"Enhertu gets expanded indication to treat lung cancer"

Ahn Myung Ju, Professor of the Division of Hematology-oncology in the Department of Medicine at Samsung Medical Center

Demonstrated efficacy in HER2 mutant lung cancer, which previously had failed clinical trials with conventional treatments

More effective than coventional treatments in terms of response rates and DOR

Ahn Myung Ju, Professor of the Division of Hematology-oncology in the Department of Medicine at Samsung Medical Center

“Previously, patients could only use Enhertu by participating in clinical trials conducted in tertiary general hospitals.

 

Current approval in South Korea will provide a new treatment option for patients with HER2 mutant metastatic non-small cell lung cancer (NSCLC).

 

Brain metastasis is common in lung cancer patients.

 

Because Enhertu demonstrated a response rate of 50% in patients with brain metastasis, it is clinically significant.” During a recent meeting with Daily Pharm, Ahn Myung Ju, Professor of the Division of Hematology-oncology in the Department of Medicine at Samsung Medical Center, highly regarded the clinical value of Enhertu (ingredient: trastuzumab deruxtecan).

 

Enhertu, an antibody-drug conjugate (ADC) jointly developed by Daiichi Sankyo and AstraZeneca, has been approved for the treatment of HER2-positive breast cancer and gastric cancer.

 

As Enhertu demonstrated to be effective in HER2 mutant NSCLC and HER2-low breast cancer, its indication was expanded in May.

 

HER2 mutant NSCLC is a rare cancer that occurs in about 2-4% of patients with NSCLC.

 

Previously, the treatment of this cancer with chemotherapy and immunotherapy for cancer was limited, and HER2-targeted therapy showed inconsistent results.

 

Therefore, there has been an unmet need for an effective treatment option to increase the survival in patients.

 

Previously, several targeted treatment options, such as Hanmi Pharm’s poziotinib, were tested for the treatment of HER2 mutant NSCLC but failed to demonstrate efficacy.

 

Therefore, Enhertu is likely to provide new hope to patients with HER2 NSCLC, which is categorized as a rare cancer.

 

Ahn said HER 2 mutation gained attention in NSCLC after the availability of next-generation sequencing (NGS) testing and targeted therapies like Enhertu.

 

It will provide a new treatment opportunity to patients with NSCLC.

 

Enhertu is approved in South Korea based on phase 2 trials Enhertu is an ADC that targets HER2 mutations by linking an antibody to a payload that destroys tumor cells.

 

This treatment works by binding antibodies to specific antigens, triggering an Antibody-Dependent Cellular Cytotoxicity (ADCC) reaction, and allowing the payload to enter tumor cells and exit through their membranes.

 

This mechanism results in a bystander effect, enabling the destruction of cancer cells, including those without HER2 mutations, demonstrating its anti-tumor efficacy.

 

Enhertu is effective in various diseases, including breast cancer, gastric cancer, colorectal cancer, and NSCLC.

 

In DESTINY-Lung02 study, Enhertu demonstrated antitumor response to the second-line treatment of HER2 mutant metastatic NSCLC.

 

This study evaluated the efficacy and safety in patients with advanced, unresectable, or metastatic NSCLC who have previously been treated with systemic therapy, including platinum-based chemotherapy, more than once.

 

The clinical results demonstrated that Enhertu had confirmed ORR of 49%, complete response (CR) of 1%, and partial response (PR) of 48%.

 

The mean duration of response (DOR) was 16.8 months.

 

“Previously, the second-line treatment, docetaxel, showed a response rate of only 10-15% and a median progression-free survival (PFS) of just 5-6 months.

 

In contrast, Enhertu showed a response rate of 50% and a durable response period lasting up to 16 months.

 

Moreover, brain metastasis is commonly found in lung cancer, and Enhertu has demonstrated an intracranial objective response rate (IC-cORR) of over 50%, even in patients with brain metastasis,“ Ahn said.

 

“Kadcyla, previously used for HER2-positive breast cancer, showed a response rate of over 50% in non-small cell lung cancer (NSCLC) but had limitations due to the short duration of response.

 

In this context, Enhertu has recently gained attention for demonstrating efficacy in HER2-mutated metastatic NSCLC patients,“ Ahn said.

 

”Although it’s a phase 2 single-arm study, Enhertu demonstrated better outcomes than data from existing medications, warranting consideration for reimbursement,“ Ahn added.

 

"Enhertu use will be greater" in HER2 NSCLC In the case of metastatic non-small cell lung cancer (NSCLC) with HER2 mutation, it represents about 2-4% of all NSCLC cases.This cancer type is characterized by adenocarcinoma histology, prevalence in non-smokers and females, and a higher incidence among East Asian populations, including Japan and Korea.

 

Additionally, it exhibits a higher rate of brain metastases.

 

HER2 abnormalities are categorized into ‘gene mutations,‘ ‘gene amplifications,‘ and ‘protein overexpression.‘ In most cancers, such as gastric cancer and breast cancer, HER2 abnormalities mainly manifest as an overexpression of the HER2 protein.

 

Previously, HER2 overexpression gene abnormalities were generally considered to not play a significant role in NSCLC.

 

First-generation platinum-based chemotherapy has traditionally been the standard treatment for HER2 mutant non-small cell lung cancer.

 

Recently, combination therapies of platinum-based chemotherapy and immunotherapy for cancer have also been employed.

 

However, non-smokers are known to have a poorer response to immunotherapy for cancer, leading to worse prognosis.

 

“So far, in HER2-mutated metastatic non-small cell lung cancer (NSCLC), drugs like Giotrif (afatinib), which is developed to target Epidermal Growth Factor Receptor (EGFR) mutations, have been used, but their response rates have been low, around 10%,“ Ahn said.

 

“Additionally, poziotinib showed a better response rate of approximately 27%, but its use has been challenging due to significant toxicity and side effects,“ Ahn added.

 

Ahn said that Enhertu will bring many changes to the treatment of NSCLC.

 

“In the United States, Enhertu is indicated for the treatment of HER2 mutant metastatic NSCLC with the U.S.

 

FDA approval, and it is widely used with reimbursement coverage.

 

Even in Europe with stringent standards, non-small cell lung cancer patients are strongly recommended to undergo HER2 mutation testing, and those with HER2 mutations are advised to use Enhertu,“ Ahn said.

 

“It is unfortunate that patients cannot afford the monthly cost of approximately 7 to 8 million won for Enhertu, which allows them to maintain their daily lives for over a year.

 

Therefore, it would be beneficial if the government explores various measures, such as selective reimbursement, to alleviate the financial burden on patients, even if it means slightly increasing the portion they pay out of pocket,“ Ahn emphasized.