DESTINY-Breast03 Phase 3 Study Results
HER2-low mBC: Unmet Clinical Need
DESTINY-Breast04
10
Daiichi-Sankyo
Current Standard of Care
HER2-negative
(IHC 0, IHC 1+, IHC 2+/ISH-)
HR+a
Endocrine therapy (ET)
ET combinations
PARP inhibitors (gBRCA+)
HER2-low
HR-b
Checkpoint inhibitors (PD-L1+)
PARP inhibitors (gBRCA+)
Sacituzumab govitecan
Chemotherapy
ASCO 2022 #LBA3 Plenary Session
HER2-low mBC is defined by IHC scores of 1+ or 2+/ISH-
-
This is a heterogenous population with a high prevalence of HR
coexpression and without a distinct biology
HER2-low mBC is treated as HER2- mBC, with limited options
for later lines of therapy 1-4
Current HER2-targeted therapies are not effective for patients with
tumors that express lower levels of HER2
Therapeutic options for patients with HR+/HER2- mBC after
CDK4/6i progression have limited efficacy
Real-world studies suggest a PFS of <4 months after progressive
disease with CDK4/6i5
Limited benefit exists for patients who progress after multiple
lines of chemotherapy
In a pooled analysis of patients with HER2- mBC, eribulin and
capecitabine provide minimal benefit, with a mPFS of ~4 months and
MOS of ~15 months6
CDK4/6i, cyclin-dependent kinase 4/6 inhibitors; gBRCA+, germline breast cancer gene positive; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; IHC, immunohistochemistry; ISH, in
situ hybridization; mBC, metastatic breast cancer; mOS, median overall survival; PARP, poly (ADP-ribose) polymerase; PD-L1, programmed death ligand 1; mPFS, median progression-free survival; T-DXd,
trastuzumab deruxtecan.
aImmunoreactive for estrogen or progesterone receptor in ≥1% tumor cell nuclei. "Immunoreactive for estrogen or progesterone receptor in <1% tumor cell nuclei.
1. Tarantino P, et al. J Clin Oncol. 2020;38(17):1951-1962. 2. Aogi K, et al. Ann Oncol. 2012;23:1441-1448. 3. Eiger D, et al. Cancers (Basel). 2021;13(5):1015. 4. Fehrenbacher L, et al. J Clin Oncol.
2019;38(5):444-453. 5. Mo H, et al. Clin Breast Cancer. 2022;22:143-148. 6. Kaufman PA, et al. J Clin Oncol. 2015;33:594-601.
5View entire presentation