Table 2.
Antibody–drug conjugates in the treatment of ER+ breast cancer
| Drug | Target and payload | Current data | Ongoing phase III trials in ER + advanced breast cancer |
|---|---|---|---|
| Trastuzumab deruxtecan (DS-8201a,T-DXd Daiichi Sankyo, Astra Zeneca) | HER2/topoisomerase I inhibitor (DXd) |
Destiny-Breast 04 (n = 373) T-DXd versus TPC, 1-2 prior chemo, HER 2 1+/2+ ER+ cohort (n = 331) mPFS: 10.1 versus 5.4 months (HR 0.51; 95% CI: 0.40-0.64, P < 0.001) mOS: 23.9 versus 17.5 months (HR 0.64; 95% CI: 0.48-0.86, P = 0.003) |
Destiny-Breast 06 (n = 850) – NCT04494425: trastuzumab deruxtecan versus investigator’s choice chemotherapy; no prior chemotherapy for MBC; HER2 + or ++ or >0<1 |
| Datopotamab deruxtecan (Dato-DXd, Daiichi Sankyo, AstraZeneca) | Trop2/topoisomerase I inhibitor (DXd) | NA in ER+ MBC | Tropion-Breast01 (n = 700) – NCT 0510486: A phase III, 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 |
| Sacituzumab govitecan (SG, Trodelvy®, Immunomedics) | Trop-2/topoisomerase I inhibitor (SN-38) |
Tropics-2 (n = 543) SG versus TPC, 2-4 prior chemo mPFS: 5.5 versus 4.0 months (HR 0.66; 95% CI: 0.53-0.83, P = 0.0001) mOS: 24.4 versus 11.2 months (HR 0.79; 95% CI: 0.65-0.96, P = 0.02) |
None |
| Patritumab deruxtecan (HER3-DXd, U3-1402, Daiichi Sankyo) | HER3 (patritumumab)/topoisomerase I inhibitor (DXd) | HER3+/ER+/HER2− MBC n = 113 Prior regimens: 6 (2-13) RR: 30.1%, mPFS: 7.4 months 6 months PFS: 53.5% |
None |
CI, confidence interval; ER, estrogen receptor; HER2, Human epidermal growth factor 2; HR, hazard ratio; MBC, NA, not available; OS, overall survival; PFS, progression-free survival; SG, sacituzumab govitecan; TPC, treatment of physician’s choice.