Dr Sacher indicated. He was referring to next-generation sequencing (NGS) that is commercially available. “However, the platforms used in NGS are more complex and may sacrifice sensitivity and speed,” Dr Sacher said.

“Broadening the capabilities [of ddPCR] to ascertain not only point mutations (single nucleotide variants) but also copy number variants (amplification) and activation gene fusions while minimizing false-positive results is a goal that hopefully will be reached in the near future,” the editorialists wrote.

The editorialists pointed out that there is no agreement on comparisons between different platforms and laboratories. Along with a requirement of accurate quantitation, these issues need to be resolved.

RELATED: Crizotinib Effective for NSCLC Brain Metastases

Advances in liquid biopsies “will allow appropriate treatments to be delivered faster, with less risk to patients, and will allow detection of molecular abnormalities that may be missed by a biopsy (sampling error),” the editorialists indicated.

“In addition, such methods would allow more frequent sampling for detection of response, or resistance, and facilitate additional research to develop and optimize new cancer treatments,” they concluded.

References

  1. Sacher A, Paweletz C, Dahlberg SE, et al. Prospective validation of rapid plasma genotyping for the detection of EGFR and KRAS mutations in advanced lung cancer. [published online April 7, 2016]. JAMA Oncol. doi:10.1001/jamaoncol.2016.0173.
  2. Williams PM, Conley BA. Clinical application of liquid biopsies. [published online April 7, 2016]. JAMA Oncol. doi:10.1001/jamaoncol.2016.0240.