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The TROP2-directed antibody-drug conjugate Dato-DXd delayed progression compared with chemotherapy, but the final analysis did not show a statistically significant survival benefit. It is FDA-approved for previously treated, advanced hormone-receptor-positive, HER2-negative breast cancer.
Open-label phase 3 trial of 732 patients with hormone-receptor-positive, HER2-negative metastatic breast cancer after one or two lines of chemotherapy, randomised to datopotamab deruxtecan (Dato-DXd, 6 mg/kg) or investigator's choice chemotherapy (eribulin, vinorelbine, capecitabine or gemcitabine). Dual primary endpoints were PFS by blinded review and overall survival.
PFS was improved (6.9 vs 4.9 months, HR 0.63) with fewer high-grade adverse events, but the final overall survival analysis did not show a statistically significant improvement. The trial is a cautionary example that a TROP2 ADC can beat chemotherapy on PFS in an unselected population without establishing a survival advantage.
For unresectable or metastatic hormone-receptor-positive, HER2-negative breast cancer after endocrine-based therapy and chemotherapy for advanced disease, Dato-DXd is an FDA-approved option. TROPION-Breast01 showed longer progression-free survival and fewer severe treatment-related adverse events than chemotherapy; the final overall survival analysis did not show a statistically significant improvement. Approval in this setting does not establish a survival advantage or apply to postoperative early-stage disease.
Shares Binghe Xu, Aditya Bardia, TROPION-Breast01, Datopotamab deruxtecan.
Shares TROPION-Breast02, ADC sequencing, Datopotamab deruxtecan, Daiichi Sankyo.
Shares Seock-Ah Im, Binghe Xu, Payload-class switching as the rule for ADC sequencing, ADC sequencing.
Shares Carlos Barrios, Seock-Ah Im, Daiichi Sankyo, Progression-free survival (PFS).
Shares Seock-Ah Im, Binghe Xu, Payload-class switching as the rule for ADC sequencing, Daiichi Sankyo.
Shares TROPION-Breast02, ADC sequencing, Datopotamab deruxtecan, Daiichi Sankyo.
Shares Payload-class switching as the rule for ADC sequencing, ADC sequencing, Biomarkers are not validated or standardised, Topoisomerase-I inhibitors (and ADC payloads).
Shares TROP2 PET to choose and sequence TROP2 ADCs, Datopotamab deruxtecan, Daiichi Sankyo, Topoisomerase-I inhibitors (and ADC payloads).
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