ASCO16: Liquid biopsy study reveals potential to guide treatment in advanced tumors

The findings of one of the largest genomic studies ever to be carried out in cancer demonstrate that genetic changes detected in blood samples strongly mirror those elucidated from traditional tumor biopsies.

The study, presented last weekend at the 2016 American Society of Clinical Oncology Annual Meeting (3–7th June 2016, IL, USA), involved analysis of blood samples from in excess of 15,000 cancer patients – a group representing over 50 tumor types. According to the authors, this is the largest study to use ctDNA analysis to select the appropriate targeted treatments for individual patients.

Identifying actionable targets in cancer currently relies upon analysis of tumor biopsies, isolated via surgery. As some patients can be too weak to undergo such biopsy procedures and owing to the difficulty of repeat procedures, there is widespread interest in harnessing circulating tumor DNA (ctDNA) within the blood to aid in making treatment decisions.

Specifically, this investigation involved 15,191 patients, of whom 37% had advanced lung cancer, 14% had breast cancer, 10% had colorectal cancer and the remaining 30% other cancers. Each of these patients provided one or more blood samples for ctDNA analysis.

ctDNA samples were analyzed for patterns of genomic change and then compared with available results of genetic testing of the tumor tissue in 398 patients. When key drivers of tumorigenesis – including abnormalities in EGFR, BRAF, KRAS, ALK, RET and ROS1 – were identified in ctDNA samples, they were also reported to be present in the tumor tissue 94–100% of the time.

Although tumor-driving alterations where present in the ctDNA samples at very low levels – half occurring at a frequency below 0.4% of the total DNA in circulation – the liquid biopsy assay employed remained accurate.

Additionally, the study assessed consistency in the frequencies of specific changes in ctDNA against previously published data from genomic analyses of tumor tissue, including data from The Cancer Genome Atlas. The findings suggest that liquid biopsy provides an accurate snapshot of the genomic landscape of the tumor.

The authors noted that frequently when ctDNA findings were not seen in tumor biopsies, the changes identified included detection of new genomic alterations associated with resistance to targeted cancer drugs, such as the EGFR T790M resistance mutations in patients on EGFR inhibitor therapy. The authors hypothesize that these alterations were absent in the tissue-based population data because those patients had yet to receive treatment.

These results allowed researchers to provide the study participants’ physicians with lists of possible treatment options, including US FDA-approved drugs and/or clinical trials. Overall, ctDNA testing revealed a possible treatment option for 63.6% of patients tested.

Clinical utility was evident among lung cancer patients. In 362 lung cancer cases, tissue was insufficient for testing or partially tested in 63%. Among these cases, the ctDNA test identified key genetic mutations at frequencies consistent with their prevalence in the published literature, providing these patients with their only source of an actionable target.

“These findings suggest that analysis of shed tumor DNA in patient blood, also known as a liquid biopsy, can be a highly informative, minimally-invasive alternative when a tissue biopsy is insufficient for genotyping or cannot be obtained safely,” commented study presenter Philip Mack of the University of California Davis Comprehensive Cancer Center. “Moreover, this test, known as Guardant360, provides an unparalleled opportunity to monitor changes in the cancer as it evolves over time, which can be critical when patients and physicians are discussing treatment options for continued tumor control.”

Following the positive results of this study, the team next plan to work on increasing the sensitivity of the assay to detect mutations at extremely low levels of ctDNA, which will make the test more sensitive for all solid cancer types in advanced stages and also aid in applying this technology to cancers in earlier stages.

Source: American Society of Clinical Oncology press release