Table 1.
Novel drugs for treating different molecular subtypes of breast cancer (BC).
| Drug (alternative names) | Mode of action | Targeted population | Monotherapy or combination therapy | Latest stage of clinical development |
|---|---|---|---|---|
| I. For treating HR+ BC | ||||
| Palbociclib (Ibrance®) | Oral small-molecule inhibitor of cyclin-dependent kinase CDK4 and CDK6 | Advanced stage, HER2− | Combination therapy with letrozole | Approved by US FDA (February 2015) |
| Advanced stage, pretreated, HER2− | Combination therapy with fulvestrant | Phase III | ||
| Ribociclib (Kisqali®) | Oral small-molecule inhibitor of CDK4 and CDK6 | Advanced stage, HER2− | Combination therapy with letrozole | Approved by US FDA (March 2017) |
| Advanced stage, pretreated, HER2− | Combination therapy with fulvestrant | Phase III (ongoing) | ||
| Abemaciclib (LY2835219) | Oral small-molecule inhibitor of CDK4 and CDK6 | Advanced stage, HER2− | Combination therapy with letrozole | Phase III (ongoing) |
| Advanced stage, pretreated, HER2− | Combination therapy with fulvestrant | Phase III | ||
| Buparlisb (BKM120) | Oral small-molecule inhibitor of pan-class I phosphatidylinositol 3-kinase (PI3K) | Advanced stage, pretreated, HER2− | Combination therapy with fulvestrant | Phase III |
| Early stage, HER2− | Combination therapy with letrozole | Phase II (ongoing) | ||
| Pictilisib (GDC-0941) | Oral small-molecule inhibitor of pan-class I PI3K | Advanced stage, pretreated, HER2− | Combination therapy with fulvestrant | Phase II (will not be further pursued) |
| Early stage, HER2− | Combination therapy with anaestrozole | Phase II | ||
| Pilaralisib (SAR245408) | Oral small-molecule inhibitor of pan-class I PI3K | Advanced stage, pretreated, HER2− | Combination therapy with letrozole | Phase I/II (will not be further pursued) |
| Voxtalisib (SAR245409) | Oral small-molecule inhibitor of pan-class I PI3K and mammalian target of rapamycin (mTOR) | Advanced stage, pretreated, HER2− | Combination therapy with letrozole | Phase I/II (will not be further pursued) |
| Alpeisib (BYL719) | Oral small-molecule inhibitor of α-specific class I PI3K | Advanced stage, pretreated, HER2− | Combination therapy with fulvestrant | Phase III (ongoing) |
| Early stage, HER2− | Combination therapy with letrozole | Phase II (ongoing) | ||
| Taselisib (GDC-0032) | Oral small-molecule inhibitor of α-specific class I PI3K | Advanced stage, pretreated, HER2− | Combination therapy with fulvestrant | Phase II (ongoing) |
| Everolimus (Afintor®) | Oral small-molecule inhibitor of mTOR | Advanced stage, pretreated | Combination therapy with exemestane | Approved by US FDA (July 2012) |
| Temsirolimus (Torisel®) | Oral small-molecule inhibitor of mTOR | Advanced stage | Combination therapy with letrozole | Phase III |
| Advanced stage, pretreated | Monotherapy | Phase II (will not be further pursued) | ||
| Entinostat | Histone deacetylase (HDAC) inhibitor | Advanced stage, pretreated | Combination therapy with exemestane | Phase III (ongoing) |
| Vorinostat | HDAC inhibitor | Advanced stage, pretreated | Combination therapy with tamoxifen | Phase II |
| II. For treating HER2+ BC | ||||
| Buparlisb (BKM120) | Oral small-molecule inhibitor of pan-class I PI3K | Advanced stage, pretreated | Combination therapy with lapatinib | Phase Ib |
| Advanced stage, pretreated | Combination therapy with trastuzumab and paclitaxel | Phase II | ||
| Pilaralisib (SAR245408) | Oral small-molecule inhibitor of pan-class I PI3K | Advanced stage, pretreated | Combination therapy with trastuzumab/trastuzumab and paclitaxel | Phase I/II |
| MK-2206 | Oral small-molecule inhibitor of protein kinase B | Advanced stage, pretreated | Combination therapy with trastuzumab | Phase I |
| Everolimus (Afintor®) | Oral small-molecule inhibitor of mTOR | Advanced stage, pretreated | Combination therapy with trastuzumab and vinorelbine | Phase III |
| Ridaforolimus (MK-8669) | Oral small-molecule inhibitor of mTOR | Advanced stage, pretreated | Combination therapy with trastuzumab | Phase IIb |
| Sirolimus | Oral small-molecule inhibitor of mTOR | Advanced stage, pretreated | Combination therapy with trastuzumab | Phase II |
| Neratinib (HKI-272) | Irreversible binder of HER1, HER2, and HER4 | Early stage, pretreated | Monotherapy | Phase III |
| Patritumab (AMG 888, U3-1287) | Anti-HER3 monoclonal antibody | Advanced stage | Combination therapy with trastuzumab and paclitaxel | Phase Ib |
| Margetuximab (MGAH22) | Anti-HER2 monoclonal antibody | Advanced stage | Monotherapy | Phase I |
| Lonafarnib (SCH66336) | Farnesyl transferase inhibitor | Advanced stage | Combination therapy with trastuzumab and paclitaxel | Phase I |
| Nelipepimut-S (E75) | Therapeutic peptide vaccine | Early stage | Combination therapy with trastuzumab | Phase II (ongoing) |
| Recombinant HER2 protein (dHER2) | Therapeutic peptide vaccine | Early stage | Monotherapy | Phase I |
| Advanced stage | Monotherapy | Phase I/II | ||
| Advanced stage, pretreated | Combination therapy with lapatinib | Phase I | ||
| III. For treating triple negative breast cancer | ||||
| Olaparib (Lynparza®) | Oral PARP inhibitor | Advanced stage, HER2−, gBRCA+ | Monotherapy | Phase III |
| Talazoparib (BMN 673) | Oral PARP inhibitor | Advanced stage, HER2−, gBRCA+ | Monotherapy | Phase III (ongoing) |
| Veliparib (ABT-888) | Oral PARP inhibitor | Advanced stage, HER2−, gBRCA+ | Combination therapy with carboplatin and paclitaxel | Phase III (ongoing) |
| Niraparib (Zejula®) | Oral PARP inhibitor | Advanced stage, HER2−, gBRCA+ | Monotherapy | Phase III (ongoing) |
| Combination therapy with pembrolizumab | Phase I/II (ongoing) | |||
| Rucaparib (Rubraca®) | Oral PARP inhibitor | Advanced stage, HER2−, gBRCA+ | Monotherapy | Phase II (ongoing) |
| Combination therapy with cisplatin | Phase II (ongoing) | |||
| Glembatumumab vedotin | Antibody-drug conjugate | Advanced stage, pretreated, gpNMB+ | Monotherapy | Phase II (ongoing) |
| Bicalutamide (Casodex®) | Androgen-receptor inhibitor | Advanced stage, AR+, HR− | Monotherapy | Phase II |
| Pembrolizumab (Keytruda®) | Anti-PD-1 monoclonal antibody | Advanced stage | Monotherapy | Phase II (ongoing) |