CTCs Could Shorten Drug Trials
16 April 2015
Cancer Discovery
As cancer progresses, tumor cells dissociate and enter the bloodstream. Considered a “liquid biopsy,” these circulating tumor cells (CTC) can show how a patient's cancer evolves and responds to treatments. A recent study highlights a new prognostic utility: Combined with another blood marker, CTC counts could serve as a surrogate predictor of survival, according to a phase III trial in metastatic castration-resistant prostate cancer.
Surrogate measures are sorely needed. So many therapies have proven effective for advanced prostate cancer that it's hard for trials of new drugs to show a survival benefit, running the risk that effective therapies may not get approved. “You'd like to get drugs approved faster,” says the study's lead author Howard Scher, MD, chief of the genitourinary oncology service at Memorial Sloan Kettering Cancer Center in New York, NY.
Disease progression can be tracked by PSA tests, and bone scans can reveal if cancer has spread. However, PSA changes can be misleading, and bone scans cannot detect short-term treatment responses.
Some scientists think changes in CTC count could be a more reliable biomarker. Prior studies suggest that measuring CTCs has the potential to predict survival and guide therapy in metastatic breast cancer. Although researchers have developed various approaches to pick out these rare cells, only Janssen Diagnostics' CellSearch is FDA-cleared.
In the new study, Scher and colleagues used this assay to count blood-borne CTCs in 711 men with metastatic prostate cancer in a multinational phase III trial of abiraterone (Zytiga; Janssen). The researchers measured the participants' CTCs, as well as other blood biomarkers, at baseline and at 4, 8, and 12 weeks.
Patients who received abiraterone plus prednisone survived 17.7 months, versus 15.1 months for the control group on prednisone alone. More importantly, when participants were stratified into low-, intermediate-, and high-risk groups based on CTC counts and blood levels of the enzyme lactate dehydrogenase (LDH), their 12-week risk classification predicted their outcome, regardless of treatment. Overall 46% of low-risk patients survived 2 years, whereas only 2% of participants classified as high-risk were alive at this same time point.
The study suggests that “CTCs could well permit us to get ‘red light/green light’ answers for new drugs faster and more efficiently,” says Daniel Hayes, MD, of the University of Michigan Comprehensive Cancer Center in Ann Arbor. Hayes invented the CellSearch CTC capture technology but was not involved with the current study.
Future CTC-based approaches could also help identify which treatments are likely to work in individual patients. However, “that will require going beyond counting CTCs and providing more detailed molecular information, such as whether [patients] have acquired new mutations or have expression patterns that predict resistance or sensitivity to particular therapies,” says Daniel Haber, MD, PhD, a cancer geneticist at Massachusetts General Hospital, Boston, who did not take part in the research.
16 April 2015
Cancer Discovery
As cancer progresses, tumor cells dissociate and enter the bloodstream. Considered a “liquid biopsy,” these circulating tumor cells (CTC) can show how a patient's cancer evolves and responds to treatments. A recent study highlights a new prognostic utility: Combined with another blood marker, CTC counts could serve as a surrogate predictor of survival, according to a phase III trial in metastatic castration-resistant prostate cancer.
Surrogate measures are sorely needed. So many therapies have proven effective for advanced prostate cancer that it's hard for trials of new drugs to show a survival benefit, running the risk that effective therapies may not get approved. “You'd like to get drugs approved faster,” says the study's lead author Howard Scher, MD, chief of the genitourinary oncology service at Memorial Sloan Kettering Cancer Center in New York, NY.
Disease progression can be tracked by PSA tests, and bone scans can reveal if cancer has spread. However, PSA changes can be misleading, and bone scans cannot detect short-term treatment responses.
Some scientists think changes in CTC count could be a more reliable biomarker. Prior studies suggest that measuring CTCs has the potential to predict survival and guide therapy in metastatic breast cancer. Although researchers have developed various approaches to pick out these rare cells, only Janssen Diagnostics' CellSearch is FDA-cleared.
In the new study, Scher and colleagues used this assay to count blood-borne CTCs in 711 men with metastatic prostate cancer in a multinational phase III trial of abiraterone (Zytiga; Janssen). The researchers measured the participants' CTCs, as well as other blood biomarkers, at baseline and at 4, 8, and 12 weeks.
Patients who received abiraterone plus prednisone survived 17.7 months, versus 15.1 months for the control group on prednisone alone. More importantly, when participants were stratified into low-, intermediate-, and high-risk groups based on CTC counts and blood levels of the enzyme lactate dehydrogenase (LDH), their 12-week risk classification predicted their outcome, regardless of treatment. Overall 46% of low-risk patients survived 2 years, whereas only 2% of participants classified as high-risk were alive at this same time point.
The study suggests that “CTCs could well permit us to get ‘red light/green light’ answers for new drugs faster and more efficiently,” says Daniel Hayes, MD, of the University of Michigan Comprehensive Cancer Center in Ann Arbor. Hayes invented the CellSearch CTC capture technology but was not involved with the current study.
Future CTC-based approaches could also help identify which treatments are likely to work in individual patients. However, “that will require going beyond counting CTCs and providing more detailed molecular information, such as whether [patients] have acquired new mutations or have expression patterns that predict resistance or sensitivity to particular therapies,” says Daniel Haber, MD, PhD, a cancer geneticist at Massachusetts General Hospital, Boston, who did not take part in the research.
- ©2015 American Association for Cancer Research.
