The TROPION-Breast02 study presented at the European Society for Medical Oncology Congress 2025 (ESMO 2025) marks a new turning point in the treatment of triple-negative breast cancer (TNBC).

As the first antibody-drug conjugate (ADC) trial to significantly improve both overall survival (OS) and progression-free survival (PFS) in patients who cannot receive immunotherapy, it heralds a change in actual clinical practice.

At ESMO 2025, Professor Kyung-Hae Jung of Asan Medical Center emphasized that this study provides the first clinical evidence of survival benefit in a patient population that previously had no options beyond cytotoxic chemotherapy.

First Phase III study to improve Overall Survival...beyond cytotoxic chemotherapy dependence

TROPION-Breast02 is a Phase III clinical trial comparing Datroway(Dato-DXd) monotherapy with chemotherapy in 644 patients with previously untreated locally recurrent, unresectable, or metastatic triple-negative breast cancer.

Progression-free survival (PFS) was 10.8 months in the Datroway group, reducing the risk of disease progression or death by 43% compared to the chemotherapy group (5.6 months) (HR 0.57, p<0.0001). Overall survival (OS) was 23.7 months, extending by 5 months compared to the control group (18.7 months) (HR 0.79, p=0.0291).

Furthermore, the objective response rate (ORR) was 62.5% in the Datroway group and 29.3% in the chemotherapy group, showing more than double the difference.

Triple-negative breast cancer inherently remains an aggressive subtype with no actionable targets. When immunotherapy is not an option, the median overall survival (OS) is known to be around 12-13 months, making the study results particularly positive.

The findings are expected to fill a significant treatment gap, especially by offering a practical alternative for patients ineligible for immunotherapy.

Professor Jung stated, “The core finding of this study is the statistically significant improvement not only in progression-free survival but also in overall survival. This is not just a simple number but a change that alters the actual survival curve for patients.”

She further conveyed, “This demonstrates that we have moved beyond the era of relying solely on cytotoxic chemotherapy, showing that survival extension is now possible even in the non-immunotherapy group.”

This study is also notable for including patients with poor prognoses. It encompassed not only those ineligible for immunotherapy due to PD-L1 negativity or underlying conditions, but also patients who relapsed after immunotherapy and high-risk patients who relapsed within 6 months post-surgery.

Professor Jung remarked, “While most studies exclude such patients, this research reflects real-world clinical practice. It is exceptional that overall survival was extended by approximately 2 years even in this poor-prognosis patient group.”

She further explained, “The objective response rate exceeded 60%, and a high proportion of patients experienced rapid tumor shrinkage. Since triple-negative breast cancer often progresses rapidly, with patients experiencing significant tumor growth, these results could directly impact patient quality of life. The prolonged duration of response observed in this clinical trial demonstrates that not only the response rate but also the sustained responses can translate into survival.”

Filling the gap in HER2-negative and PD-L1-low expression... “New challenge in treatment sequencing strategy”

Professor Jung also projected that its use will vary depending on how the indication is approved domestically and which treatment receives insurance reimbursement first.

Analysis suggests it could become the sole treatment for patients with early-relapsed TNBC, pending approval by the Ministry of Food and Drug Safety (MFDS).

She stated, “The MFDS often approves treatments by directly adopting the clinical trial subject criteria as the approved indications. Therefore, if patients relapsing within 6 months are included in the approved scope, Datroway could effectively become the only treatment option for patients with early-relapsed TNBC.”

Professor Jung highlighted the need for future sequence studies focusing on HER2-low and PD-L1-low patient populations.

She projected, “While Enhertu (trastuzumab deruxtecan) could be considered for HER2-low patients, its prevalence in triple-negative breast cancer is low, and the similar payload structures of the two drugs could reduce efficacy when used sequentially. Clinical strategy regarding the sequence of drug administration in these patient groups will become increasingly important.”

The mechanism-based characteristics of TROP2-targeted therapies also warrant attention.

Professor Jung stated, “While most triple-negative breast cancer patients express TROP2, the efficacy was consistently demonstrated regardless of the expression level. Therefore, therapeutic benefits can be expected without the need for separate biomarker testing.”

She assessed, “These results provide significant data that point the way for future development of TROP2-targeted antibody-drug conjugates.”

Ultimately, the biggest practical hurdle to realizing therapeutic benefits is reimbursement coverage. Professor Jung emphasized that overcoming this accessibility barrier is crucial moving forward.

Professor Jung added, “Even a good drug remains inaccessible to patients without insurance coverage. Compared to existing cytotoxic anticancer drugs, new drugs inevitably carry higher prices, making reimbursement challenging from a cost-effectiveness perspective. Ultimately, drug pricing and reimbursement policies are decisive factors for access.”