Table 2.
Select drugs approved and indicated to treat metastatic breast cancer as mono or combination therapies in the past 5 years (2015–2020).*
| Common (Brand) name | MBC drug target (phenotype) | Drug platform Small or biologic molecules | Combination or mono-drugtherapy | Route | Pharmacological mechanisms | Efficacy (Primary outcome measure) | Main side effects | Ref |
|---|---|---|---|---|---|---|---|---|
| Approved in 2020 | ||||||||
| Margetuximab (Margenza) | HER2 (HER2+) | Monoclonal antibody (Biologics) | In combination with capecitabine, eribulin, gemcitabine, or vinorelbine | IV | An Fc-engineered chimeric anti-ERBB2 immunoglobulin G1 that has increased activation of antibody-dependent cellular cytotoxicity and natural killer cells, relative to trastuzumab. | Median PFS in the margetuximab group was 5.8 months vs 4.9 months in the control group | Infusion-related reactions, left ventricular dysfunction | (Rugo, et al., 2021) |
| Sacituzumab-govitecan (Trodelvy**) | Trop-2, topoisomerase-I (TNBC) | Antibody-drug conjugate (Biologic) | Mono-drug therapy | IV | This drug contains SN-38. The mAb delivers SN-38 into Trop-2+ TNBC cells. SN-38 is topoisomerase-I inhibitor. | Median PFS in sacituzumab govitecan group was 4.8 months vs 1.7 months in chemotherapy group | Neutropenia, hypersensitivity | (Bardia, et al., 2021) |
| Tucatinib (Tukysa) | HER2&3 kinase (HER2+) | Small Molecule | In combination with trastuzumab and capecitabine | PO | Tucatinib inhibits phosphorylation of HER2 and HER3, resulting in inhibition of downstream MAPK and AKT signaling and cell proliferation | Median PFS in tucatinib combination group was 7.8 months vs 5.6 months in placebo combination group | Elevated aminotransferase levels | (Murthy, et al., 2020) |
| Approved in 2019 | ||||||||
| Trastuzumab-deruxtecan (Enhertu) | HER2, Topoisomerase-I (HER2+) | Antibody-drug conjugate (Biologic) | Mono-drug therapy | IV | Trastuzumab-deruxtecan targets HER-2+ MBC. Deruxtecan(Dxd) is a topoisomerase I inhibitor. | The median response duration was 14.8 months and the median PFS was 16.4 months | Neutrophil count decreases | (Modi, et al., 2020) |
| Alpelisib (Piqray) | PI3K (HR+) | Small Molecule | In combination with fulvestrant | PO | Alpelisib selectively inhibits PI3K in the PI3K/AKT kinase signaling pathway, which results in inhibition of tumor cell proliferation. | Median PFS was 11.0 months in the alpelisib plus fulvestrant group vs 5.7 months in the placebo plus fulvestrant group | Hyperglycemia | (Andre, et al., 2019) |
| Approved in 2018 | ||||||||
| Talazoparib (Talzenna) | PARP (BRCA, HER2−) | Small Molecule | In combination with capecitabine, eribulin, gemcitabine, or vinorelbine | PO | Talazoparib binds to and inhibits PARP enzymatic activity, then increases formation of PARP-DNA complexes resulting in DNA damage in tumor cells. | Median PFS was 8.6 months in talazoparib group vs 5.6 months in the standard therapy group | Anemia, thrombocytopenia | (Litton, et al., 2018) |
| Approved in 2017 | ||||||||
| Abemaciclib (Verzenio) | CDK4/6 (HR+, HER2−) | Small Molecule | In combination with fulvestrant | PO | Abemaciclib inhibits CDK4 and CDK6, thus, it inhibits retinoblastoma protein phosphorylation in G1 phase resulting in arresting the cell cycle in the G1 phase | Median PFS was 16.4 in abemaciclib plus fulvestrant group vs 9.3 months in placebo group | Diarrhea, neutropenia | (George W. Sledge, et al., 2017) |
| Ribociclib (Kisqali) | CDK4/6 (HR+, HER2−) | Small Molecule | In combination with endocrine therapy, also received either as a nonsteroidal aromatase inhibitor or tamoxifen and goseline | PO | Ribociclib is an inhibitor of CDK 4 and 6 which interferes the phosphorylation of retinoblastoma protein and leads to arrest the cell cycle in the G1 phase. | Median PFS was 25.3 months in ribociclib plus letrozole group vs16.0 months in placebo plus letrozole group | Neutropenia, leucopenia | (Hortobagyi, et al., 2018) |
| Approved in 2015 | ||||||||
| Palbociclib (Ibrance) | CDK4/6 (HR+) | Small Molecule | In combination with letrozole | PO | Palbociclib is an inhibitor of CDK4 and CDK6 causing the prevention of Rb phosphorylation and E2F1 release, therefore leads to arrest the cell cycle in the G1 phase | Median PFS was 24.8 months in the palbociclib plus letrozole group vs 14.5 months in the placebo plus letrozole group | Neutropenia | (Finn, et al., 2016) |
*
Please see abbreviation list for the full names (PARP, CDK4/6, HR, HER2, E2F1, PFS).
**
Trodelvy received accelerated approval in April 2020 and regular approval in April 2021.