Michael J. Overman, MD

Michael J. Overman, MD, professor in the Department of Gastrointestinal Medical Oncology of the Division of Cancer Medicine and committee vice chair at The University of Texas MD Anderson Cancer Center, discusses potential applications for circulating tumor (ct)DNA in colorectal cancer. 

ctDNA is an exciting approach for which several potential and promising applications may exist. For example, this approach could potentially be utilized in the resistance space, specifically with regard to resistance mechanisms, says Overman. Examining the blood can provide information regarding the totality of the lesions or cancer spots; this offers a good assessment of various resistance mechanisms, notes Overman. 

Another potential application is with regard to minimal residual disease; this could be used to help detect cancer at a very low level and potentially engage upon it to guide treatment, says Overman. Another area of exploration is determining whether ctDNA could be used as an early marker for disease responsiveness to determine whether a treatment is working or not, adds Overman. Notably, ctDNA allows for the identification of quick changes because it’s cleared rapidly; it’s quantitative and it reflects many important aspects of cancer.

Responses are commonly evaluated with the use of tumor markers or scans; ctDNA could potentially offer a better surrogate for tumor response than a CT scan or other common tumor markers, says Overman. Research efforts are dedicated to determining whether ctDNA could become a standard part of assessment in terms of disease responsiveness, concludes Overman. 

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Michael J. Overman, MD, discusses potential applications for circulating tumor DNA in colorectal cancer. 

Dr. Overman on Potential Application of ctDNA in CRC

Michael J. Overman, MD, professor in the Department of Gastrointestinal Medical Oncology of the Division of Cancer Medicine and committee vice chair at The University of Texas MD Anderson Cancer Center, discusses ongoing research with immunotherapy in microsatellite stable (MSS) colorectal cancer (CRC).

The vast majority of patients with CRC are proficient in mismatch repair, says Overman. These patients have a high unmet need. Although immunotherapy has not shown a lot of success in patients with MSS tumors, an abundance of research is being done to decipher the complex microenvironment and bring this therapy to patients.

One of the more encouraging preliminary combinations in this space is regorafenib (Stivarga) and nivolumab (Opdivo), says Overman. Updated data, which were presented at the 2020 Gastrointestinal Cancers Symposium, are encouraging. However, the study results need to be validated before the combination is made available to patients, concludes Overman.

Dr. Overman on Ongoing Research With Immunotherapy in Microsatellite Stable CRC

Michael J. Overman, MD, professor in the Department of Gastrointestinal Medical Oncology of the Division of Cancer Medicine and committee vice chair at The University of Texas MD Anderson Cancer Center, discusses factors to consider when choosing between regorafenib (Stivarga) and TAS-102 (trifluridine/tipiracil; Lonsurf) in the third-line treatment of patients with colorectal cancer.

There are no data to make clear distinctions between regorafenib and TAS-102; therefore, treatment decisions are often based on the safety profiles of the agents. In the decision-making process, we take the characteristics of the patient and their concerns into consideration, says Overman. Generally, regorafenib tends to result in many adverse events that are more challenging for patients, including fatigue; TAS-102 tends to be less toxic in that regard. However, there is no right or wrong decision when choosing among these agents, according to Overman.

Dose-escalating regorafenib may make the agent more tolerable for patients, based on the results of the ReDOS trial, which showed relatively equivalent outcomes with standard dosing and a dose-escalated approach, says Overman. The main end point of the trial was the number of patients who reached the third cycle of therapy, but several others showed similar outcomes between arms. Safety data also looked better with the dose-escalated approach, concludes Overman.

Michael J. Overman, MD, discusses factors to consider when choosing between regorafenib and TAS-102 in the third-line treatment of patients with colorectal cancer.

Dr. Overman on Choosing Between Regorafenib and TAS-102 in CRC

Michael J. Overman, MD, professor in the Department of Gastrointestinal Medical Oncology of the Division of Cancer Medicine and committee vice chair at The University of Texas MD Anderson Cancer Center, discusses second-line therapy options for patients with colorectal cancer.

At time of progression, standard second-line chemotherapy options are available depending on what was used in the frontline setting, says Overman. For example, if an oxaliplatin-based therapy was used in the frontline, often irinotecan can be used in the second-line. If a triplet composed of fluoropyrimidine, irinotecan, and oxaliplatin was used in the frontline, these agents can be reintroduced at the time of progression, after maintenance therapy, according to Overman.

For molecular subtypes, such as tumors harboring 

 alterations, or in those with mismatch repair deficiency, targeted therapies can be used in the second-line setting, says Overman. It is important to test for these mutations early on in the treatment journey as that information can be used to inform future treatment decisions.

In the third- and fourth-line refractory setting, oral agents, such as regorafenib (Stivarga) or TAS-102 (trifluridine/tipiracil; Lonsurf), can be used, adds Overman. Clinical trials are always an option as well, concludes Overman.

Michael J. Overman, MD, discusses second-line therapy options for patients with colorectal cancer.

Author | Michael J. Overman, MD

Articles

Dr. Overman on Potential Application of ctDNA in CRC

Dr. Overman on Ongoing Research With Immunotherapy in Microsatellite Stable CRC

Dr. Overman on Choosing Between Regorafenib and TAS-102 in CRC

Dr. Overman on Second-Line Therapy Options for Colorectal Cancer