cfDNA Proves Accurate Yet Faster Than Tissue Genotyping in NSCLC Biomarker Identification

A liquid biopsy test detected all of the guideline-recommended biomarkers in newly diagnosed patients with metastatic non-small cell lung cancer (NSCLC) at a similar rate but faster turnaround time to that of tissue genotyping, according to data presented during a media preview of the AACR Annual Meeting 2019, to be held March 29-April 3, in Atlanta.

In turn, nurses play a key role in helping patients to understand why these tests are safe, effective, and faster in determining treatment options, according to study investigator Vassiliki Papadimitrakopoulou, MD, professor of medicine, Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center in Houston.

“Nurses are the pillars of every medical oncologists’ practice,” she said in an interview with Oncology Nursing News^Ò ahead of the presscast. “In reality, they are the ones talking to patients about day-to-day issues. Nurses have a big role to play in explaining to the patients what this test does and how easy it is to get and avoid delays and potential invasive harm to the patients.”

In particular, it is important for nurses to explain why tissue biopsies are still the standard in diagnosing NSCLC, while liquid biopsies can identify biomarkers to guide treatment decisions. “Explaining those differences to the patients when they first come in with a new diagnosis of lung cancer is very important, and repetition of the message is very important,” Papadimitrakopoulou added.

The prospective, multicenter Noninvasive versus Invasive Lung Evaluation (NILE) study evaluated whether Guardant360 can be used to detect all 7 guideline-recommended predictive biomarker mutations (EGFR, ALK, ROS1, BRAF, RET, MET, and ERBB2) and 1 prognostic biomarker mutation (KRAS) at the same rate as traditional tissue genotyping tests in 282 patients with newly diagnosed advanced NSCLC enrolled at 28 North American centers between July 2016 to April 2018.

Of the 282 patients who submitted a pre-treatment blood sample for cell-free (cf) DNA analysis, the majority were white (81.9%) and half were female (54.3%).

Guardant360¾a 73-gene next generation sequencing panel¾increased the rate of biomarker detection by 48%, from 60 patients identified with at least 1 guideline-recommended biomarker using tissue-based tests alone to 77 patients with the liquid biopsy (21.3% versus 27.3%; P < .0001). This included patients whose samples were negative by tissue (n = 7), not tested (n = 16), or did not have enough material (n = 6) for the tissue-based tests, according to study results that were presented during a media preview of the AACR Annual Meeting 2019, to be held March 29-April 3, in Atlanta.

Of the 193 patients without a guideline-recommended biomarker by tissue or liquid biopsy, 24 (12.4%) had an activating KRAS alteration identified in tissue alone (n = 3) or concordant with cell-free (cf) DNA (n = 21), increasing the number of KRAS-positive patients from 24 to 92. This included 3 with negative tissue biopsies, 60 not assessed, and 5 who did not have enough tissue material.

The investigators noted liquid biopsy testing rescued 30.2% (n = 85) of patients, including those who did not have enough tissue material and those who were incompletely genotyped or negative for the biomarker in tissue.

“The downside of obtaining mutations from tissue biopsies is that usually if this testing is not done with a very powerful and comprehensive assay, such as next-generation sequencing, it is done in successive steps: one test after another, which frequently leads to depletion of the tissue sample,” Papadimitrakopoulou explained. “Therefore, you end up with testing that is not complete because the tissue is not enough for testing of all the biomarkers.”

In addition, the study found a positive-predictive value of 100% for EGFR, ALK, ROS1, and BRAF mutations, for which there are agents already approved to treat this patient population.

Time from test order to final results was a median 9 days with Guardant360 compared with 15 days with tissue-based testing.

The researchers acknowledged the study was limited by its comparison of liquid biopsy testing to a current standard-of-care tissue genotyping test and not the tissue-based next-generation sequencing test, adding “the study results are only applicable to the Guardant360 test and not other liquid biopsy tests,” according to an AACR press release.

Papadimitrakopoulou concluded the study validates the clinical utility of cfDNA in newly diagnosed metastatic NSCLC. “What prompted the study was the desire to demonstrate that the liquid biopsy, which is easier to obtain and with a faster turnaround time, can detect these mutations and alterations in the DNA at a rate similar to the standard, which is tissue biopsy. That is something that is assumed to be true but was not tested in a clinical trial prospectively,” she added. “We felt there was a need for this since the desire to expand the group of patients who get these tests upfront is great. Having a test that we can rely upon to get good results for treatment choices is a very important step.”

Reference:

Leighl N, Page RD, Raymond VM, et al. Clinical utility of comprehensive cell-free DNA (cfDNA) analysis to identify genomic biomarkers in newly diagnosed metastatic non-small cell lung cancer (mNSCLC). Presented at: AACR Annual Meeting 2019 media preview; Feb. 27, 2019; Philadelphia.