[ESMO 2024] 'Silent Killer' Liver Cancer, Survival Chances Increased with Dual Use of Immuno-Oncology Drugs

5-Year Survival Rate Only 3% When Metastasis Detected
AZ's 'Imfinzi and Imuudo Combination Therapy'
5-Year OS Confirmed at 20%... Twice That of Existing Treatments
Approved Domestically but Health Insurance Coverage Remains Stalled

A study has found that about 20% of patients with terminal liver cancer, often called the 'silent killer' because it is usually detected only at an advanced stage due to the lack of clear symptoms, can achieve long-term survival when treated with a dual immunotherapy regimen. This marks a significant improvement compared to the previous 3% five-year survival rate for cases that had progressed to metastasis.

Professor Lorenza Rimassa of the Department of Medical Oncology and Hematology at Humanitas University in Italy presented the results on the 16th (local time) during the fourth day of the 2024 European Society for Medical Oncology (ESMO) conference in Barcelona, Spain, titled 'Five-year overall survival (OS) and OS by tumor response in the phase 3 HIMALAYA study of tremelimumab plus durvalumab in patients with unresectable hepatocellular carcinoma'. She stated, "The five-year survival analysis represents the longest follow-up among phase 3 studies in liver cancer, demonstrating an unprecedented long-term survival benefit with a 19.6% five-year survival rate," and emphasized, "This study continues to set new standards in liver cancer treatment, with one in five patients with unresectable liver cancer surviving for five years." Professor Rimassa was the first author of this study.

Liver cancer ranks as the second leading cause of cancer-related deaths in South Korea, highlighting the urgent need for improved treatments. However, because the cancer progresses without clear symptoms, only about 30% of patients are diagnosed at a stage where curative surgery or liver transplantation is possible. Consequently, the five-year survival rate is 39.3%, roughly half of the 72.1% average for all cancers. Moreover, in cases of distant metastasis where the cancer has spread to other organs, the survival rate drops to a mere 3.1%.

AstraZeneca's immuno-oncology drug 'Imfinzi'
[Photo by Korea AstraZeneca]

Various treatment methods have been proposed to overcome these challenges, but none have successfully balanced efficacy and safety. Nexavar was developed in 2008 but raised concerns due to its side effects, and Lenvima, developed later in 2018, also faced limitations in improving patient outcomes because of toxicity issues.

AstraZeneca (AZ) introduced a dual immunotherapy regimen combining tremelimumab and durvalumab (STRIDE regimen) as a new weapon against advanced or unresectable liver cancer. This approach boasts relatively lower risks of side effects such as bleeding and liver function deterioration while demonstrating long-term survival benefits.

The immune system in our body has the power to attack cancer cells, but cancer cells evade this by creating fake passes that disguise them as normal cells. Immunotherapy drugs disable these fake passes, enabling T cells, which act as soldiers in the immune system, to kill cancer cells effectively. Tremelimumab binds first to the programmed cell death protein (PD)-L1 among these fake passes, allowing T cells to recognize cancer cells as enemies. Durvalumab, on the other hand, binds first to CTLA-4 on T cells, preventing the fake pass protein CD80 created by cancer cells from functioning. The STRIDE regimen involves simultaneous administration of tremelimumab and durvalumab at the start of treatment, followed by regular dosing of tremelimumab to ensure both immunotherapies exert their effects.

The 5-year survival results of the 'Himalaya' study, a clinical trial of Imfinzi and Imudo combination therapy (STRIDE therapy) for liver cancer patients, presented at the 2024 European Society for Medical Oncology (ESMO) held in Barcelona, Spain, on the 16th (local time).
[Photo by Lee Chunhee]

The STRIDE regimen demonstrated sustained and stable efficacy over a long period through the HIMALAYA clinical trial. The initially reported median overall survival (mOS) was 16.4 months, successfully reducing the risk of death by 22% compared to Nexavar, the existing standard treatment and control group, which had a median survival of 13.8 months. OS refers to the duration from treatment initiation until death and is a key indicator for evaluating anticancer drug efficacy.

AZ has been releasing additional OS study results annually. At the two-year mark, the STRIDE group showed a 40.5% survival rate compared to 32.6% in the control group. At three years, the survival gap widened to over 10 percentage points, with 30.7% versus 19.9%. At four years, it was 25.2% versus 15.1%, and finally, at five years, the difference was maintained at 19.6% versus 9.4%. Notably, the five-year OS survival gap doubled, confirming a 24% reduction in the risk of death.

These results demonstrate that immunotherapy can provide long-term stable treatment by enhancing the immune system's ability to eliminate cancer cells. Additionally, the study confirmed safety benefits such as a lower risk of bleeding, which is common among liver cancer patients, due to the relatively mild side effects of immunotherapy alone.

Currently, the STRIDE regimen is recommended as the first-line standard treatment for advanced liver cancer by the National Comprehensive Cancer Network (NCCN) in the United States and is also approved domestically in South Korea. However, it is not yet covered by health insurance. In June, Korea AZ applied for insurance coverage for tremelimumab targeting liver and biliary tract cancers. Among the eight major countries worldwide (A8), insurance coverage for this regimen is applied in five countries, including the United States, Canada, and Japan. The company added, "Positive evaluations have been received from health technology assessments (HTA) in France and Spain, and we are awaiting reimbursement decisions."