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Compared with chemotherapy, Dato-DXd demonstrates favorable median progression-free survival and overall survival in a phase 3 clinical trial.
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Updated January 17, 2025 at 2:30PM.
The FDA approved datopotamab deruxtecan-dlnk (Dato-DXd, Datroway; AstraZeneca, Daiichi Sankyo) for adult patients with unresectable or metastatic, hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) (IHC 0, IHC1+ or IHC2+/ISH-) breast cancer who have received prior endocrine-based therapy and chemotherapy.1 The treatment was evaluated in the phase 3 TROPION-Breast-01 (NCT05104866)2 clinical trial in which it demonstrated favorable progression-free survival (PFS) and overall survival (OS) when compared with chemotherapy.
Dato-DXd is a Trop-2-directed antibody and topoisomerase inhibitor conjugate that is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody. This attaches to topoisomerase 1 inhibitor payloads through tetrapeptide-based cleavable linkers. The treatment previously received a biologics license application in April 2024.3
In the open-label, randomized phase 3 TROPION-Breast01 clinical trial (NCT05104866), Dato-DXd was compared with investigator's choice of standard of care single-agent chemotherapy (eribulin, capecitabine, vinorelbine, or gemcitabine). The enrolled 732 participants had inoperable or metastatic HR+, HER- breast cancer who were previously treated with 1 or 2 lines of systemic therapy.1,2
According to the investigators, patients were randomly assigned by previous lines of chemotherapy, prior CDX4/6 inhibitor treatment, and geographical location. Patients were enrolled into one of the following arms: Dato-DXd, which was administered in 100-mg vials intravenously (IV; n = 365); or investigator’s choice of chemotherapy (n = 367), which was either, IV eribulin, oral capecitabine (21%), IV vinorelbine (10%), or IV gemcitabine (9%). The primary efficacy outcome measures included PFS and OS, and secondary outcomes included objective response rate (ORR), duration of response (DOR), disease control rate (DCR), among others.1,2
The findings demonstrated that, compared with chemotherapy, Dato-DXd had both favorable median PFS (6.9 months [95% CI: 5.7, 7.4] vs 4.9 months [95% CI: 4.2, 5.5]; HR 0.63 [95% CI: 0.52, 0.76] 2-sided p < .0001) compared with chemotherapy. Although Dato-DXd showed favorable OS, (18.6 months [95% CI: 17.3, 20.1] vs 18.3 months [95% CI: 17.3, 20.5]), it was not considered statistically significant in the current analysis (HR 1.01 [95% CI: 0.83, 1.22]; 2-sided p-value, not statistically significant)1 or in a previous analysis.4
Further, the confirmed ORRs were approximately 36% (95% CI: 31, 42) and 23% (95% CI: 19, 28) in the Dato-DXd and chemotherapy arms, respectively. Patients receiving Dato-DXd achieved a median DOR of about 6.7 months (95% CI: 5.6, 9.8) compared with 5.7 months (95% CI: 4.9, 6.8) in those receiving chemotherapy.1
Trial Name: A Phase-3, Open-Label, Randomized Study of Dato-DXd Versus Investigator's Choice of Chemotherapy (ICC) in Participants With Inoperable or Metastatic HR-Positive, HER2-Negative Breast Cancer Who Have Been Treated With One or Two Prior Lines of Systemic Chemotherapy (TROPION-Breast01)
ClinicalTrials.gov ID: NCT05104866
Sponsor: AstraZeneca
Completion Date (Estimated): August 15, 2025
According to the investigators, the most common adverse events (AEs), including laboratory abnormalities, consisted of the following: stomatitis; nausea; fatigue; decreased leukocytes, calcium, lymphocytes, hemoglobin, and neutrophils; alopecia; constipation; dry eye; vomiting; keratitis; and increased ALT, AST, and alkaline phosphatase.1
In a prior analysis3, treatment-related AEs that were grade 3 or higher occurred in approximately 21% and 45% of patients in the Dato-DXd and chemotherapy arms, respectively. These included stomatitis (6%; 3%), fatigue (2%; 2%) and anemia (1%; 2%).3 Similarly, a PFS analysis4 showed that the most common treatment-emergent AEs were any grade nausea (51.1%) and stomatitis (50%) in the Dato-DXd group, and neutropenia (42.5%) in the chemotherapy group. There were also occurrences of grade 3 or higher nausea (1.4%), stomatitis (6.4%), and neutropenia (30.8%) in these respective groups.4
