Patient Factors in Choosing Optimal Agents in HCC Therapy

Catherine Frenette, MD:Lenvatinib [Lenvima] dosing is either 2 or 3 pills a day. We want to remember to tell the patients to take them all at once; it doesn’t matter whether that is in the morning or night. I let patients choose. It can be with or without food, which makes dosing a bit easier for our patients.

When I’m deciding what to use for first-line HCC, lenvatinib or sorafenib [Nexavar], I think about the side effects the patients will be able to tolerate, like high blood pressure, hand-foot-skin reaction, diarrhea, and proteinuria. I also think about the underlying liver function. I want to make sure that whatever I’m treating them with, they’re going to be able to tolerate it. I also consider their symptoms. Patients who have a lot of pain from their cancer and receive a response from lenvatinib, it would certainly be beneficial to use that treatment and alleviate their symptoms.

The patient in our case has alcoholic liver disease and is continuing to drink 3 to 4 drinks a day. Many of these patients that come in don’t want to quit drinking; however, I do counsel them that it is in their best interest to quit. The reason, again, is these patients have underlying liver disease, and if it worsens, it’s going to limit our cancer treatment options; it will affect their overall survival [OS]. At this point, quitting alcohol is the most important thing they can do to stay functional and allow us to treat this cancer. The other thing I remember is that many of these patients have been drinking for years, so I ask them carefully about symptoms of alcohol withdrawal in the past. If they exhibited those symptoms, I try to get them in with an addiction specialist, so that we can safely get them off alcohol without tremors, seizures, or life-threatening reactions.

The patient’s cirrhosis is Child-Pugh A, but we do have to be careful to take his liver disease and monitor him for issues that are going to make his liver disease worse and limit his cancer treatment. If he has low platelets, fewer than 150, and if he has signs of portal hypertension, we can get a FibroScan or transient elastography; we don’t need to do an endoscopy. However, most patients with cirrhosis need to have an upper endoscopy to screen for varices. This is very important because as their liver disease and cancer progress, this will put them at risk for variceal bleeding. We need to know whether they have varices to be able to put them on beta-blockers for primary prophylaxis.

Additionally, many patients with liver disease are not well nourished and may develop muscle wasting. We know that with liver disease and cancer, muscle wasting is a bad prognostic indicator. We can prevent muscle wasting by improving his protein intake and exercise, which will increase his OS. I discuss a lot with them: small frequent meals, making sure they’re getting enough protein—1.2 to 1.5 g per [kg] daily, including a bedtime snack with protein to maintain muscle mass.

The other thing we want to watch for are decompensations, like development of ascites that may require diuretics or development of hepatic encephalopathy, which may affect their thinking, clarity, and sleep. These people usually present and come in, saying they have insomnia, which is related to encephalopathy. We need to treat to maintain their quality of life and keep them out of the hospital.

This patient, unfortunately, did have progression on lenvatinib after 8 months, and had to stop therapy. For those patients, we then think about doing second-line therapy. Now we have a few treatment options for second line: the immunotherapy [I-O] nivolumab [Bavencio], is currently being approved for second-line treatment in patients with advanced HCC. It was predominantly studied in patients after sorafenib, but it doesn’t require sorafenib as part of its approval. Pembrolizumab [Opdivo], another I-O, has already been submitted to the FDA for approval for second-line treatment.

For patients that failed sorafenib, regorafenib [Stivarga] is an option. Regorafenib was studied in patients who tolerated sorafenib at half dose at least—400 mg per day for 20 to 28 days. We also have cabozantinib [Cabometyx] as a second-line option and, in some patients, could even work third line. We actually have several treatment options that we can offer.

Unfortunately, many patients with advanced HCC, by the time they’ve progressed on first line or are intolerant, have a worsening performance of their liver function, which many preclude them from being able to tolerate second-line treatment. It seems that only 50% to 60% of patients with advanced HCC make it to second-line treatment because of progression.

We’re in an exciting time for systemic treatment in HCC right now. It’s amazing to think that until 11 years ago, we had no systemic treatment options, and thereafter, only one. Now we have a myriad of options, and we’re trying to figure out what the best first-line and second-line treatment options are for patients. We’re also looking at various sequence therapies—that’s a big discussion going on. There’s also a multitude of studies ongoing about combination treatment—tyrosine kinase inhibitors with I-O, which could offer better OS and overall response rate. We really have changed what we’ve been able to offer our patients with HCC. It’s amazing that we now have systemic treatment, keeping people with metastatic disease alive for 15, 20, 26 months, or longer.

Transcript edited for clarity.

A 77-Year-Old Male With Unresectable HCC and Extrahepatic Involvement

• History and physical exam
  • An otherwise healthy, 77-year-old Caucasian male with a history of alcohol use
  • Presented to his PCP complaining of abdominal pain, fatigue and an unexplained 10-lb weight loss
  • Currently consumes 3-4 alcoholic drinks per day
  • ECOG PS 0
• Imaging
  • CT scan: 4.5-cm hepatic lesion with arterial hypervascularity, portal venous washout, and a pseudocapsule indicative of hepatocellular carcinoma; no evidence of vascular invasion
  • Bone scan: left-sided iliac mass (3.1 cm)
  • Chest CT: clear
• Diagnosis: unresectable HCC with extrahepatic involvement
  • BCLC stage C
  • Child-Pugh A
  • AFP Level: 3548.4 ng/mL
  • Weight: 72 kg
• Lenvatinib 12 mg QD was initiated.
  • He experienced modest weight loss and reported loss of appetite for which he was referred for nutritional therapy
  • Imaging at 16 weeks: partial response (0.5 cm)
  • 8 months after initiation of therapy: treatment discontinued due to disease progression