[ESMO 2025] ‘Datroway offers new alternative for triple-negative breast cancer unresponsive to immunotherapy’

BERLIN, Germany – By Hong Sook / Korea Biomedical Review correspondent -- A new first-line treatment approach is being introduced for triple-negative breast cancer (TNBC) patients who cannot use immunotherapy drugs.

AstraZeneca's antibody-drug conjugate candidate Datroway significantly improved overall and progression-free survival in the TROPION-Breast02 trial, positioning it as a potential new alternative to standard cytotoxic chemotherapy.

At ESMO 2025, researchers reported these findings, which drew immediate applause. These results are clinically significant, as no other treatment has extended survival in triple-negative breast cancer patients who are not eligible for immunotherapy.

“This study, which included patients in countries where immunotherapy is unavailable or unapproved, as well as those who relapsed after immunotherapy, has filled a real therapeutic gap,” Professor Jung Kyung-hae of the Department of Medical Oncology at Asan Medical Center told Korea Biomedical Review at the site of the ESMO 2025 last week. “The confirmation of significant survival extension even in poor-prognosis patients who relapsed within six months post-surgery represents a ‘practice-changing’ result.”

Professor Jung Kyung-hae of the Department of Medical Oncology at Asan Medical Center discussed the implications of Datroway in triple-negative breast cancer treatment during an interview with Korea Biomedical Review.

Question: Following the presentation of the TROPION-Breast02 study results at ESMO 2025, the applause lasted longer than expected. Why did healthcare professionals worldwide applaud this clinical trial?

Answer: Applause at conferences typically signals the presentation of research results with potential to alter clinical practice, such as the TROPION-Breast02 study, which reports meaningful benefit for patients.

Triple-negative breast cancer (TNBC) is a highly aggressive subtype, lacking the targetable molecular features seen in other breast cancers. TNBC represents about 10 to 15 percent of all breast cancer diagnoses, making it a minority group among breast cancer cases.

TNBC patients often experience rapid recurrence, typically within one to three years after surgery. For those with recurrent TNBC, treatment options beyond cytotoxic chemotherapy are limited and often ineffective.

In this context, the introduction of the immune checkpoint inhibitor pembrolizumab (Keytruda) as a new treatment option several years ago was significant, as it improved median overall survival (OS) for eligible patients from the previous standard to approximately 2 years. However, immune checkpoint inhibitors are only prescribed for patients whose tumors test positive for the PD-L1 protein; this group comprises fewer than half of all triple-negative breast cancer patients.

Ultimately, patients ineligible for immunotherapy have a median OS of approximately 12–13 months. Even among those in relatively good condition who qualify for clinical trials, the typical survival duration is only about 16–18 months.

Immunotherapy may trigger the immune system to attack normal cells, sometimes leading to thyroid dysfunction that requires lifelong medication.

Patients with autoimmune diseases can't receive immunotherapy, as it may worsen their conditions.

For these reasons, only about 30 percent of all triple-negative breast cancer patients in actual clinical practice are able to use immune checkpoint inhibitors. However, in Korea, insurance coverage for these treatments varies, so actual access depends on individual circumstances.

Often, patients begin treatment urgently only to stop due to financial issues, leading to recurrence. Even effective treatments can be unaffordable without insurance, leaving cytotoxic chemotherapy as the only option.

Q: What is the significance of the TROPION-Breast02 study for patients with triple-negative breast cancer who are ineligible for immunotherapy?

A: In Korea, sacituzumab govitecan (sold as Trodelvy) has already been approved for triple-negative breast cancer, and reimbursement coverage is available starting from second-line treatment. However, the patient population included in the TROPION-Breast02 study warrants closer examination.

This study included patients who previously had almost no treatment options: those who were PD-L1 negative or had underlying conditions making immunotherapy impossible, patients from countries where immune checkpoint inhibitors are not even approved, and patients who relapsed after using immune checkpoint inhibitors.

Most clinical trials exclude patients in poor condition to demonstrate efficacy. In contrast, this study enrolled all patients, including those with a very poor prognosis who relapsed within six months after surgery.

Researchers directly compared Dartroway with cytotoxic chemotherapy in these patients and found that progression-free survival (PFS) was significantly prolonged, and overall survival (OS) was extended to nearly 2 years.

This treatment arguably demonstrates the first increase in overall survival (OS). The study’s most significant implication is that it now offers a new, effective treatment to patients who previously had no option besides cytotoxic chemotherapy.

Q: For PD-L1-positive triple-negative breast cancer patients, which treatment should be used first: an immunotherapy or a TROP2-targeted ADC?

A: For PD-L1-positive triple-negative breast cancer patients, the current principle is to prioritize immunotherapy (such as Keytruda), which has the strongest evidence and sufficient clinical research. However, even in this case, efficacy decreases as treatment progresses to subsequent lines. In Korea, immunotherapy agents approved for PD-L1-positive patients are already available, so they should be considered first.

Q: At this ESMO meeting, Trodelvy also presented a study showing improved PFS as a first-line treatment for triple-negative breast cancer. So, what are the key considerations for prescribing Trodelvy vs. Datroway in actual clinical practice?

A: Ultimately, the key factors are the approved indications and insurance coverage. If the approval scope includes patients who relapse within six months, Datroway could effectively become the sole treatment option for patients with early-relapsed triple-negative breast cancer.

Furthermore, for patients with high tumor burden or those requiring rapid tumor shrinkage, Datroway is likely to be the preferred choice. Its longer dosing interval of once every three weeks also reduces the burden of clinic visits for patients, which is an advantage.

From an adverse reaction management perspective, clinicians can clearly distinguish the two drugs. While rare, Datroway can cause abnormalities on the eye surface, so patients should avoid contact lenses and use artificial tears frequently. Additionally, oral ulcers may develop; therefore, clinicians recommend a steroid mouthwash as a preventive measure. In practice, doctors advise these preventive steps alongside the prescription. Furthermore, because Datroway shares the same payload structure as Enhertu, clinicians must stay alert for interstitial lung disease (ILD) adverse reactions.

Trodelvy frequently causes diarrhea as an adverse reaction, and in some cases, doctors cannot proceed with treatment on schedule due to neutropenia. When this occurs, clinicians must use granulocyte colony-stimulating factor (G-CSF). The short-acting formulation requires two to three days of consecutive administration, while the long-acting formulation is expensive. Insurers do not cover the long-acting G-CSF for preventive purposes, imposing a financial burden even when patient safety absolutely demands its use.

Professor Jung Kyung-hae

Q: For some triple-negative breast cancer patients ineligible for immunotherapy, if HER2 expression is confirmed as even slightly positive (1+ or 2+), Enhertu, approved for HER2-low expression, can be prescribed. Could the results of the TROPION-Breast02 study lead to changes in future treatment strategies?

A: (In breast cancer), treatment sequence will be an important research topic going forward. For triple-negative breast cancer patients who are PD-L1 negative and thus have no options beyond cytotoxic chemotherapy, Enhertu can be used domestically if they are confirmed to have HER2-low expression.

However, the proportion of HER2-low patients is much lower in triple-negative breast cancer patients than in hormone receptor-positive breast cancer patients, so the number of patients who can actually use Enhertu is limited.

Furthermore, while Enhertu targets HER2 and Dartroway targets TROP2, both agents share the same payload structure. Consequently, if a patient who has already used one ADC (antibody-drug conjugate) with this payload structure subsequently receives another ADC, the therapeutic effect may diminish.

Consequently, it is difficult to expect the high response rates seen in the recently published study (if a patient treated with Enhertu subsequently receives Datroway). This is a critical aspect that must be addressed in future treatment sequence studies.

Of course, if no alternatives exist, physicians might consider trying another ADC drug sequentially. However, in practice, economic burdens or regulatory approvals could influence this decision. At this point, for first-line treatment, Datroway—which has clearly demonstrated an improvement in overall survival (OS)—is likely the preferred initial choice.

Q: Finally, what are your views regarding patient access in the context of emerging TROP2-targeting ADC anticancer drugs for triple-negative breast cancer patients?

A: Ultimately, reimbursement status is key. In Korea, the patient copayment rate is 5 percent. This means rare cancers with few patients face a relatively low financial burden, leading to faster reimbursement. However, cancers with large patient populations, like breast or lung cancer, face a structure where reimbursement is difficult to obtain.

From the patient's perspective, rather than waiting for a 10 million won ($6,988) treatment that isn't covered, it might be better to accept a slightly higher out-of-pocket cost to access it sooner. Patients simply don't have the time to wait for coverage before using a new drug.

When the combination therapy of trastuzumab + pertuzumab + docetaxel first became available for HER2-positive breast cancer patients, it was not covered. Administering six cycles costs approximately 40 million won. Later, pertuzumab, previously non-covered, was adjusted to a 30 percent selective coverage rate, reducing the patient burden to about 5 million won. Even this level of change makes patients feel they have broader treatment options.

Currently, the average age of breast cancer onset in Korea is around the early 50s. Patients who live a little longer can see their children get married and even see their grandchildren born. The hardest situation is when they can't do that, and the thought that their family couldn't afford treatment due to financial burden feels like a nail driven into their heart.

Society's understanding of the necessity for selective coverage is also needed from a national fiscal perspective. While the position requesting a lower copayment rate when selective coverage is applied is understandable, viewed another way, it could ultimately result in reduced treatment opportunities for other patients who need them. Ultimately, it is more realistic to apply selective coverage quickly, even partially, rather than having patients miss their treatment window while waiting for full coverage.