Datopotamab Deruxtecan Improves Survival Outcomes in Advanced Triple-Negative Breast Cancer

Datopotamab deruxtecan (Datroway) demonstrated improved progression-free survival (PFS) and overall survival (OS) compared with standard chemotherapy in patients with previously untreated, advanced triple-negative breast cancer (TNBC) who were not eligible for immunotherapy, according to results from the phase 3 TROPION-Breast02 trial.

The findings, published in Annals of Oncology, address a significant unmet need in TNBC, particularly among the approximately 70% of patients who are not candidates for immunotherapy due to low PD-L1 expression or other clinical factors.

Efficacy Outcomes

The study met its primary end points, showing clinically meaningful improvements across multiple efficacy measures.

Median PFS was 10.8 months in the datopotamab deruxtecan arm compared with 5.6 months in the chemotherapy arm, representing an improvement of more than 5 months.

Median OS was 23.7 months versus 18.7 months, respectively, demonstrating a 5-month survival benefit.

The confirmed objective response rate (ORR) was 63% with datopotamab deruxtecan compared with 29% with chemotherapy. Complete responses were observed in 9% of patients receiving datopotamab deruxtecan versus 2% in the chemotherapy group.

Among responders, the median duration of response was 12.3 months in the experimental arm compared with 7.1 months in the chemotherapy arm.

Trial Design and Patient Population

TROPION-Breast02 was an international, randomized, open-label phase 3 trial conducted between May 2022 and June 2024 across 229 centers in 23 countries.

The trial enrolled 644 patients with locally recurrent inoperable or metastatic TNBC who had not received prior systemic therapy for advanced disease. Patients were randomly assigned to receive datopotamab deruxtecan (n = 323) or investigator’s choice of chemotherapy (n = 321), including nab-paclitaxel, paclitaxel, eribulin, carboplatin or capecitabine.

Notably, the study included patients often excluded from clinical trials, such as those with brain metastases and those with early relapse following prior treatment, enhancing the generalizability of the findings.

Datopotamab deruxtecan is a TROP2-directed antibody-drug conjugate that delivers a cytotoxic payload directly to tumor cells, allowing for targeted cell death while limiting systemic exposure.

Safety and Adverse Event Profile

The safety profile of datopotamab deruxtecan was consistent with prior studies. Patients in the experimental arm had a longer median treatment duration (8.5 months) compared with those receiving chemotherapy (4.1 months).

Treatment-related adverse events (TRAEs) occurred in 93% of patients receiving datopotamab deruxtecan and 83% of those receiving chemotherapy. Grade 3 or higher TRAEs were reported in 33% and 29% of patients, respectively.

Treatment discontinuation due to adverse events occurred less frequently in the datopotamab deruxtecan arm (4%) compared with chemotherapy (7%). No treatment-related deaths were reported in either group.

The most common adverse events associated with datopotamab deruxtecan included:

• Stomatitis (57%)
• Nausea (45%)
• Alopecia (41%)
• Fatigue (32%)
• Dry eye (24%)

In contrast, chemotherapy-related adverse events most commonly included:

• Alopecia (31%)
• Neutropenia (29%)
• Fatigue (28%)

Adverse events of special interest with datopotamab deruxtecan included ocular toxicities, primarily mild dry eye, and interstitial lung disease (ILD)/pneumonitis, which occurred in 3% of patients. Most ILD events were low grade; however, one treatment-related fatal event was reported.

Nursing Considerations

Oncology nurses play a critical role in early identification and management of toxicities associated with antibody-drug conjugates.

Patients receiving datopotamab deruxtecan should be monitored for:

• Oral mucositis, with proactive oral care interventions
• Ocular symptoms, including dryness or irritation, with early ophthalmologic referral as needed
• Respiratory symptoms suggestive of ILD, including cough or dyspnea, requiring prompt evaluation

Patient education is essential to ensure early reporting of symptoms, particularly given the potential severity of ILD.

Importantly, patient-reported outcomes indicated improvements in pain and physical functioning with datopotamab deruxtecan compared with chemotherapy, which may influence quality-of-life discussions and shared decision-making.

Clinical Implications

These findings support datopotamab deruxtecan as a potential first-line treatment option for patients with advanced TNBC who are not eligible for immunotherapy. The improved survival outcomes, manageable safety profile and patient-reported benefits highlight its emerging role in this setting.

Reference

1. Dent RA, et al. Datopotamab deruxtecan in patients with untreated, advanced triple-negative breast cancer (TROPION-Breast02): a randomized, open-label, international, phase 3 trial. Ann Oncol.