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. 2021 Jan 20;13(3):369. doi: 10.3390/cancers13030369

Table 2.

Combination therapies for anti-estrogen resistant breast cancers.

Current Strategies FDA Approved Drugs/Drug Combinations and Associated Clinical Trials Drugs/Drug Combinations in Clinical Trials
Target mutant ERα through new class of SERDs Fulvestrant [75] AZD9496, GDC0927, RAD1901, GDC0810 [76,77]
Inhibition of CCND1-CDK4/6-RB pathway

  1. Palbociclib and Letrozole combination (PALOMA-2 trial) [78,79]

  2. Palbociclib and Fulvestrant Combination (PALOMA-3 trial) [80,81]

  3. Abemaciclib as monotherapy (MONARCH-1 trial) [82]

  4. Abemaciclib in combination with Fulvestrant (MONARCH-2 trial) [83]

  5. Abemaciclib combined with non-steroidal aromatase inhibitors letrozole or amastrozole (MONARCH-3 trial) [84]

 Ribociclib (LEE011) in combination with endocrine therapy (Tamoxifen and Goserelin or a nonsteroidal aromatase inhibitor and Goserelin) (MONALEESA-7 trial) [85]
Inhibition of the PI3K-AKT-mTOR pathway

  1. Alpelisib and Fulvestrant combination (SOLAR-1 trial) [86]

  2. Everolimus in combination with Exemestane (BOLERO-2 trial) [87,88]

 Ipatasertib in combination with endocrine therapy and a CDK4/6 inhibitor (TAKTIC trial) [89]
Concurrent inhibition of ERα, CCND1-CDK4/6-RB pathway and the PI3K-AKT-mTOR pathways Triplet therapy combining Palbociclib, Taselisib and Fulvestrant and doublet therapy combining Palbociclib and Taselisib [90]