Tanios Bekaii-Saab, MD, professor of Medicine, Mayo Clinic, discusses microsatellite instability (MSI) in colorectal cancer.

The MSI group makes up about 4% of all patients with stage IV cancer. For those patients, studies suggest that using immunotherapies such as PD-1 inhibitors tend to induce significant responses that are both deep and durable, says Bekaii-Saab.

The question, though, is whether these PD-1 inhibitors would produce better outcomes than chemotherapy, or would add any benefit to chemotherapy in combination. If the research suggests that PD-1 inhibitors hold promising results in randomized trials in the first line, then it is likely that they will replace chemotherapy for MSI patients.

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Tanios Bekaii-Saab, MD, professor of Medicine, Mayo Clinic, discusses microsatellite instability in colorectal cancer.

Dr. Bekaii-Saab on Microsatellite Instability in Colorectal Cancer

Tanios Bekaii-Saab, MD, professor of Medicine, Mayo Clinic, discusses dosing strategies with regorafenib (Stivarga) in patients with colorectal cancer (CRC).

As an example, Bekaii-Saab says that out of 100 patients receiving regorafenib at the standard 160 mg regimen, 20 will remain on that dose. The majority will have to decrease treatment to 120 or possibly 80 mg, which is the lowest dose permitted. Some patients receive alternate doses or begin at a lower dose and escalate. However, alternating doses is not as effective, he adds, as there is a lack of anti-angiogenic pressure.

The ongoing ReDOS study is accruing 120 patients to compare the standard-dose strategy with an escalated-dose regimen as an approach to determine the right amount of treatment for patients with CRC.

Dr. Bekaii-Saab on Dosing Strategies With Regorafenib in CRC

Tanios Bekaii-Saab, MD, professor of Medicine, Mayo Clinic, discusses 2 new agents, regorafenib and TAS-102, for the treatment of patients with colorectal cancer.

Phase III studies have shown that both agents improved outcomes when compared with placebo in refractory settings, Bekaii-Saab explains.

Currently, there is only sequencing data for patients to receive regorafenib first followed by TAS-102; therefore, that is how the agents are used together. However, Bekaii-Saab emphasizes that there are certain instances where one therapy should be used versus the other.

View more from the 2016 School of Gastrointestinal Oncology

Tanios Bekaii-Saab, MD, professor of Medicine, Mayo Clinic, discusses about 2 agents, regorafenib and TAS-102, for the treatment of patients with treat colorectal cancer.

Dr. Bekaii-Saab on Active Agents for the Treatment of Colorectal Cancer

Tanios Bekaii-Saab, MD, associate professor, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, discusses the benefits patients receive with regorafenib for the treatment of colorectal cancer (CRC).

Though regorafenib and TAS-102 do not elicit partial or complete remissions, they do produce tumor shrinkage, Bekaii-Saab explains.

A study examined patients with lung metastases from the CORRECT trial, which investigated the efficacy of regorafenib versus placebo. With regorafenib, these tumors had a cavitation effect; cancer cells were killed without changing the size of the tumor. If patients have this lung cavitation, they will likely have tumor shrinkage and an improved progression-free survival, Bekaii-Saab says.

Tanios Bekaii-Saab, MD, associate professor, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, discusses the benefits patients receive with regorafenib for the treatment of colorectal cancer.


Dr. Bekaii-Saab on Benefits Associated With Regorafenib for CRC

Tanios Bekaii-Saab, MD, associate professor, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, discusses sequencing regorafenib and TAS-102 for the treatment of patients with colorectal cancer (CRC).

Phase III data from two separate clinical trials, RECOURSE and CORRECT, support the efficacy of oral targeted therapy regorafenib and cytotoxic agent TAS-102, Bekaii-Saab explains. However, neither study specifically examined TAS-102 prior to treatment with regorafenib.

In clinical practice, patients first receive regorafenib and, upon progression, are administered TAS-102. However, if a patient has liver function abnormalities or hand-foot syndrome, TAS-102 may be moved ahead of regorafenib in the therapy sequence. Patients who experience significant bone marrow toxicities are less likely candidates to receive TAS-102 upfront, Bekaii-Saab adds.

View more from the 2016 GI Cancer Symposium

Tanios Bekaii-Saab, MD, associate professor, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, discusses sequencing regorafenib and TAS-102 for the treatment of patients with colorectal cancer. 


Dr. Bekaii-Saab on Sequencing Regorafenib and TAS-102 in CRC

Tanios Bekaii-Saab, MD, Section Chief, Gastrointestinal Oncology, associate professor, Internal Medicine, Pharmacology, The Ohio State University, discusses the results of a phase II study of the oncolytic virus reolysin in the first-line treatment metastatic adenocarcinoma of the pancreas.

The virus did not improve outcomes in the overall population of 73 patients in this study. Some patients may have benefited, Saab says, and researchers are still looking at blood and tissue samples for a potential biomarker. Interestingly, of the patients that crossed over, one patient responded and one had stable disease — this can most likely be attributed to the virus.

Tanios Bekaii-Saab, MD, discusses the results of a phase II study of the oncolytic virus reolysin in the first-line treatment metastatic adenocarcinoma of the pancreas.

Dr. Saab on a Phase II Study of the Oncolytic Virus Reolysin for Pancreatic Cancer

Tanios Bekaii-Saab, MD, Section Chief, Gastrointestinal Oncology, associate professor, Internal Medicine, Pharmacology, The Ohio State University, discusses an analysis of two targeted drugs for the treatment of patients with colorectal cancer (CRC).

This seven-year national trial compared bevacizumab and cetuximab in combination with FOLFOX and FOLFIRI for CRC. While previous studies have shown that the combination of bevacizumab/chemotherapy and the combination of cetuximab/chemotherapy both improve outcomes, the two agents have never been compared head to head. This study is the first study to compare bevacizumab and cetuximab head to head.

Results from this large trial suggest no difference in overall survival or progression-free survival. One complexity of this trial was that the chemotherapy was one of choice, Bekaii-Saab says. Researchers on this trial also hypothesize that FOLFIRI is a better backbone.

Tanios Bekaii-Saab, MD, discusses an analysis of two targeted drugs for the treatment of patients with colorectal cancer (CRC).

Tanios Bekaii-Saab, MD

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