Van K. Morris, MD, an associate professor in the Department of Gastrointestinal (GI) Medical Oncology of the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, discusses the evaluation of circulating tumor (ctDNA) as a predictive biomarker for the use of adjuvant chemotherapy in patients with low-risk, stage II colon cancer.

The ongoing phase 2/3 NRG-GI005 (COBRA) study (NCT04068103) is evaluating the use of ctDNA in this patient population as a predictive biomarker to identify patients who may or may not benefit from chemotherapy following surgery. After undergoing surgery, patients in arm A will undergo active surveillance, and blood drawn at baseline will be stored and later tested for ctDNA. Those in arm B will have blood drawn following surgery, and it will be tested at baseline to determine ctDNA status. Those who are ctDNA negative will undergo surveillance, and those who are ctDNA positive will receive adjuvant chemotherapy.

The co-primary end points of the trial are the clearance of ctDNA to undetectable levels for those who have ctDNA detected at baseline, as well as recurrence-free survival (RFS) for patients who are ctDNA positive at baseline. Secondary outcomes included RFS in the overall population, overall survival, and time to recurrence.

ctDNA is a powerful and useful tool across the oncology landscape, and detectable ctDNA after the completion of definitive therapies or surgery is highly prognostic for the chance that a patient’s cancer could return, Morris says. Conversely, patient with undetectable ctDNA, are less likely to recur, Morris adds.

However, investigators are still aiming to collect strong, prospective evidence on the use of ctDNA to guide clinicians and patients regarding treatment decisions that could help improve outcomes. Along with investigating ctDNA clearance rates in patients with ctDNA positivity, investigators hope to better understand how this correlates with survival outcomes, Morris concludes.

Videos

Van K. Morris, MD, discusses the evaluation of circulating tumor as a predictive biomarker for the use of adjuvant chemotherapy in patients with low-risk, stage II colon cancer.

Dr. Morris on the Investigation of the Role of ctDNA in Stage II CRC 

Van K. Morris, MD, assistant professor in the Department of Gastrointestinal Medical Oncology of the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, discusses the design of the prospective phase 2/3 NRG-GI005 (COBRA) trial evaluating circulating tumor DNA (ctDNA) as a predictive biomarker for adjuvant chemotherapy in patients with colon cancer.

The trial is enrolling patients with resected stage IIa colon cancer who have been deemed suitable for active surveillance per standard of care clinical practices, says Morris.

These patients do not often receive adjuvant chemotherapy as their prognosis is favorable and additional chemotherapy is not considered optimal, Morris adds.

Patients enrolled in the study are randomized to receive active surveillance or assay-directed therapy based on the presence or absence of ctDNA, Morris explains.

Patients with detectable ctDNA will receive 12 cycles of modified leucovorin/5-fluorouracil/oxaliplatin (mFOLFOX6) or 8 cycles of capecitabine and oxaliplatin (CAPOX) per physician’s choice.

Van K. Morris, MD, discusses the design of the prospective phase 2/3 NRG-GI005 (COBRA) trial evaluating circulating tumor DNA as a predictive biomarker for adjuvant chemotherapy in patients with colon cancer.  



Dr. Morris on the Design of the COBRA Trial in Stage II Colon Cancer 

Van K. Morris, MD, assistant professor in the Department of Gastrointestinal Medical Oncology of the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, discusses the role of circulating tumor DNA (ctDNA) in resected colon cancer.

Regardless of stage, patients with colon cancer who have detectable ctDNA following surgery are at a higher risk of recurrence compared with those who have undetectable ctDNA after resection, explains Morris. 

The presence of ctDNA in colon cancer serves as a surrogate for the presence of microscopic minimal residual disease, Morris says. Moreover, ctDNA has been shown to be a valid prognostic biomarker to stratify patients by their risk of recurrence. 

However, utilizing ctDNA as a predictive biomarker to determine whether a patient is likely to respond to chemotherapy requires further research, concludes Morris.

Van K. Morris, MD, discusses the role of circulating tumor DNA in resected colon cancer.  



Dr. Morris on the Role of Circulating Tumor DNA in Resected Colon Cancer 

Van K. Morris, MD, assistant professor, Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the role of immunotherapy in metastatic colorectal cancer (CRC).

Immunotherapy has been an exciting addition to the armamentarium of metastatic CRC in the past few years, explains Morris.

However, only approximately 3% to 5% of all patients with metastatic CRC have microsatellite instability—high disease that is amenable to immunotherapy, says Morris. These patients can have favorable long-term outcomes with immunotherapy.

Translating these outcomes to patients with metastatic CRC who have microsatellite stable disease is an area of active research, concludes Morris.

Van K. Morris, MD, discusses the role of immunotherapy in metastatic colorectal cancer.



Dr. Morris on the Role of Immunotherapy in Metastatic CRC

Van K. Morris, MD, assistant professor, Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the role of immunotherapy in metastatic colorectal cancer (CRC).

Immunotherapy has been an exciting addition to the armamentarium of metastatic CRC in the past few years, explains Morris.

However, only approximately 3% to 5% of all patients with metastatic CRC have microsatellite instability–high disease that is amenable to immunotherapy, says Morris. These patients can have favorable long-term outcomes with immunotherapy.

Translating these outcomes to patients with metastatic CRC who have microsatellite stable disease is an area of active research, concludes Morris.

Van K. Morris, MD, discusses the role of immunotherapy in metastatic colorectal cancer.

Van K. Morris, MD, assistant professor, Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the recent progress made in the treatment of patients with 

-mutated metastatic colorectal cancer (mCRC).

The use of molecular profiling in patients with mCRC has provided insight on how to best treat patients whose tumors harbor certain aberrations, says Morris. For example, patients with

-mutated mCRC account for 10% of all patients with mCRC and they tend to have bad prognoses. The median survival for these patients is 12 months compared with 2.5 years in those without the alteration, adds Morris.

Recently, combinations of therapies that target the MAPK pathway have resulted in improved survival outcomes in those with 

-mutated disease; this is the first time that targeted therapies have shown to be effective for this patient population, concludes Morris.

Van K. Morris, MD, discusses the recent progress made in the treatment of patients with BRAF-mutated metastatic colorectal cancer.

Dr. Morris on Treatment Advances Made in BRAF-Mutated mCRC

Van K. Morris, MD, assistant professor, Department of Gastrointestinal Oncology, The University of Texas MD Anderson Cancer Center, discusses his research around treatment for patients with unresectable colorectal cancer (CRC), in an interview during the 2020 Gastrointestinal Cancers Symposium.

A pooled analysis evaluated the outcomes of patients with surgically unresectable CRC who were treated in the phase II TRIBE and phase III TRIBE-2 studies with chemotherapy plus bevacizumab (Avastin). The investigators set out to determine whether or not the oligometastatic status of patients was indicative of response, and whether it could aid in deciding which patients should be given doublet or triplet cytotoxic chemotherapy, says Morris.

Results showed that patients with oligometastatic disease had better survival outcomes than those with nonoligometastatic disease. Interestingly, when investigators looked at patients with oligometastatic disease versus those with nonoligometastatic disease and analyzed how they fared when they received 2 cytotoxic agents versus 3 cytotoxic agents, no difference in survival outcomes was observed between the 2 groups, adds Morris. Based on these findings, oligometastatic status is not a good determinant of whether to give doublet or triplet cytotoxic chemotherapy to patients with unresectable CRC.

The investigators also looked at the roles of locoregional therapy in patients with unresectable metastatic CRC. Data showed that a significant proportion of the patients who either had oligometastatic disease or nonoligometastatic disease were able to undergo the treatment. However, those with oligometastatic disease were more likely to be able to withstand more local regional therapies, concludes Morris.

 View more from 2020 Gastrointestinal Cancers Symposium

Van Morris, MD, discusses research around treatment for patients with unresectable colorectal cancer.

Dr. Morris on Optimizing CRC Treatment Based on Oligometastatic Status

Van K. Morris, MD, assistant professor of GI Oncology, The University of Texas MD Anderson Cancer Center, discusses a study examining nivolumab (Opdivo) as a potential treatment for patients with anal cancer.

In a study looking at pretreated patients with metastatic anal cancer, researchers at The University of Texas MD Anderson Cancer Center examined the efficacy of single-agent nivolumab. Responses were seen in 5 of 18 patients—a 28% overall response rate. Of the 18 patients, 9 provided paired biopsies.

Patients who responded to nivolumab were found to have higher levels of CD8-positive and granzyme B cells at baseline. Although this is a small study, the increased levels of activated T cells suggests a response to nivolumab. Additionally, patients who responded were found to have higher levels of PD-1/PD-L1. 

Van K. Morris, MD, assistant professor of GI Oncology, The University of Texas MD Anderson Cancer Center, discusses a study examining nivolumab (Opdivo) as a potential treatment for patients with anal cancer.


Van K. Morris, MD

Articles

Dr. Morris on the Investigation of the Role of ctDNA in Stage II CRC

Dr. Morris on the Design of the COBRA Trial in Stage II Colon Cancer

Dr. Morris on the Role of Circulating Tumor DNA in Resected Colon Cancer

Dr. Morris on the Role of Immunotherapy in Metastatic CRC

Dr. Morris on the Role of Immunotherapy in Metastatic CRC

Dr. Morris on Treatment Advances Made in BRAF-Mutated mCRC

Dr. Morris on Optimizing CRC Treatment Based on Oligometastatic Status

Dr. Van Morris on Nivolumab as a Potential Treatment for Patients With Anal Cancer