Georges Azzi, MD, co-director, Department of Hematology/Oncology, Prostate Cancer, Holy Cross Health, discusses the utilization of the Signatera circulating tumor DNA (ctDNA) assay in the ongoing phase 2/3 CIRCULATE-US (NRG-GI008) trial in colorectal cancer (CRC).

In the CIRCULATE-US trial, if ctDNA is detected, patients are randomization between standard of care chemotherapy given over the course of 6 months vs FOLFOXIRI, Azzi explains. However, if ctDNA is not detected by the assay, patients are randomization between standard chemotherapy vs surveillance with serial ctDNA testing, Azzi adds.

Moreover, if the ctDNA is not detected, patients on survellience will continue without chemotherapy; however, if serial ctDNA testing detects ctDNA during follow-up, patients will be randomized to the chemotherapy regimens, Azzi continues. Ultimately, the first arm of the study will include patients who receive up-front chemotherapy based on the presence of ctDNA, whereas the second arm will include those patients who receive chemotherapy after based on the initial absence of ctDNA, Azzi concludes.

Videos

Georges Azzi, MD, co-director, Department of Hematology/Oncology, Prostate Cancer, Holy Cross Health, discusses the utilization of the Signatera circulating tumor DNA assay in the ongoing phase 2/3 CIRCULATE-US trial in colorectal cancer. 

Dr. Azzi on the Utilization of the Signatera ctDNA Assay in the CIRCULATE-US Trial in CRC 

Georges Azzi, MD, co-director, Department of Hematology/Oncology, Prostate Cancer, Holy Cross Health, discusses the unmet needs the Signatera circulating tumor DNA (ctDNA) assay could fulfill in colorectal cancer (CRC).

Currently, the field of CRC does not have an available assay to inform which patients are at a high risk of recurrence, Azzi says. Although pathological criteria are available, certain elements that can be used to inform treatment selection, such as the presence of positive lymph nodes, do not predict disease-free survival as well as tumor-informed ctDNA assays, Azzi explains. 

As such, the Signatera assay is the most useful method of determining risk of recurrence in patients with CRC. The test is being utilized in the ongoing phase 2/3 CIRCULATE-US (NRG-GI008) trial, Azzi adds. Moreover, an assay such as the Signatera one could also provide insight into treatment escalation and de-escalation strategies, Azzi concludes.

Georges Azzi, MD, discusses the unmet needs the Signatera circulating tumor DNA assay could fulfill in colorectal cancer. 



Dr. Azzi on the Unmet Needs the Signatera ctDNA Assay Could Fulfill in CRC 

Georges Azzi, MD, co-director, Department of Hematology/Oncology, Prostate Cancer, Holy Cross Health, discusses the rationale for the phase 3 CIRCULATE study (NCT04089631) in colorectal cancer (CRC).

Adjuvant chemotherapy has not been shown to have curative potential for all patients with CRC, Azzi says. As such, the goal of the CIRCULATE trial is to attempt to improve upon the current adjuvant chemotherapy regimens that are given to patients after surgery, Azzi explains. The best way to do this is to be able to escalate adjuvant therapy in high-risk patients, Azzi adds.

Moreover, tumor-informed circulating DNA is a valuable tool used to evaluate risk based on minimal residual disease (MRD) status, Azzi continues. If a patient tests positively for MRD 4 weeks after their surgery, they have are at a much higher risk of recurrence, Azzi adds.

In CIRCULATE, ctDNA will be the guiding factor for randomization, wherein patients with MRD-negative disease will de-escalate adjuvant chemotherapy and patients with MRD-positive disease will escalate therapy, Azzi concludes.

Georges Azzi, MD, discusses the rationale for the phase 3 CIRCULATE study in colorectal cancer. 


Dr. Azzi on the Rationale for the CIRCULATE Study in CRC 

Georges Azzi, MD, co-director, Department of Hematology/Oncology, Prostate Cancer, Holy Cross Health, discusses the utility of the Signatera circulating tumor DNA (ctDNA) assay as a preferred test in colorectal cancer (CRC). 

The CIRCULATE-Japan study is the largest prospective tumor-informed ctDNA study conducted to date. The trial analyzed patients with stage II to IV resectable CRC with the goal of refining adjuvant therapy. Moreover, results from the study underscored the utility of the Signatera assay, which is associated with a 95% presurgical detection rate, Azzi says. At 4 weeks, the results demonstrated that patients with stage I to III disease who were ctDNA positive postoperatively had a hazard ratio of 24.4, Azzi says.  

Moreover, based on the ctDNA assay having validated data available and demonstrating utility for the detection of metastatic disease, the Signatera assay is being widely utilized by a variety of groups, such as Medicare, in the advanced cancer setting to monitor the molecular tumor burden, Azzi explains. 

If patients are responding to therapy, they will have a decrease in theirmolecular tumor burden. Moreover, the Signatera assay can identify that decrease at 6 weeks after treatment initiation vs many months with conventional imaging, Azzi adds. The assay presents the ability to detect responses or progression, as well as the ability to differentiate between pseudo-progressionand progression, which is important when utilizing immunotherapy, Azzi concludes.

Georges Azzi, MD, discusses the utility of the Signatera circulating tumor DNA assay as a preferred test in colorectal cancer (CRC).  


Georges Azzi, MD

Articles

Dr. Azzi on the Utilization of the Signatera ctDNA Assay in the CIRCULATE-US Trial in CRC

Dr. Azzi on the Unmet Needs the Signatera ctDNA Assay Could Fulfill in CRC

Dr. Azzi on the Rationale for the CIRCULATE Study in CRC

Dr. Azzi on the Utility of Signatera as a Preferred ctDNA Assay in CRC