“Liver cancer option expands, but needs further evidence”

An interview on Professor Kim Doyoung of Gastroenterology Department at Severance Hospital

Choosing treatment option is based on ‘evidence,’ high hopes for immunotherapy

Stivarga coverage should also cover patients in Child-Pugh class B7 like Nexavar

Professor Kim Doyoung

When a new drug development in a specific area is sluggish, there are two prominent reasons why; either the disease area has low marketability or the drug development itself for the disease is very difficult.

 

In the latter case, a new drug gets an obvious spotlight when it is released to the market.

 

Liver cancer (hepatocellular carcinoma) would be a good example.

 

For over a decade, Nexavar (sorafenib) was technically the only option to be used on liver cancer patients.

 

But now, the disease specialists have heightened anticipation on other options to come.

 

Stivarga (regorafenib) entered the market as a second-line treatment, and Lenvima (lenvatinib) was added as another first-line treatment option at the same level as Nexavar.

 

In the U.S., Tecentriq (atezolizumab) and Avastin (bevacizumab) were approved as a combination therapy recently, which newly added an immunotherapy as an option.

 

The situation in Korea is also taking a step at a time.

 

Early this year, the healthcare reimbursement standard on Nexavar has been adjusted to grant the benefit on patients in Child-Pugh scoring of class B7, a severe case of the disease.

 

The change raised the usability of the pharmaceutical treatment in liver cancer.

 

Daily Pharm interviewed Professor Kim Doyoung of Gastroenterology Department at Severance Hospital and spoke of the hepatocellular carcinoma treatment strategy with more options available now.

 

-First of all, what does expanded coverage on Nexavar mean for a healthcare provider?

 

The patients in Child-Pugh class B7 were considered somewhat of ‘grey area.’ The patient’s liver function level is comparatively close to normal state, but they have risk of developing ascites or jaundice.

 

The patients stuck in the middle did not have a clear answer to choose as a treatment option.

 

These patients need treatment without building liver toxicity.

 

And Nexavar, as proved in various evidences, demonstrates less liver toxicity.

 

Basically, the liver cancer patients hopeless without a proper treatment option can now be treated with Nexavar.

 

-What are some points to consider—like dosage control or administration suspension—when prescribing Nexavar on patients in Child-Pugh class B7? There are no specific precautions to consider.

 

In the GIDEON study that produced global real-world data (RWD) from over 3,000 intent-to-treat participants, Nexavar barely showed much difference between patient groups in Child-Pugh class B7 and Child-Pugh class A.

 

Regardless of class A6 or class B7, normal dosage is recommended but reduced dosage is recommended for patients showing adverse reaction.

 

The dosage does not have to be adjusted from the beginning.

 

-Would the transarterial chemoembolization (TACE) have some changes as Nexavar is now reimbursed and the systemic anticancer therapy option has expanded?

 

Would it be safe to assume this is the period when healthcare providers are trying to reach a consensus on the recommended frequency of TACE and treatment ceasing point?

 

Due to the coverage expansion, some may think of using Nexavar when the patient’s Child-Pugh scoring gets worse after repeated TACE.

 

But the patient’s survival rate would worsen if the Nexavar administration timing is delayed and liver function starts failing according to Child-Pugh scoring.

 

In fact, the talk of when to use systemic anticancer therapy on patients with failed attempt of TACE or refractory condition has continued for over a decade.

 

Although some of the consensus among the healthcare providers has been documented, but it would take a while for the medical practice environment to accept the change and apply it.

 

After practicing TACE for many times, I can see whether or not the patients either should continue on with TACE.

 

Many healthcare providers would agree with me.

 

The decision to continue with TACE should be made promptly but carefully, and switch to another option, if need be.

 

At some point, there was a talk on how beneficial it is to quickly switch to systemic anticancer therapy after TACE.

 

But the argument lacks sufficient evidence in improving the survival rate.

 

-Does that mean, in some cases, there is a concerning factor when following up promptly with a systemic anticancer therapy after TACE?

 

In the past, when Nexavar was the only option of systemic therapy for treating liver cancer, the healthcare providers regarded switching to a systemic anticancer therapy after TACE as a ‘last resort.’ So the treatment switch was not fast enough and it was worrying.

 

But now the healthcare providers seem to agree more that a systemic anticancer therapy is not a ‘last resort,’ as Nexavar is prescribed to patients with comparatively good functioning liver, and also because a follow-on drug Stivarga is commercialized.

 

-As Nexavar is the only systemic anticancer therapy with coverage for patients in Child-Pugh class B7.

 

These patients do not have a choice in later-line treatment with coverage Stivarga’s global REFINE study conducted in a real-world practice conditions in 1,000 patients, diagnosed with unresectable hepatocellular carcinoma, included many of patients in Child-Pugh class B and other more severe cases.

 

Regardless, the study confirmed improved efficacy against Stivarga in global Phase III RESOURCE trial.

 

Based on these findings, Stivarga’s coverage should be expanded to patients in Child-Pugh class B7 for them to resume treatment after Nexavar.

 

-Recently, a combination of immunotherapies was passed by the U.S.

 

health authority.

 

What is your expectation on it?

 

I expect that the prospective competitor of Nexavar to be the combination of immunotherapies.

 

To be honest, I had a great expectation on Opdivo (nivolumab) for treating patients with hepatocellular carcinoma, because its clinical trial had two patients who demonstrated complete response (CR).

 

But using it in the actual practice, the response rate was not as good as I expected.

 

And apparently, Tecentriq combination has exhibited improved result than Nexavar, and it looks ‘good’ at face value.

 

But we need to watch if the combination therapy can show better efficacy in uncontrolled real-world practice conditions.

 

There is also the catch—the patients have to frequently visit the hospital to receive the injection.

 

And of course, the biggest problem of expensive price is still unresolved.