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Practical Advice for Using Regorafenib

Insights From:John L. Marshall, MD, Georgetown University Hospital;Mohamed E. Salem, MD, Georgetown University Hospital;Monica Chacha, RN, BSN, OCN, Georgetown University Hospital
Published: Monday, Aug 29, 2016


Transcript:

John L. Marshall, MD:
So, in the last year, about 40 new cancer medicines were approved. And I, as a GI oncologist, have the good fortune of only having to know about a couple of them. But you out there have to deal with every one of these. So, if you’re like most, these new medicines are new to you. And you can look them up online, you can figure out how to deal with them by asking friends and neighbors. But, really, until you’ve tried it, until you’ve used it, it doesn’t really click. Let me give you some ‘inside baseball,’ if you will, on the management of Stivarga, or regorafenib, that may help you out there in the community.

First, don’t get all hung up on the fact that there are no responses. There weren’t many responses in the second-line therapy. It’s really a drug that stabilizes disease in about half of the patients; 40% to 50% will stabilize, and another 20% will stabilize as long as 6 months. This is valuable time for our patients, so don’t leave this survival advantage on the table. The reason you might balk about this has been the toxicity or the lure of the toxicity. And the standard dose of four tablets daily for 3 weeks in a row, 1 week off, is very difficult to give to most patients.

Most of us who are using this drug regularly have different strategies for different patients. Most start at a reduced dose, maybe 120 mg. Some will even start at 80 mg and then dose-escalate depending on how they tolerate it. But if you do start at 160 mg, watch them really closely, because you’re likely to have to come down on dose. Watch their hands, watch their livers, watch their GI tract, and watch their fatigue. These are the key things to keep an eye out for early on. Make the dose adjustments, get them through that first couple of months of treatment, assess whether they’re going to be the 1 in 5 that’s going to respond and benefit for as much as 6 months, and get those patients through that treatment. I think you’ll have a better experience with this refractory setting in these new medicines.

Mohamed E. Salem, MD: Regorafenib is a tyrosine kinase inhibitor. It’s actually a multi-targeted agent and hits several targets like BRAF, RET, and several others. In reality, we’re not sure exactly how it does work, but this is the hypothesis behind it. The drug was approved by the FDA for patients with refractory colon cancer who received 5-FU, a fluoropyrimidine-based therapy; oxaliplatin; irinotecan; or bevacizumab. And if they are RAS wild-type, they also should have had anti-EGFR.

John L. Marshall, MD: This is an important moment for patients. We’ve been taking care of them for a couple of years. They know the parking lot attendant’s name. They know how to do everything. They’re cancer veterans, if you will. A lot of times people focus on the response rate of these two medicines, that there isn’t an actual response rate. But we have to remember that it controls cancer in about half the patients; about 20% will have 6-month stabilization. Those are very valuable chunks of time for patients in this refractory setting, so we don’t want to minimize or de-value that control. But what are some of the other important things at this point for our patients?

Monica Chacha, RN: I think conversations we’re having at this time are (1) quality of life: how do they want their life to look right now while they’re on these medications? And then (2) we’re having a lot of discussions about goals of care, like what is the plan going forward? What is their goal?

John L. Marshall, MD: And we often haven’t had that discussion since maybe day 1, where the focus is aggressive and on management. But now that patient is a better consumer. Quality of life is important. Mohamed?

Mohamed E. Salem, MD: I agree with both aspects. I also agree with the quality of life. Because, at this time, you really want to also highlight that maybe they should take vacation time, they should go with their family, go to their grandkid’s graduation. And I don’t say, “Okay, you have to come on this cycle and that date.” You allow them to do what they like to do.

John L. Marshall, MD: So, a great advantage of these oral therapies is they’re free—they don’t have to come every 2 weeks and get IVs. They can do these kinds of things, and it makes for a perfect time for us as healthcare providers to readdress those really important goals of care for our patients.

Mohamed E. Salem, MD: The study that got the drug to be approved is the CORRECT study, which was published by Dr. Grothey in Lancet Oncology in 2015. The study included about 760 patients. The primary endpoint was overall survival. The secondary endpoints were progression-free survival, response rate, toxicity, and safety. The study was positive: it met the endpoint of overall survival in the regorafenib arm of about 6 months versus 5 months in the placebo arm, with a benefit of about 1.4 months’ improvement in survival. The secondary endpoint also was positive. The hazard ratio for the survival benefit was about 0.77.

Transcript Edited for Clarity
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Transcript:

John L. Marshall, MD:
So, in the last year, about 40 new cancer medicines were approved. And I, as a GI oncologist, have the good fortune of only having to know about a couple of them. But you out there have to deal with every one of these. So, if you’re like most, these new medicines are new to you. And you can look them up online, you can figure out how to deal with them by asking friends and neighbors. But, really, until you’ve tried it, until you’ve used it, it doesn’t really click. Let me give you some ‘inside baseball,’ if you will, on the management of Stivarga, or regorafenib, that may help you out there in the community.

First, don’t get all hung up on the fact that there are no responses. There weren’t many responses in the second-line therapy. It’s really a drug that stabilizes disease in about half of the patients; 40% to 50% will stabilize, and another 20% will stabilize as long as 6 months. This is valuable time for our patients, so don’t leave this survival advantage on the table. The reason you might balk about this has been the toxicity or the lure of the toxicity. And the standard dose of four tablets daily for 3 weeks in a row, 1 week off, is very difficult to give to most patients.

Most of us who are using this drug regularly have different strategies for different patients. Most start at a reduced dose, maybe 120 mg. Some will even start at 80 mg and then dose-escalate depending on how they tolerate it. But if you do start at 160 mg, watch them really closely, because you’re likely to have to come down on dose. Watch their hands, watch their livers, watch their GI tract, and watch their fatigue. These are the key things to keep an eye out for early on. Make the dose adjustments, get them through that first couple of months of treatment, assess whether they’re going to be the 1 in 5 that’s going to respond and benefit for as much as 6 months, and get those patients through that treatment. I think you’ll have a better experience with this refractory setting in these new medicines.

Mohamed E. Salem, MD: Regorafenib is a tyrosine kinase inhibitor. It’s actually a multi-targeted agent and hits several targets like BRAF, RET, and several others. In reality, we’re not sure exactly how it does work, but this is the hypothesis behind it. The drug was approved by the FDA for patients with refractory colon cancer who received 5-FU, a fluoropyrimidine-based therapy; oxaliplatin; irinotecan; or bevacizumab. And if they are RAS wild-type, they also should have had anti-EGFR.

John L. Marshall, MD: This is an important moment for patients. We’ve been taking care of them for a couple of years. They know the parking lot attendant’s name. They know how to do everything. They’re cancer veterans, if you will. A lot of times people focus on the response rate of these two medicines, that there isn’t an actual response rate. But we have to remember that it controls cancer in about half the patients; about 20% will have 6-month stabilization. Those are very valuable chunks of time for patients in this refractory setting, so we don’t want to minimize or de-value that control. But what are some of the other important things at this point for our patients?

Monica Chacha, RN: I think conversations we’re having at this time are (1) quality of life: how do they want their life to look right now while they’re on these medications? And then (2) we’re having a lot of discussions about goals of care, like what is the plan going forward? What is their goal?

John L. Marshall, MD: And we often haven’t had that discussion since maybe day 1, where the focus is aggressive and on management. But now that patient is a better consumer. Quality of life is important. Mohamed?

Mohamed E. Salem, MD: I agree with both aspects. I also agree with the quality of life. Because, at this time, you really want to also highlight that maybe they should take vacation time, they should go with their family, go to their grandkid’s graduation. And I don’t say, “Okay, you have to come on this cycle and that date.” You allow them to do what they like to do.

John L. Marshall, MD: So, a great advantage of these oral therapies is they’re free—they don’t have to come every 2 weeks and get IVs. They can do these kinds of things, and it makes for a perfect time for us as healthcare providers to readdress those really important goals of care for our patients.

Mohamed E. Salem, MD: The study that got the drug to be approved is the CORRECT study, which was published by Dr. Grothey in Lancet Oncology in 2015. The study included about 760 patients. The primary endpoint was overall survival. The secondary endpoints were progression-free survival, response rate, toxicity, and safety. The study was positive: it met the endpoint of overall survival in the regorafenib arm of about 6 months versus 5 months in the placebo arm, with a benefit of about 1.4 months’ improvement in survival. The secondary endpoint also was positive. The hazard ratio for the survival benefit was about 0.77.

Transcript Edited for Clarity
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