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Dr. Gerald Prager
“We think that liquid biopsies can help deliver the right treatment to a patient at the right time, and less invasively” than tissue biopsies, Dr. Prager said in a talk at the meeting. “They are useful for monitoring tumor growth and therapeutic activity.” He and his associates now have a study in progress evaluating the ability of serial ctDNA analysis to improve treatment with regorafenib in patients with metastatic colorectal cancer.
Analyses using ctDNA “are accurate, but we need to perform clinical trials to know what we should do with the information,” Dr. Prager said in an interview. “When we see a clone has been selected, should we change treatment before we see actual disease progression? This question has not yet been answered,” he said.
Circulating tumor cells
Liquid biopsy for CTCs has the advantage over ctDNA of having an FDA-approved test, which uses epithelial-marker antigens on the surface of CTCs to isolate the cells from a 7.5-mL specimen of blood. Study results showed a clear link between increased numbers of CTCs in patients and their rate of metastatic progression. For example, a meta-analysis published this year summarized data on CTC analysis in 1,944 patients with metastatic breast cancer evaluated in 20 separate studies done at 17 European centers. This meta-analysis showed that 47% of patients had a CTC count at baseline of 5 cells or more in a 7.5-mL specimen, and that this was significantly linked to diminished overall survival (hazard ratio, 1.92; 95% confidence interval, 1.73-2.14; P < .0001) (Lancet Oncol. 2014;15:406-14). The data also showed significantly reduced survival when CTC count increased either 3-5 weeks after treatment started or 6-8 weeks after treatment started. All these findings “confirm the independent, prognostic effect of CTC count on progression-free survival and overall survival,” the authors concluded.
Mitchel L. Zoler/Frontine Medical News
Dr. Michail Ignatiadis
This report confirmed the added value of CTC number, which was first reported using the same CellSearch technology a decade before (New Engl. J. Med. 2004;351:781-91).
The 2014 meta-analysis “provides level I evidence that CTC detection with CellSearch is an adverse prognostic factor in metastatic breast cancer,” said Dr. Michail Ignatiadis, an oncologist at the Jules Bordet Institute in Brussels.
But while CTC number “gives us very good prognostication, what we want is to know whether a treatment is working, and [whether we] can we get enough information from these cells to decide on what treatment to use. That is more challenging,” said Dr. Klaus Pantel, a professor of oncology and director of tumor biology at the University of Hamburg, Germany.
Mitchel L. Zoler/Frontine Medical News
Dr. Klaus Pantel
“We can now say, by monitoring CTCs in blood, whether or not treatment is going in the right direction; and it is important to have an early indicator of treatment response, but the challenge is to get a good picture” of the tumor to guide drug selection, Dr. Pantel said in an interview. He has recently used a new approach to collect CTCs developed by Gilupi that employs a receptor-coated needle placed in a patient’s blood vessel and left there for 30 minutes, during which roughly a liter of blood passes by the needle, allowing for collection of many more CTCs than is possible from a 7.5-mL specimen.
Another question about CTCs is that collection works well in metastatic-stage disease, when CTCs are relatively plentiful, but can it also play a role in assessing mortality risk in patients with early-stage cancer? Dr. Pantel and his associates recently addressed this question by using the CellSearch assay in 2,026 patients with early-stage breast cancer prior to treatment with adjuvant chemotherapy, and 1,492 patients after chemotherapy. The results showed that the presence of CTCs was linked to worse prognosis, with the worst outcomes occurring in women with 5 or more CTCs in 30 mL of blood (J. Natl. Cancer Inst. 2014;106:dju066 [doi: 10.1093/jnci/dju066]). The findings are the first “to provide strong evidence for the prognostic relevance of CTCs in early breast cancer before and after adjuvant chemotherapy in a large patient cohort,” Dr. Pantel and his coauthors concluded. “Our data offer support for the clinical potential of CTCs to assess the individual risk of patients at the time of primary diagnosis.”
Coupling liquid biopsies with better treatments
One of the challenges of using liquid biopsies to improve cancer treatment is the inherent limitation researchers often encounter of having to rely on inadequate treatment regimens with limited efficacy, Dr. Ignatiadis noted. That limitation came into play in a recent report of a study that used CTCs to stratify risk in patients with metastatic breast cancer and randomize them to either of two different treatment regimens. The results confirmed the prognostic significance of CTC number but failed to show that changing treatment based on CTC number improved outcomes, likely because the alternative regimen applied offered no real advantages over the comparator, the researchers concluded (J. Clin. Oncol. 2014 June 2 [doi: 10.1200/JCO.2014.56.2561]).