"Trodelvy gives new hope for triple-negative breast cancer"

A new ADC drug

Dr. Aditya Bardia, Professor at UCLA, and Dr. Sohn, Joo Hyuk, Professor at Yonsei Cancer Hospital

ADC Trodelvy has improved PFS·OS·ORR in clinical trials, which were the basis for approval

"Unmet needs are high for triple-negative breast cancer treatment…Trodelvy will play a significant role"

Triple-negative breast cancer refers to a breast cancer that is negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2).

 

It is a rare cancer that accounts for about 12-15% of all breast cancer.

 

This cancer tends to be aggressive and has a high risk of metastasis and recurrence, leading to poor diagnosis.

 

However, patients with this type of cancer have relied on cytotoxic anticancer medicines, the first-generation cancer treatment.

 

They were unable to benefit from the latest cancer treatments, such as antihormone therapies and targeted cancer therapies, because all the receptors that could be targeted were negative.

 

Trodelvy, a Trop-2 protein targeting antibody-drug conjugate (ADC), has opened a road for a new treatment for patients with metastatic triple-negative breast cancer.

 

Trop-2 protein is a cell membrane antigen that is highly expressed in breast cancer and overexpressed in over 90% of triple-negative breast cancer.

 

Trodelvy binds with Trop-2 protein and releases cytotoxic agents inside the cancer cells.

 

It has the advantage of minimizing damage to healthy cells while maintaining the beneficial effects of targeted cancer therapies and cytotoxic anticancer medicines.

 

In the multinational phase 3 clinical study, Trodelvy significantly improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR).

 

In May, Trodelvy obtained approval from the Ministry of Food and Drug Safety (MFDS) and launched in South Korea.

 

(From the left) Dr.

 

Sohn, Joo Hyuk, Professor in the Department of Internal Medicine at Yonsei Cancer Hospital·Dr.

 

Aditya Bardia, Professor in the Department of Medicine at UCLA Health Jonsson Comprehensive Cancer Center.

Daily Pharm met with Dr.

 

Aditya Bardia, the first author of 'ASCENT' clinical study and Director of Translational Research Integration and Professor in the Department of Medicine at UCLA Health Jonsson Comprehensive Cancer Center, and Dr.

 

Sohn, Joo Hyuk, Professor in the Department of Internal Medicine at Yonsei Cancer Hospital and Korean Cancer Study Group (KCSG)'s Head of Breast Cancer Committee, to look at recent therapy trends for triple-negative breast cancer and clinical use of Trodelvy.

 

Q.

 

For a long time, there has been a high demand for new treatment options for triple-negative breast cancer.

 

What is the reason for the difficulty in developing treatments? [Dr.

 

Bardia] Triple-negative breast cancer shows the most aggressive characteristic among breast cancers, and it occurs in relatively young patients.

 

Cytotoxic anticancer medicines are mainly used for the treatment because it is difficult to use targeted therapies due to potential therapeutic targets such as ER, PR, and HER are all negative.

 

The problem is anticancer agents do not work efficiently in patients with metastatic cancer.

 

Such difficulties contributed to high unmet needs for new drugs among breast cancers.

 

[Dr.

 

Sohn] Triple-negative breast cancer can be categorized as a diagnosis of exclusion.

 

It refers to all breast cancer types that do not test positive for hormone receptor or HER2.

 

Within the type, subtypes also exist.

 

Therefore, the cancer does not exhibit consistent characteristics, posing difficulty in developing a generalized drug to be used for triple-negative breast cancer.

 

The number of patients is relatively small, and a biologically verified target has not been identified; therefore, a treatment has not been developed.

 

The disease itself shows aggressiveness, and patients tend to have poor diagnoses because anticancer chemotherapy that was developed decades ago is used.

 

Q.

 

What are the advantages Trodelvy for treating triple-negative breast cancer, where new drug development has been slow?

 

Dr.

 

Sohn, Joo Hyuk, Professor in the Department of Internal Medicine at Yonsei Cancer Hospital.

 

[Dr.

 

Bardia] Triple-negative breast cancer is negative for three receptors, ER, PR, and HER, but it does not entail that there are no receptors.

 

Trodelvy is a treatment that targets Trop-2 protein, which is known to be overexpressed in over 90% of triple-negative breast cancer.

 

Trodelvy can target cancer cells more efficiently than conventional standard therapies, showing superior effects.

 

It has been designed to affect less on healthy cells, lowering toxicity and side effects that patients experience.

 

[Dr.

 

Sohn] Targeted therapies to date have used oncogenes that affect the progression and expansion of cancer as a target.

 

However, Trop-2, which Trodelvy targets, is only a receptor expressed on the cell surface.

 

Trodelvy is the first medicine to demonstrate the concept that a therapy targeting receptor expressed on cancer cell surface instead of an oncogene can be used to destroy cancer cells.

 

In other words, it is meaningful that we have confirmed that identifying a receptor expressed on a cancer cell surface can lead to the development of a therapy.

 

Q.

 

According to the phase 3 ASCENT study, Trodelvy improved OS, PFS, and ORR statistically significantly compared to anticancer chemotherapies.

 

What do these results indicate?

 

[Dr.

 

Bardia] Trodelvy had twofold longer OS than anticancer chemotherapy, extending patients' life expectancy.

 

It also improved symptoms that affected patients' quality of life due to cancer, such as pain, thereby improving the quality of life during survival.

 

The result gives patients hope to live a longer and better quality of life.

 

[Dr.

 

Sohn] The last drug to demonstrate the benefit of OS in triple-negative breast cancer was Halaven, released 10-20 years ago.

 

New drugs, such as immunotherapy for cancer and PARP inhibitors, have been introduced.

 

However, they are designed to target particular patient groups, such as PD-L1-positive patients and BRCA-mutation patients.

 

Other than these, cytotoxic anticancer medicines are the only treatment that can be used in all patient groups with triple-negative breast cancer.

 

Therefore, the recent data showing extended OS is historically meaningful.

 

Patients are the only ones who can understand the differences in the number of months.

 

Q.

 

Has there been any change in clinical settings, including breast cancer treatment guidelines, since Trodelvy was introduced?

Dr.

 

Aditya Bardia, Professor in the Department of Medicine at UCLA Health Jonsson Comprehensive Cancer Center.

[Dr.

 

Bardia] The breast cancer guidelines of the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO) foremost recommend Trodelvy as a second-line treatment for metastatic triple-negative breast cancer.

 

In particular, Trodelvy has received a score of 5 on the ESMO-MCBS, a value-evaluation tool for anticancer medicines.

 

Out of 37 approved treatments for metastatic breast cancer, there have been only two medicines that received a score of 5 (Trodelvy and HER+/HER2- medicine, Ribociclib).

 

[Dr.

 

Sohn] Previously, the effect of standard therapies for the treatment of triple-negative breast cancer was not good.

 

When a first-line anticancer treatment had failed, the survival expectancy was only 7 months.

 

It is a great hope to introduce a new treatment with verified survival effects to patients.

 

Patients are welcoming treatments even if they are yet non-reimbursable.

 

Until now, clinical settings for triple-negative breast cancer have been challenging, but this medication is likely to resolve a long-standing issue.

 

Q.

 

What resources are most needed to improve treatment settings for triple-negative breast cancer in South Korea?

 

[Dr.

 

Bardia] What we need most is to introduce the most effective new drugs regardless of the situation.

 

We hope to enhance patients' survival duration and quality of life.

 

I know that due to non-reimbursement, patients have limited access to Trodelvy in South Korea.

 

I hope that National Health Insurance will be quickly applied and that access to Trodelvy in combination with other medicines will be granted.

 

[Dr.

 

Sohn] Patients who have private insurance or have financial well-being always choose Trodelvy.

 

Considering the clinical data, it is a must.

 

However, it is unfortunate that patients cannot use the medicine for economic reasons despite of the clinical evidence.

 

I hope that healthcare financing will be allocated to those in need so that no patients are left without access to life-saving medicines.

 

By reducing unnecessary medical spending and increasing resources for essential healthcare, South Korea can become a society that provides hope and easy access to new drugs for desperate patients.

 

Q.

 

What do you envision as the future approach to treating metastatic triple-negative breast cancer? [Dr.

 

Bardia] I was once interested in AKT and PI3CA mutations and conducted two accounts of phase 3 clinical studies.

 

However, I did not achieve fruitful outcomes.

 

We guessed that because triple-negative breast cancer is further characterized into many subtypes, targeting AKT and PI3K3CA mutations was not effective for triple-negative breast cancer.

 

Currently, treatments that target genetic mutations are limited to PARP inhibitors, which are offered as a first-line or second-line treatment to patients with BRCA mutations.

 

[Dr.

 

Sohn] Since recent studies to find new targets to treat triple-negative breast cancer are failing to demonstrate effectiveness, the remaining solution is likely to be the development of medicines targeting oncogene addiction.

 

I heard that 350 ADCs are currently under development.

 

New drug development is anticipated through studies about antibodies targeting cell surface receptors, cytotoxic agents, and linkers.

 

I hope there will be more research related to combination therapies of ADCs and cytotoxic anticancer agents.