On January 17, 2025, the Food and Drug Administration sanctioned datopotamab deruxtecan-dlnk (Datroway, Daiichi Sankyo, Inc.), a Trop-2-targeted antibody and topoisomerase inhibitor conjugate, for adult patients with unresectable or metastatic, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+, or IHC 2+/ISH-) breast cancer who have previously undergone endocrine-based therapy and chemotherapy for unresectable or metastatic disease.
Effectiveness and Safety
The efficacy was assessed in TROPION-Breast01 (NCT05104866), a multicenter, open-label, randomized study. Patients must have undergone disease progression, been considered inappropriate for additional endocrine therapy, and received one or two prior lines of chemotherapy for unresectable or metastatic illness. Patients were eliminated due to a history of interstitial lung disease/pneumonitis necessitating steroids, active interstitial lung disease/pneumonitis, clinically active brain metastases, or substantial corneal disease. Patients were also excluded for an ECOG performance status greater than 1.
Randomization was stratified according to past lines of chemotherapy, previous treatment with CDK4/6 inhibitors, and geographical area. A total of 732 patients were randomized in a 1:1 ratio to receive either datopotamab deruxtecan-dlnk (n=365) or the investigator’s choice of chemotherapy (n=367), which included eribulin (60%), capecitabine (21%), vinorelbine (10%), or gemcitabine (9%).
The primary efficacy outcome measures were progression-free survival (PFS), evaluated by blinded independent central review (BICR) according to RECIST v1.1, and overall survival (OS). Supplementary efficacy outcomes encompassed the confirmed objective response rate (ORR) and the duration of response (DOR) as assessed by BICR. The median progression-free survival (PFS) was 6.9 months (95% CI: 5.7, 7.4) for the datopotamab deruxtecan-dlnk group and 4.9 months (95% CI: 4.2, 5.5) for the chemotherapy group, with a hazard ratio of 0.63 (95% CI: 0.52, 0.76) and a two-sided p-value of less than 0.0001.
The median overall survival (OS) was 18.6 months (95% CI: 17.3, 20.1) for the datopotamab deruxtecan-dlnk group and 18.3 months (95% CI: 17.3, 20.5) for the chemotherapy group, with a hazard ratio of 1.01 (95% CI: 0.83, 1.22); the two-sided p-value was not statistically significant.
The confirmed overall response rate (ORR) was 36% (95% CI: 31, 42) and 23% (95% CI: 19, 28), while the median duration of response (DOR) was 6.7 months (95% CI: 5.6, 9.8) and 5.7 months (95% CI: 4.9, 6.8) in the datopotamab deruxtecan-dlnk and chemotherapy groups, respectively.
The predominant adverse reactions (≥20%), encompassing laboratory abnormalities, included stomatitis, nausea, fatigue, leukopenia, hypocalcemia, alopecia, lymphopenia, anemia, constipation, neutropenia, dry eye, vomiting, elevated ALT, keratitis, elevated AST, and increased alkaline phosphatase levels.
The advised dosage of datopotamab deruxtecan-dlnk is 6 mg/kg (with a maximum of 540 mg for patients weighing ≥90 kg), delivered via intravenous infusion once every three weeks (21-day cycle), unless disease progression or intolerable toxicity occurs.
Dr. Nishant Mittal is a highly accomplished researcher with over 13 years of experience in the fields of cardiovascular biology and cancer research. His career is marked by significant contributions to stem cell biology, developmental biology, and innovative research techniques.
Research Highlights
Dr. Mittal's research has focused on several key areas:
1) Cardiovascular Development and Regeneration: He studied coronary vessel development and regeneration using zebrafish models1.
2) Cancer Biology: At Dartmouth College, he developed zebrafish models for studying tumor heterogeneity and clonal evolution in pancreatic cancer.
3) Developmental Biology: His doctoral work at Keio University involved identifying and characterizing medaka fish mutants with cardiovascular defects.
4) Stem Cell Research: He investigated the effects of folic acid on mouse embryonic stem cells and worked on cryopreservation techniques for hematopoietic stem cells.
Publications and Presentations
Dr. Mittal has authored several peer-reviewed publications in reputable journals such as Scientific Reports, Cardiovascular Research, and Disease Models & Mechanisms1. He has also presented his research at numerous international conferences, including the Stanford-Weill Cornell Cardiovascular Research Symposium and the Weinstein Cardiovascular Development Conference.
In summary, Dr. Nishant Mittal is a dedicated and accomplished researcher with a strong track record in cardiovascular and cancer biology, demonstrating expertise in various model systems and a commitment to advancing scientific knowledge through innovative research approaches.
