Marshall Discusses Role of Regorafenib in Second-Line mCRC Care

Gina Columbus @ginacolumbusonc
Published Online: Monday, Aug 29, 2016

John L. Marshall, MD

John L. Marshall, MD

Determining the next step of therapy when a patient with metastatic colorectal cancer (mCRC) progresses on first-line treatment centers on patient selection and preferences, explains John L. Marshall, MD.

“Of course, we have choices,” says Marshall. “We have regorafenib (Stivarga), we have TAS-102, we have recycling of chemotherapy, and we have clinical trials. Whereas, up until now, we were really pretty crisp about what we thought they should do next. [It was] ‘Here’s what we’re going to do first, here’s what we’re going to do second.’ Now it’s, ‘I’ve given you this buffet of choices.’”

Despite its commonly observed adverse event of hand-foot skin reaction, one agent in particular—regorafenib—has demonstrated a stable disease benefit since the FDA approved it in September 2012.

The approval was based on results of the randomized phase III CORRECT trial, which demonstrated a significant improvement in overall survival (OS) in patients who received treatment with regorafenib. The median OS was 6.4 months in the regorafenib arm and 5 months in the placebo arm (HR, 0.77; 95% CI, 0.64-0.94; P = .0102). Median PFS was 2 months for regorafenib and 1.7 months for placebo. (HR, 0.49; 95% CI, 0.42-0.58; P <.0001).

In an interview with OncLive, Marshall, chief of the Division of Hematology/Oncology at Medstar Georgetown University Hospital, and director of the Otto J. Ruesch Center for the Cure of Gastrointestinal Cancer, discusses second-line treatment options for patients with mCRC, along with who is most appropriate to receive regorafenib and how to manage doses and toxicities when using the multikinase inhibitor.

OncLive: How do you tell your patients they have progressed on second-line treatment? What are the implications for them?

Marshall: Most of the patients at this point are pretty savvy. They might even already know before I walk in the room that their scan is not good. With any patient, bad news is what oncologists do well. You each have your own way of telling a patient that things aren’t going in the right direction, so you tell them things are worse and you’re making a plan to move on to different therapy. The good news, of course, is that there are other therapies with proven OS benefit. You begin the discussion of “what next” and that’s when regorafenib comes up as the main next step.

The main benefit of regorafenib is stable disease, not response. How do you discuss those treatment objectives with patients?

The reality is, most of the time, frontline is where we see our response. Particularly in the RAS-mutated patient, there aren’t very many responses with second-line traditional chemotherapy. That is really true in third-line because studies show that regorafenib wasn’t really associated with any significant responders. It was significant stable disease.

In some patients, that’s important to dwell on. In others, it’s benefit. We talk about benefit, so the things I emphasize when presenting regorafenib is not exactly response versus not response; I explain that this is a medicine that controls your cancer. Forty percent of patients will have control of their cancer at their first scan at 8 weeks, and 20% or more will, in fact, have control of their cancer at 6 months. It is not so much emphasis around response; it’s about stabilization of their cancer in prolonging survival.

How do treatment objectives differ in third-line compared with those in first- and second-line?

It’s different now. Their objectives are different now; they still want to be cured—don’t get me wrong—but they also value quality of life more. When presenting regorafenib as an option here, you also don’t have to come and get infusions. You don’t have to carry a pump at home. You can take oral therapy and control your cancer. While we tend to dwell on side effects as oncologists, we need to really emphasize, in this case, the fact that it does stabilize their cancer that was growing previously.

Which patients are most eligible to receive regorafenib versus other therapies in this setting?

The best candidates for regorafenib, in my opinion, are patients who have had their initial lines of therapy and still have a very good performance status of 0 or 1 and, arguably, relatively small-volume disease. We don’t tend to think of this medicine in that space. We’ve tended to think of regorafenib as for a more “beat-up, heavier, no-other-option” kind of patient. The less “beat-up” patient clearly would get better benefit.


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