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Expert Discusses Treatment Options in Advanced CRC

Angelica Welch
Published: Monday, Nov 13, 2017

Cathy Eng, MD
Cathy Eng, MD
There has been an ongoing conversation surrounding the use of TAS-102 as opposed to the multikinase inhibitor regorafenib (Stivarga) in patients with colorectal cancer (CRC) who have progressed on prior therapies.

Meeting, Eng, professor of gastrointestinal medical oncology at The University of Texas MD Anderson Cancer Center, discussed optimizing sequencing beyond disease progression in CRC. She also shed light on available treatments in CRC, encouraged physicians to dose adjust therapy for their patients, and highlighted studies further exploring immunotherapy in the field.

OncLive: Please provide an overview of your lecture on CRC.

Eng: I discussed what therapies are available to patients following first-line treatment, especially in the setting of progression of disease. I focused not only on the continuation of antiangiogenic agents in the second-line setting, but also the role of anti-EGFR therapy in the second- or third-line setting. Of course, there are the recent oral drugs that have been approved—regorafenib and TAS-102—in the refractory setting. I wanted to highlight some of the more recent trials that are more focused on rare subsets—specifically patients with a BRAF-mutated tumor—which is present in less than 10% of patients. It’s a very poor prognostic indicator. 

There are also some interesting data that are not necessarily new, but there is a new clinical trial focusing on the presence of HER2/neu amplification, and its association with anti-EGFR resistance. 

What factors do you consider when deciding between regorafenib and TAS-102 for a patient?

That is a great question. This is something that comes up all the time—whether you should use regorafenib or TAS-102. The reality is that they have different side effects; regorafenib may be associated with increased liver function studies. Therefore, if I have a patient with significant tumor burden in the liver, [regorafenib] may not be my first choice necessarily for them. It is also an antiangiogenic agent, so if you have a patient who is at risk, you have concerns about either blood pressure issues, a recent stroke, potential risk of bowel obstruction, or putting them at risk for perforation, then that would sway me away from regorafenib.

Whereas, TAS-102 results in increased myelosuppression. However, then you can kind of work around that either by adjusting the dose and the schedule or by providing filgrastim (Neupogen) or pegfilgrastim (Neulasta). However, I do want to highlight that they are both oral agents, so you have to follow patients and make sure that they are compliant with your recommendation. The myelosuppression from TAS-102 can result in a very dangerous situation. 

Are there any next steps we can take with regorafenib?

It was just approved recently for use in the second-line setting in the treatment of hepatocellular carcinoma. [Investigators] have obviously tried to look at it in combination with chemotherapy, but I am not exactly sure what the next steps are. It [involves] just trying to engage more physicians to utilize it.

I have to say: a lot of people have shied away from it because they started patients with the full dose [of regorafenib] and it resulted in significant hand-foot skin reactions—even though that is the dose in the FDA insert. In all fairness, I normally start my patients off at a lower dose of 120 mg daily.

Therefore, it is more so just figuring out the optimal dose—which might vary from patient to patient?

Correct. It is very much like in the old days when we utilized capecitabine; no one actually used the full dose. Everyone gave patients a lower dose and, as time goes by, you adjusted accordingly based on their hand-foot syndrome. 

What are some data from studies that have looked at the BRAF-mutant CRC population?

A recent study that was presented at the 2017 Gastrointestinal Cancers Symposium and 2017 ASCO Annual Meeting by my colleague Dr Scott Kopetz was SWOG 1406, which looked at a control arm of irinotecan and cetuximab (Erbitux) plus or minus vemurafenib (Zelboraf) with a primary endpoint of progression-free survival (PFS). The study was positive for PFS, and there was crossover allowed, so it was not positive for overall survival.

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