“Immunotherapies take lead in liver cancer treatment"

[ESMO Asia 2022] Professor Joong-Won Park, Division of Gastroenterology, National Cancer Center Korea

Immunotherapy+ Immunotherapy combination introduced to the scene... reduced risk of toxicity and bleeding

Price of drug Imjudo key focus of attention... will limit patient options if its reimbursement is delayed

The lack of later-line therapy options remains the biggest barrier to the use of immuno-oncology drugs

“Immuno-oncology drugs have brought great advances in the treatment of unresectable advanced hepatocellular carcinoma.

 

However, the unfortunate fact is that these are not well used in the field due to lack of later-line options.” Professor Joong-Won Park, Division of Gastroenterology, National Cancer Center Korea, said so to Dailypharm at the ‘ESMO Asia Congress 2022’ that had been held in Singapore.

 

On the same day, Professor Park introduced the latest research trends in liver cancer treatment at a session held on ‘Patient care in hepatobiliary cancers: Emerging therapeutic approaches and remaining unmet needs.’ According to Professor Park, the treatment paradigm for unresectable advanced liver cancer (hepatocellular carcinoma) has been evolving quickly with the introduction of immuno-oncology drugs.

 

Roche’s ‘Tecentriq’ had been granted as a first-line treatment for HCC in combination with the VEGF inhibitor ‘Avastin.’ It became the first immunotherapy approved for the systemic treatment of liver cancer.

 

Following the combination, AstraZeneca’s immuno-oncology drug Imfinzi’ was also approved in combination with ‘Imjudo,’ another immuno-oncology drug with a different mechanism of action.

 

The Imfinzi+Imjudo combination was approved in the US in October and is expected to be soon introduced to Korea as well.

 

Through the STRIDE regimen (single dose of Imjudo as an initial dose followed by Imfinzi every four weeks), the Imfinzi+Imjudo combination improved the effect while minimizing safety risks.

 

Another benefit of using Immuno-oncology drug combinations is that patients can worry less about the risk of hepatotoxicity that arises from the use of TKIs or bleeding from Avastin.

 

Professor Park said, “We consider bleeding risk an important factor when selecting primary treatments.

 

Patients with hepatic-portal hypertension must be tested for risk of hemorrhage.

 

Slight concerns (adverse event) remain in the use of Imjudo in the Imfinzi+Imjudo combination, but it is only administered once, so if the patient well passes that period, the combination is well-tolerated." Its effect was also positive.

 

According to the HIMALAYA Phase III trial, the Imfinzi+Imjudo combination using the STRIDE regimen recorded a median overall survival (mOS) of 16.4 months and reduced the risk of death over Nexavar by 22%.

 

At 36 months of follow-up, the proportion of patients that reached OS in the Imfinzi+Imjudo group and Nexavar group was 30.7% and 20.2%, respectively, demonstrating an improvement in long-term survival with the use of Imfinzi+Imjudo.

 

The Asian (excluding Japan) subanalysis results of the HIMALAYA trial were also disclosed at the ESMO Asia Congress.

 

In Asians, the mOS of Imfinzi+Imjudo was 16.5 months, consistent with the global data.

 

At 35 months, the OS was 32.2% in the Asian group.

 

Professor Park explained, “It is encouraging that the data showed positive results in Asians, as we have a higher prevalence of hepatitis B than in the West.

 

Immuno-oncology drugs came to the fore in this year’s guideline for HCC treatment in Korea.

 

According to the '2022 Practice Guideline for Diagnosis and Treatment of Hepatocellular Carcinoma’ that was published by the Korean Liver Cancer Association, the Tecentriq + Avastin and Imfinzi + Imjudo combinations received A1 recommendations.

 

This is the first time an immuno-oncology drug received a priority recommendation, overtaking Nexavar, which had been the standard treatment for liver cancer for a long time.

 

The biggest challenge that remains for the use of these immunotherapy combinations is in receiving reimbursement.

 

The key lies in how fast the Imfinzi + Imjudo combination will be able to receive reimbursement after it is introduced to Korea.

 

The high prices of Tecentriq and Avastin had been the biggest barrier to their reimbursement in HCC.

 

Fortunately, the introduction of Avastin biosimilars after the expiry of Avastin's patent lowered the drug price and allowed progress in their reimbursement.

 

On the other hand, Imfinzi's partner, Imjudo, is expected to have a higher price barrier because it is a new immuno-oncology drug.

 

The later-line therapies following the use of immunotherapy-based regimens also remain a barrier.

 

The guidelines recommend physicians and patients consider the use of 6 drugs including Nexavar, Lenvima, Stivarga, and Cabometyx.

 

However, in practice, the only realistic option is to use Nexavar without reimbursement.

 

Lenvima is not approved for use in the second line in Korea.

 

In the case of Stivarga and Cabometyx, they are only allowed for use after using Nexavar in the first line.

 

Professor Park said, “Using Nexavar or Cabometyx in the second line is not an issue in the US or in Japan.

 

It is even covered by insurance there.

 

However, in Korea, reimbursement is strictly set for each line of therapy, therefore, it is difficult to use new drugs that are introduced in Korea due to the lack of later-line options.

 

Using the recommended drugs in the later line as in the US or Japan is off-label and illegal or rejected from reimbursement.

 

This is one of the biggest barriers in HCC treatment in Korea.”