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Specific Oral Oncolytics

Peter L. Salgo, MD; Noa Biran, MD; Carl T. Henningson, MD; Arturo Loaiza-Bonilla, MD, MSEd, FACP; and Steven L. D’Amato, RPh, BSPharm, outline specific oral oncolytics, including ixazomib for multiple myeloma and regorafenib for gastrointestinal malignancies.
Published Online: Mar 14,2018

Peter L. Salgo, MD: I want to move on. We’ve been discussing money; we’ve been discussing society; we’ve been discussing all kinds of plans to improve adherence. I want to talk about real clinical medicine for a minute. Let’s take a look at some of these approved oral oncolytics. We’ve been talking about them in abstract. Let’s talk about specific ones. There’s one called ixazomib…?

Noa Biran, MD: Ixazomib.

Peter L. Salgo, MD: OK. That’s for your practice, right? That’s for multiple myeloma?

Noa Biran, MD: Yes. It’s an oral proteasome inhibitor that was approved in combination with lenalidomide and dexamethasone for patients with multiple myeloma. The precursor to that was bortezomib (Velcade), which was the subcutaneous injection. Now, a lot of people that were on an injection can be switched to an all-oral regimen. To have a 3-drug, all-oral regimen for patients with multiple myeloma was a novel, very exciting thing.

Carl T. Henningson, MD: It’s a big deal because Velcade is very labor intensive for patients. Patients would have to come in twice a week for 2 weeks on, 1 week off, endlessly, to get this drug. This is a regimen that patients can come in for—in some cases—once a month if they’re doing well.

Peter L. Salgo, MD: How long do you have to treat patients for?

Noa Biran, MD: Until progression. This is for the relapsed setting. So, once their disease relapses, they are on treatment forever—until the end of their life. So, this is an opportunity. With this treatment regimen, people can be on it for months to years.

Peter L. Salgo, MD: Tell me a bit about the drug. What’s the tolerance for this drug?

Noa Biran, MD: It’s given once a week. The side effects tend to be gastrointestinal related. You can have diarrhea, and you can have rare bowel perforation. It’s very rare, but you can have neuropathy. It’s less than with Velcade, but you can have neuropathy—and rashes. You can get some rare rashes around the eyes and around the whole body.

Peter L. Salgo, MD: Do patients like it? Do they prefer it?

Noa Biran, MD: Overall, yes, they do.

Peter L. Salgo, MD: And the cost?

Noa Biran, MD: I’m not sure, but it’s over $10,000 a month, for 3 pills a month.

Peter L. Salgo, MD: There’s giggling on the panel, but this is a real disease. What I mean by that is, there is real toxicity. It’s life limiting. This drug gives you life for not just a day or an hour but for months to years. So, this would pass all of the tests that we have discussed. This would pass the “this drug works” test. It adds a significant extension to your life expectancy. It’s taken at home. Patients like it. It passes the smell test on all of these things. Is there a downside to this at all, other than money?

Noa Biran, MD: No, it’s a good regimen.

Carl T. Henningson, MD: Again, the only downside would be for those practices that don’t have dispensing pharmacies, that aren’t making money on those drugs.

Peter L. Salgo, MD: OK, let’s go to another one. There’s regorafenib.

Arturo Loaiza-Bonilla, MD, MSEd, FACP: Right. Regorafenib is used mostly for gastrointestinal malignancies, particularly primary liver cancer and colorectal cancer. For liver cancer, we use it in the second-line setting. It is typically approved after another TKI [tyrosine kinase inhibitor] that we commonly use—sorafenib. So, regorafenib is used as second-line, rescue salvage therapy for those patients. It was one of the few drugs, after probably almost 10 phase III clinical trials, that showed some advantage after sorafenib. So, it is a new drug that we are using commonly in our patients.

Peter L. Salgo, MD: Is the drug curative? Palliative? What is it?

Arturo Loaiza-Bonilla, MD, MSEd, FACP: Unfortunately, it’s only for patients with stage IV disease that cannot be cured. But, we know that it can prolong survival. It is an oral agent that you can use, and it doesn’t exclude you from other potential therapies that you can be exposed to.

Peter L. Salgo, MD: When I look at colorectal cancer, the drug combination that comes to mind is FOLFOX, which is the old standard drug regimen.

Arturo Loaiza-Bonilla, MD, MSEd, FACP: We still use it. So, there is FOLFOX. Then, there is FOLFIRI plus or minus EGFR inhibitors, if you have the RAS wild-type and BRAF wild-type mutations, hopefully. But then, when you run out of options and you are not MSI–high—which is the new kid on the block for colorectal cancer—you have regorafenib, which is an oral drug. It’s 4 pills that you take once a day. It has some side effects, but we know we can prolong survival in patients heavily pretreated with colorectal cancer.

Peter L. Salgo, MD: What is the side effect profile of oral regorafenib compared with FOLFOX, for example? I’ve known patients on FOLFOX. It’s pretty nasty, despite the fact that the oncologist told them that it’s better than others.

Arturo Loaiza-Bonilla, MD, MSEd, FACP: Yes, it’s better than others. They’re completely different. FOLFOX gives you more neuropathy because of the oxaliplatin induced by the drugs—the platinum agents cause that neuropathy. Regorafenib is associated with more side effects from the gastrointestinal standpoint. It’s an oral drug. You take it by mouth. A number of patients have diarrhea. You also have something called hand-foot syndrome, or PPE (palmar-plantar erythrodysesthesia), which is very prominent in these patients. We are very much on top of those side effects. Those are the ones that we may consider the partial refill for, because we do dose escalation. Instead of taking 4 pills a day, you take 3. Then, you go up a week later, as the patient does well. What we know for sure is that most of the hand-foot syndromes that are really severe will appear within the first week or so, from treatment. So, you can actually fill the full dose once the patient is able to tolerate it.

Peter L. Salgo, MD: Again, these 2 drugs treat really significant cancers. These are oral agents. They are taken at home. They don’t have to go back. They don’t have to get the intravenous infusion. Is it my sense that the side effect profile, though different, is less severe than the intravenous side effect profile, or is that not true?

Arturo Loaiza-Bonilla, MD, MSEd, FACP: I think they’re different. If you are able to tolerate the dose, and you do the dose adjustment, you are able to have a good regimen that the patient will do well with and continue with. Neuropathy, for example, is pretty disabling, if you overcome the 10 cycles of oxaliplatin. So, we want to make sure that the patient is able to maintain a quality of life. To me, that’s first and foremost.

Peter L. Salgo, MD: What other tumors are out there for which oral oncolytics are available?

Steven L. D’Amato, RPh, BSPharm: All kinds. They are available for lung, breast, thyroid, and prostate. Then, you have the hematologic diseases. It’s all over the board now.

Peter L. Salgo, MD: This is coming. This is the new age.

Steven L. D’Amato, RPh, BSPharm: It’s here.

Carl T. Henningson, MD: It’s here.

Noa Biran, MD: It’s been here.

Peter L. Salgo, MD: It’s been here.

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