FDA Approves Datroway as Targeted Chemotherapy for Metastatic Breast Cancer

The Food and Drug Administration (FDA) has approved Datroway (datopotamab deruxtecan), a new chemotherapy drug designed to treat adults with unresectable or metastatic hormone receptor (HR)-positive, HER2-negative breast cancer. This approval provides a new option for patients who have already undergone endocrine-based therapy and chemotherapy.

About 70% of individuals with breast cancer have HR-positive, HER2-negative breast cancer, making it the most common subtype of the disease. Datroway belongs to a promising new class of drugs called antibody-drug conjugates (ADCs). These treatments act like "guided missiles," delivering chemotherapy directly to cancer cells while minimizing harm to healthy tissue—an advantage over traditional chemotherapy.

"This approval gives us another tool in the arsenal for treating receptor-positive metastatic breast cancer, the most common metastatic subtype we encounter," said Dr. Natasha Hunter, a physician specializing in breast cancer at the Fred Hutch Cancer Center. "While I wouldn’t describe it as a game-changer, Datroway is definitely good news and provides an additional option for patients."

Clinical Trial Success

The FDA’s approval of Datroway is based on the results of a Phase 3 clinical trial that lasted 3.4 years and involved 3,533 participants. Patients were divided into two groups: one receiving Datroway and the other receiving standard chemotherapy treatments. Participants received treatment every three weeks.

The study found that patients on Datroway experienced approximately eight extra weeks of progression-free survival compared to those on standard chemotherapy. Additionally, Datroway demonstrated fewer severe side effects, with 21% of Datroway-treated participants experiencing adverse events compared to 45% in the standard chemotherapy group.

"Only one in three patients with metastatic HR-positive, HER2-negative breast cancer survive beyond five years after their diagnosis, highlighting the urgent need for more effective treatments," said Caitlin Lewis, Senior Vice President of Strategy & Mission at Living Beyond Breast Cancer. "Datroway offers hope and an important new option for these patients."

What Makes Datroway Unique?

Datroway is AstraZeneca and Daiichi Sankyo's second antibody-drug conjugate to receive FDA approval, following Enhertu (trastuzumab deruxtecan). Enhertu was approved for HER2-low or HER2-ultralow metastatic breast cancer, as well as certain forms of lung and gastric cancer. Unlike Enhertu, Datroway targets the TROP2 protein, which is found on the surface of many tumor cells.

Dr. Hunter explained that Datroway is essentially “an old chemotherapy drug tied to a modern antibody,” using advanced linkers to optimize delivery to cancer cells. It joins Trodelvy (sacituzumab govitecan), another TROP2-targeting ADC, though Trodelvy uses a different chemotherapy payload.

A major challenge with ADCs is determining the best sequence in which to use them for treatment. Hunter highlighted the difficulty of deciding how to integrate Datroway into treatment plans because there is little data comparing ADCs directly. When a patient stops responding to one ADC, it is not always clear whether resistance is due to the chemotherapy payload or the antibody itself.

Advantages and Concerns with ADCs

ADCs are transforming cancer care by reducing the toxic effects often associated with traditional chemotherapy. Unlike standard treatments that affect healthy tissue as well as cancer cells, ADCs deliver chemotherapy directly to tumors, minimizing damage to surrounding cells. However, this approach is not without risks.

The most common severe side effects associated with ADCs include lymphopenia and neutropenia, conditions that lower white blood cell counts and weaken immunity. A particular concern with Datroway is the risk of interstitial lung disease, a serious condition that causes lung scarring. AstraZeneca reported a 4.2% risk of Datroway-treated patients developing the condition.

Hunter emphasized that ADCs are initially tested in metastatic settings, but successful treatments are often moved into earlier stages of cancer therapy. “As ADCs continue to show promise in metastatic settings, they may gradually move forward in the treatment lineup. Over time, there’s potential for these therapies to become standard treatments for early-stage cancers.”

She added, “The difference between where we are today and where we will be in 20 to 30 years is really going to be remarkable. ADCs represent the future of cancer treatment."

With its advanced targeting capabilities and manageable side effect profile, Datroway is a valuable new option for patients facing metastatic breast cancer. While questions remain about its best use in treatment protocols, Datroway reinforces optimism about the growing role of ADCs in revolutionizing oncology care.