'ADC' Enhertu, a Miracle Anticancer Drug Regardless of Cancer Type?

AZ-DS Jointly Developed ADC 'Enhertu'
Potential Efficacy in Uterine and Ovarian Cancers Beyond Breast Cancer
HER2-Targeted 'Tumor-Agnostic' Anticancer Drug Potential

The antibody-drug conjugate (ADC) anticancer drug 'Enhertu,' developed by AstraZeneca (AZ) and Daiichi Sankyo (DS), is generating expectations as a 'tumor-agnostic' anticancer drug that could be used across various cancers, beyond just breast cancer, as clinical results showing its efficacy in other cancers are being released one after another.

AstraZeneca-Daiichi Sankyo's antibody-drug conjugate (ADC) Enhertu (generic name: trastuzumab deruxtecan)
[Photo by Daiichi Sankyo Korea]

On the 27th of last month (local time), AZ announced that Enhertu demonstrated "clinically meaningful progression-free survival (PFS) and overall survival (OS)" in the Phase 2 'Destiny-PanTumor 02' clinical trial conducted on patients with various 'human epidermal growth factor receptor 2 (HER2)' expressing advanced solid tumors. PFS refers to the period during which cancer progression or recurrence does not occur, and OS refers to the total survival time of the patient. This trial involved patients with cervical cancer, endometrial cancer, ovarian cancer, cholangiocarcinoma, pancreatic cancer, and bladder cancer. However, detailed data were not disclosed. Specific PFS and OS figures are expected to be revealed later through academic conference presentations. In terms of safety, there were no significant changes compared to existing data.

With this, Enhertu is gaining attention as a treatment that can significantly extend patients' lives, following its notable anticancer effects on HER2-expressing cancers presented at the American Society of Clinical Oncology (ASCO) in June. The interim analysis presented at ASCO showed an objective response rate (ORR)?the primary clinical endpoint?of 37.1% among all participants and 61.3% in the 'IHC3+' group with HER2 overexpression. Particularly, substantial ORRs were observed in endometrial cancer (57.5%) and cervical cancer (50%). ORR indicates the proportion of patients whose tumor size shrinks or completely disappears, reflecting the drug's efficacy. At the presentation, discussions even raised expectations that Enhertu could evolve into a tumor-agnostic anticancer drug.

This potential for expanding to various cancer types is due to Enhertu targeting the HER2 protein. HER2, which sends signals inside cells to stimulate cancer growth, is known to be associated with higher risks of recurrence and metastasis as its expression level increases across the IHC 0, 1+, 2+, and 3+ stages. Conversely, targeting HER2 can inhibit cancer progression. HER2 protein overexpression mainly occurs in breast, stomach, lung, and colorectal cancers, so HER2-targeted therapies have been actively developed and commercialized for these cancers. Enhertu is an ADC created by combining the existing HER2-targeting antibody 'trastuzumab,' known as 'Herceptin,' with the cytotoxic payload 'deruxtecan' developed by Daiichi Sankyo. Like a missile, trastuzumab acts like radar to locate HER2 cancer cells, allowing the payload to attack only these cells, making it a next-generation anticancer drug with higher efficacy.

However, the cancer types included in this trial had HER2 expression but lacked approved targeted therapies. Due to reasons such as the belief that HER2 targeting alone was insufficient for anticancer effects, no approved treatments existed, resulting in significant unmet needs. Yet, Enhertu showing efficacy in HER2-expressing patients with these cancers is raising expectations for a tumor-agnostic anticancer drug. Obitna, Director of Clinical Development at Medirama, commented, "Given the promising results in cancers with high unmet needs, I agree with the potential for development as a tumor-agnostic therapy. However, while HER2 overexpression shows high potential, additional research is needed for IHC2+, and further studies and analyses on patient characteristics, such as cancer type and biomarkers, that could benefit therapeutically from Enhertu are necessary."

Meanwhile, Enhertu has become the most widely used drug in this field overseas, including in the United States, with expected sales of 320 billion yen (approximately 2.9 trillion KRW) this year, continuing market expansion. However, in South Korea, despite receiving approval from the Ministry of Food and Drug Safety last September for second-line treatment of HER2-positive breast cancer patients, it has yet to be covered by the National Health Insurance. Although it passed the first hurdle at the Cancer Disease Deliberation Committee after a re-examination in May, procedures such as the Drug Benefit Evaluation Committee remain pending. Consequently, patients have petitioned the National Assembly for rapid reimbursement, and this petition has been referred to the Health and Welfare Committee, with ongoing calls for swift insurance coverage.

This content was produced with the assistance of AI translation services.