Proactive Side Effect Management With Regorafenib


Andrea Cercek, MD: What we have seen with regorafenib, in the initial study (the CORRECT study), is that a number of patients have hand-foot toxicity. I think that remains to be the major toxicity associated with the drug. There’s also diarrhea and hypertension. Those are the main toxicities that are associated with the drug. When the drug was accepted, and it started to be used in clinical practice, the hand-foot toxicity was really the major limiting factor to patients being able to tolerate it. Then, it eventually also affected clinicians prescribing it as a first-line option in the third-line refractory setting.

Zev A. Wainberg, MD: When patients are due to start on a drug like regorafenib, which, admittedly, is primarily approved and used in later lines of therapy, an approach to symptom management is critical. We have to make sure that patients are not just able to handle the pill, but that it’s helping some of the side effects that are induced by the cancer, itself, at that stage.

When we talk to patients about how to cope with this drug, we say, “We’re going to start you at a lower dose and escalate.” We learned quite a bit about this at ASCO’s 2018 Gastrointestinal Cancers Symposium. But many of us, for a long time, have not felt that dosing regorafenib at 160 mg is a tolerable strategy for many patients.

Tanios Bekaii-Saab, MD, FACP: The 160-mg dose had been our standard, all the way through. Certainly, for many patients, it’s a tough dose. We find ourselves having to reduce the dose to 120 mg or, on occasion, even to 80 mg for the majority of patients. However, about 20% of patients do tolerate the 160-mg dose very well and continue with it. I just saw one of my patients last month. This patient has been on regorafenib, 160 mg, for 9 months. The patient is doing very well, with very minimal toxicities. So, we have those patients, and we know, from the CORRECT trial, that this trend occurs in about 20% of patients.

ReDOS redefines the way that we optimize the dose. It really takes advantage of the critical importance of that first cycle. As such, my strategy has shifted from giving 160 mg daily for 3 weeks on and 1 week off to a dose-escalation strategy with a goal to reach 160 mg. So, 80 mg, 120 mg, 160 mg on a weekly basis and, a week off.

In our study of ReDOS, we had second randomization, which essentially included patients being randomized to what we call a preemptive approach versus a reactive approach with steroid cream (clobetasol) applied to hands and feet. So far, we haven’t seen any signals. We’re still looking deep into the data to understand whether we truly could preempt hand-foot syndrome. We’ll present some of this data in later Congresses.

The most important message remains the same. The first 4 weeks of exposure to regorafenib and TAS-102 [trifluridine/tipiracil] are critical. It’s very important to follow the patients closely. With regorafenib, we see the patients every week for the first cycle and then, after that, every 2 weeks for the second cycle. Then, after that cycle, when going into the third cycle, patients will be seen on a monthly basis. But it is critical to see the patients on a weekly basis. And now I believe that this strategy with 80 mg, 120 mg, and 160 mg will naturally happen. You will see the patient on a weekly basis. I would still see them, of course, before I start cycle 2. So, the first cycle is going to be involved with the patient. You should see the patient on a weekly basis.

Transcript Edited for Clarity

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