Dosing and Toxicity: Management of Lenvatinib for Patients With Advanced HCC

FINN: This patient started on lenvatinib 12 mg daily. Lenvatinib is dosed by weight. Patients who weigh more than or equal to 60 kg get 12 mg.¹ Patients weighing less than 60 kg get 8 mg. These doses are lower than [those] used in kidney cancer and thyroid cancer.

This patient has weight loss and is dose reduced to 8 mg and is referred to...nutrition therapy. Weight loss and loss of appetite are probably 2 of the most common adverse events [AEs] we see with the drug [Figure 1²]. At 16 weeks, [she does] have a PR. Keep in mind, while most of the tyrosine kinase inhibitors [TKIs] have singledigit objective response rates [ORR], lenvatinib is the one TKI that had double-digit RECIST ORR.²

After 8 months of being on treatment, lenvatinib is discontinued for disease progression.

FINN: What are your thoughts on the toxicity profiles of lenvatinib and sorafenib [Nexavar]. Does this affect how you use either sorafenib or lenvatinib and [manage] these toxicity profiles?

MUSHTAQ: I used sorafenib a couple years ago. It’s a pretty hard drug, and it’s not easy to use compared with lenvatinib, especially if you’re using a dose of lenvatinib less than 16 mg, like the 12-mg [dose for HCC], which is pretty well tolerated. Mainly the issues [with sorafenib] are diarrhea, which you can manage, and rash,³ which I have also seen. Looking at efficacy and toxicity, I’ll probably go with lenvatinib, although the overall survival benefit was not statistically significant.²

FINN: The GI [gastrointestinal] toxicity is not too different between the 2 drugs. However, there’s more hand-foot syndrome with sorafenib and it is higher grade, [and] there is more hypertension with lenvatinib vs sorafenib. Do you manage these proactively? What is your approach to keeping patients on the drug and managing these AEs? Or do you see some different AEs that you have challenges managing?

CHEN: I see more hypertension with lenvatinib, and oftentimes, we do need to put people on more hypertensives for that. I usually have my patients record their blood pressure. I do see more of an appetite loss or weight loss [with lenvatinib], but I think overall those are able to be managed well. So I tend to use lenvatinib a lot more now than sorafenib.

FINN: How do you manage the weight loss and anorexia? That’s probably the hardest thing for me because there’s no quick fix.

CHEN: [There are] no good ways. Make sure to have them see a nutritionist, make sure they are taking supplements [such as] Ensure and Boost, and use dose modifications.

ZHOU: I have patients [for whom] the problem is the mucositis.

FINN: Yes, some patients do tend to get mucositis. That can be a challenge. There are mucositis [treatments], viscous lidocaine. Sometimes you do need to use a dose reduction. Not the most common AE, but it certainly can be seen.

FARJAMI: I have a couple of cases that have very poorly controlled blood pressure, despite all the efforts and consultants. We ended up switching from lenvatinib to sorafenib. I would say it’s a challenge in some patients, specifically if they have a history of ischemic heart disease or any prior history of a stroke.

FINN: While they are both VEGF receptor inhibitors, lenvatinib is clearly a much more potent compound, and [that] probably explains this difference.

RASILA: I’ve used lenvatinib. The main AE is hypertension. For most patients, it’s manageable. I did have one patient who ended up in the emergency department with a hypertensive emergence, and we did end up discontinuing the lenvatinib. But most of the time, it’s manageable.

FINN: Do you see your patients on lenvatinib on a regular basis? Even though these drugs are oral, I think the patients still need to be seen [regularly] because there are toxicities.

RASILA: Yes, usually anytime I’m starting a new TKI, I will see them 7 to 10 days after. I usually prefer an office visit so I can see if there is any rash, hand-foot-mouth sores, and what their blood pressure is. If they’re doing OK, I’ll [see them] every 2 weeks [initially, and] if they’re fine, then they’ll go to monthly. We are doing more [telemedicine] visits. [Although] for some problem patients, we will still have them do home blood pressure readings. But if there’s something I can’t see on the video, we’ll have them come into the office.

FINN: The one thing we did not touch on specifically is hypothyroidism. TSH [thyrotropin] should be checked intermittently on these patients. It is not uncommon for patients to develop hypothyroidism with lenvatinib.

FINN: Typically in liver cancer, patients receive 4-mg lenvatinib tablets, and that’s easy to adjust from 12 mg to 8 mg to 4 mg [Figure 2¹ ]. If they start at 8 mg, 8 mg to 4 mg, to 4 mg every other day. Sorafenib is at 200 mg, [which] we’ve been using for a long time with 2 tablets twice a day, [reduced to] 2 tablets once a day, [then to] 2 tablets every other day. There are no specific contraindications on the label for lenvatinib [Warnings for Prescribing Lenvatinib¹ ]. Certainly, hypersensitivity could be included there. The boxed warnings are reflective of a class effect, [including] a few more AEs such as proteinuria because it’s a more potent VEGF inhibitor.