FDA Approves Datopotamab Deruxtecan for Advanced Breast Cancer
Datopotamab deruxtecan-dlnk received approval from the FDA for previously treated unresectable or metastatic, HR-positive, HER2-negative breast cancer.
FDA approves Dato-DXd for certain HR-positive, HER2-negative metastatic breast cancers.
The FDA granted approval to datopotamab deruxtecan-dlnk (Dato-DXd; Datroway) for the treatment of adult patients with unresectable or metastatic, HR-positive, HER2-negative breast cancer previously treated with endocrine-based therapy and chemotherapy.1
This approval was based on findings from the TROPION-Breast01 trial (NCT05104866), according to an alert from the FDA. In this multicenter, open-label, randomized trial, 732 patients with previously treated unresectable or metastatic, HR-positive, HER2-negative breast cancer were randomized 1:1 to receive either Dato-DXd (n = 365) or investigator’s choice of chemotherapy (n = 367), which included capecitabine (21%), eribulin (60%), gemcitabine (9%), and vinorelbine (10%).
The major efficacy outcome measures in this trial were overall survival (OS) and progression-free survival (PFS), assessed by blinded independent central review (BICR), based on RECIST v1.1.
Patients treated with Dato-DXd had a median PFS of 6.9 months (95% CI, 5.7-7.4) compared with 4.9 months (95% CI, 4.2-5.5) in those treated with chemotherapy (HR = 0.63; 95% CI, 0.52-0.76; two-sided P < .0001). Additionally, the median OS was 18.6 months (95% CI, 17.3-20.1) in the Dato-DXd group vs 18.3 months (95% CI, 17.3-20.5) in the chemotherapy group (HR = 1.01; 95% CI, 0.83-1.22), which did not have a statistically significant two-sided P value, according to the FDA’s alert.
The Dato-DXd and chemotherapy groups had a confirmed objective response rate of 36% (95% CI, 31%-42%) and 23% (95% CI, 19%-28%), respectively, and a median duration of response of 6.7 months (95% CI, 5.6-9.8) and 5.7 months (95% CI, 4.9-6.8), as noted in the alert.
The most common adverse reactions, occurring in at least 20% of patients, included nausea, stomatitis, decreased leukocyte levels, fatigue, alopecia, decreased calcium levels, decreased hemoglobin levels, decreased lymphocyte levels, constipation, dry eye, decreased neutrophil levels, vomiting, increased AST levels, keratitis, increased ALT levels, and increased alkaline phosphatase levels.
According to the FDA, the recommended dose is 6 mg/kg, with a maximum of 540 mg for patients 90 kg and greater, to be administered via intravenous infusion, once every 3 weeks as part of a 21-day cycle. Treatment is recommended until unacceptable toxicity or disease progression.
Additional Findings from the TROPION-Breast01 Trial
Data from this trial were presented at the ESMO Congress 2023, which demonstrated that after a median follow-up of 10.8 months, 93 patients in the Dato-DXd arm and 39 in the chemotherapy arm were still ongoing with study treatment.2 In both arms, patients discontinued treatment as a result of progressive disease (267 vs 240), adverse events (11 vs 10), patient decision (13 vs 32), death (2 vs 7), or other (12 vs 23).
“As of data cutoff, approximately 3 times the number of patients are still on Dato-DXd, as compared to the standard chemotherapy arm,” Aditya Bardia, MD, MPH, director of breast cancer research and medical oncology, Massachusetts General Hospital Cancer Center, and associate professor at Harvard Medical School, Boston, said during a presentation of the data. “[The] majority of patients who discontinued the study had disease progression.”
Treatment-related adverse events (TRAEs) occurred in 94% and 86% of the Dato-DXd and ICC groups; however, the rate of grade 3 or higher TRAEs was less than half with the TROP2-directed antibody-drug conjugate (ADC) vs ICC (21% vs 45%, respectively).
TRAEs led to dose reductions in 21% of the Dato-DXd arm, compared with 30% in the ICC arm, dose interruptions in 12% and 25%, respectively, and treatment discontinuation in 3% of each arm. One patient death occurred in the ICC group. Serious TRAEs occurred in 6% of the Dato-DXd arm and 9% of the ICC arm.
Trial Design
In the TROPION-Breast01 trial, researchers evaluated the efficacy of Dato-DXd in patients whose disease progressed, were considered unsuitable for further endocrine therapy, and received 1 or 2 lines of prior chemotherapy for the treatment of unresectable or metastatic disease.1 Of note, exclusion criteria included a history of interstitial lung disease (ILD)/pneumonitis requiring steroids, clinically active brain metastases, ongoing ILD/pneumonitis, clinically significant corneal disease, and an ECOG performance status greater than 1.
For randomization, patients were stratified by prior CDK4/6 inhibitor treatment, previous lines of chemotherapy, and geographical region.
References
- FDA approves datopotamab deruxtecan-dlnk for unresectable or metastatic, HR-positive, HER2-negative breast cancer. FDA. January 17, 2024. Accessed January 17, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-datopotamab-deruxtecan-dlnk-unresectable-or-metastatic-hr-positive-her2-negative-breast
- Bardia A, Jhaveri K, Im SA, et al. Datopotamab deruxtecan (Dato-DXd) vs chemotherapy in previously-treated inoperable or metastatic hormone receptor-positive, HER2-negative (HR+/HER2–) breast cancer: Primary results from the randomized phase 3 TROPION-Breast01 trial. Presented at: ESMO Congress 2023; October 20-24, 2023; Madrid, Spain. Abstract LBA 11.
Sotorasib Plus Panitumumab Receives FDA Approval for KRAS G12C–Mutated Colorectal Cancer
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