Landmark Approval: DATROWAY Offers New Hope for Metastatic Hormone Receptor-Positive Breast Cancer Patients

The FDA has cleared DATROWAY (datopotamab deruxtecan-dlnk), a novel antibody-drug conjugate targeting TROP2, marking a significant advancement in treating patients with advanced HR-positive, HER2-negative breast cancer who have exhausted standard endocrine and chemotherapy options. This approval represents a critical development in addressing a disease where only approximately 30% of patients with metastatic involvement survive beyond five years.

Clinical Evidence Behind the Approval

The approval decision rests on compelling Phase III trial data from TROPION-Breast01, which demonstrated that DATROWAY reduces the risk of disease progression or death by 37% compared to conventional chemotherapy regimens (hazard ratio 0.63; 95% CI 0.52-0.76). The trial enrolled 732 patients across multiple continents, evaluating DATROWAY administered intravenously at 6mg/kg every three weeks against physician-selected single-agent chemotherapy options including eribulin, capecitabine, vinorelbine, or gemcitabine.

For patients receiving DATROWAY, median progression-free survival extended to 16.8 months versus 10.2 months with conventional chemotherapy, translating to a 2.8-month clinical benefit. The safety profile demonstrated manageable toxicity, with the most frequently occurring adverse effects being stomatitis (59%), nausea (56%), and fatigue (44%).

A Paradigm Shift in Treatment Approach

Dr. Aditya Bardia from UCLA’s Jonsson Comprehensive Cancer Center emphasized the clinical significance: “New therapies addressing disease progression following endocrine and chemotherapy exposure remain critically needed. The TROP2-directed mechanism of DATROWAY provides patients with an innovative treatment pathway beyond conventional cytotoxic chemotherapy.”

According to current epidemiology, HR-positive, HER2-negative tumors account for approximately 70% of newly diagnosed breast cancer cases in the United States, with annual incidence exceeding 300,000 cases. Following progression through endocrine-based therapies, patients face limited options with chemotherapy-associated poor response rates.

Expanding AstraZeneca’s Oncology Pipeline

This approval marks the eighth new medicine AstraZeneca has delivered from its commitment to introduce 20 novel therapies by 2030. Dave Fredrickson, Executive Vice President of AstraZeneca’s Oncology Hematology division, stated: “DATROWAY exemplifies our strategic focus on antibody-drug conjugates designed to improve upon and potentially replace conventional chemotherapy across multiple malignancies.”

The collaboration between AstraZeneca and Daiichi Sankyo, which has been jointly developing and commercializing DATROWAY since July 2020, continues to expand the therapeutic reach of TROP2-targeted approaches. Daiichi Sankyo maintains manufacturing and supply responsibilities and exclusive rights in Japan.

Broader Clinical Development Program

Beyond HR-positive breast cancer, DATROWAY is under investigation in more than 20 global trials targeting non-small cell lung cancer, triple-negative breast cancer, and other solid tumors. Seven additional Phase III trials in lung cancer and five in breast cancer are evaluating DATROWAY as monotherapy and in combination with complementary anticancer agents across various treatment settings.

Ken Keller, Global Head of Oncology at Daiichi Sankyo, noted: “This approval represents the fourth medicine from our oncology pipeline receiving US regulatory clearance, advancing our portfolio of innovative cancer treatments.”

Safety Considerations and Patient Selection

While DATROWAY demonstrates efficacy, careful patient monitoring remains essential. Serious adverse events requiring attention include interstitial lung disease/pneumonitis (1.1%), occurring in 0.3% of patients with fatal outcomes. Dose interruptions due to adverse reactions occurred in 22% of patients, most commonly for COVID-19 infection (3.3%), infusion-related reactions (1.4%), and stomatitis (1.9%). Approximately 3.1% of patients required permanent treatment discontinuation due to adverse effects, predominantly interstitial lung disease (1.7%) and fatigue (0.6%).

Dose reductions were necessary in 23% of patients, with stomatitis (13%), fatigue (3.1%), and nausea (2.5%) being the leading causes. Healthcare providers must implement appropriate monitoring strategies for keratin-related eye toxicity, renal function, and hematologic parameters.

Addressing an Unmet Clinical Need

Caitlin Lewis from Living Beyond Breast Cancer highlighted the significance: “The approval of DATROWAY addresses a critical gap in therapeutic options. For patients with HR-positive metastatic disease previously treated with endocrine and chemotherapy regimens, this represents a much-needed treatment advancement.”

The drug’s mechanism—utilizing a humanized anti-TROP2 monoclonal antibody conjugated to topoisomerase I inhibitor payloads through cleavable linkers—represents a sophisticated approach to targeted delivery of cytotoxic agents, potentially offering improved tolerability compared to non-selective chemotherapy.

Looking Forward

DATROWAY is now approved in both the United States and Japan for treating adult patients with unresectable or metastatic HR-positive, HER2-negative breast cancer who have progressed on prior endocrine-based therapy and chemotherapy. This regulatory milestone underscores the evolving landscape of breast cancer therapeutics and the potential for antibody-drug conjugates to redefine treatment standards across multiple malignancies.