ASCO Annual Meeting
ASCO Annual Meeting
Perspective from Sumanta K. Pal, MD
Perspective from David M. Nanus, MD
June 04, 2016
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Liquid biopsy assay exhibits efficacy similar to traditional tumor biopsy

Perspective from Sumanta K. Pal, MD
Perspective from David M. Nanus, MD
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CHICAGO — Liquid biopsy identified genomic alterations in patients with advanced solid tumors at a similar rate to traditional tumor biopsy, according to data presented at the ASCO Annual Meeting.

Information gleaned through liquid biopsy may be feasibly used to aid in treatment decision-making, results showed.

Philip Mack

Philip Mack

“There is a real need for improved comprehensive tumor genetic profiling that will allow us to use more appropriate targeted therapies based on the molecular makeup of tumors,” Philip Mack, PhD, professor and director of molecular pharmacology at University of California Davis Comprehensive Cancer Center, said at a press conference. “It has been known for decades that advanced cancers shed tumor DNA into the bloodstream. These DNA harbor all the same cancer-associated mutations of potential use in diagnostics, which we commonly term nowadays as precision therapeutics.”

The use of next-generation sequencing of circulating tumor DNA (ctDNA) has enabled the noninvasive profiling of solid tumor cancers. However, studies of liquid biopsies to date have been conducted in modest cohorts.

Mack and colleagues determined the somatic genomic profiles of 15,191 patients with advanced cancer by using a deep-coverage ctDNA next-generation sequencing test targeting 70 genes (Guardant360, Guardant Health).

The cohort consisted of patients with lung cancer (37%), breast cancer (14%), colorectal cancer (10%) and other solid tumor cancers (39%).

They compared the frequency of somatic alterations per gene to those previously described in tissue sequencing projects, such as The Cancer Genome Atlas, with the accuracy of screening assessed through a comparison of matched tissue tests from 398 patients.

The clinical sensitivity of ctDNA was 86% for patients with lung cancer, 83% for patients with breast cancer, 85% for patients with colorectal cancer and 78% for patients with other cancers.

When researchers detected key abnormalities in EGFR, BRAF, KRAS, ALT, RET and ROS1 in ctDNA, the likelihood of the same mutations being found in tumor tissue ranged from 94% to 100%.

Mutation frequencies correlated well between ctDNA and published tissue data for TP53 (r = 0.94), KRAS (r = 0.99) and PIK3CA (r = 0.99).

The overall accuracy of ctDNA sequencing, when compared with matched tissue tests, was 87% (n = 336). Accuracy increased to 98% when blood and tumor sample collection occurred less than 6 months apart.

The use of ctDNA data identified potential treatment options in 85% of patients, 49% of whom were found to harbor mutations useful as biomarkers for FDA–approved targeted therapies.

The researchers reported four distinct classes of clinical outcome benefits observed through liquid biopsy:

actionable mutations in cases with insufficient tissue quality, including ALK fusions and EGFR or BRAF activating mutations in lung cancer, and ERBB2 amplification in gastric cancer;

actionable resistance mutations at the time of progression, including MET amplification or EGFR T790M in lung cancer;

the evolution of sensitivity upon progression in ERBB2–amplified, metastatic triple-negative breast cancer; and

undergenotyped tumors in lung cancer with BRAF V600E or ERBB2 insertion or deletion.

The researchers intend to increase the sensitivity of the assay in order to detect mutations at extremely low levels of ctDNA, which may allow the test to be used on patients with earlier-stage cancers.

“The advantages of plasma testing are numerous when compared with tissue biopsy,” Mack said. “It is easy to do in the clinic, with a simple blood draw that avoids all biopsy-related complications. It allows physicians to monitor changes in the genetics of disease over time as it evolves. And it provides an opportunity to identify treatment-induced resistance mechanisms.” – by Cameron Kelsall

Reference:

Zill OA, et al. Abstract LBA11501. Presented at: ASCO Annual Meeting; June 3-7, 2016; Chicago.

Disclosure: Guardant Health funded this study. Mack reports honoraria and travel expenses from Guardant Health; consultant roles with Apton Biosystems, AstraZeneca, MolecularMD and Novartis; and research funding from Boehringer Ingelheim. Please see the abstract for a list of all other researchers’ relevant financial disclosures.