METHODS FOR TREATING CANCER
Disclosed herein are methods of treating one or more tumors by administering to the subject a therapeutically effective amount of a combination of RAD1901 or solvates (e.g., hydrate) or salts thereof and one or more second therapeutic agent(s) (e.g., everolimus). The cancer is an estrogen-dependent cancer, such as breast cancer, ovarian cancer, colon cancer, endometrial cancer, or prostate cancer.
1 - 43 . (canceled)
44 . A method of treating breast cancer in a subject having an estrogen receptor alpha-positive cancer that has a mutant estrogen receptor alpha comprising administering to said subject a therapeutically effective amount of a combination of an m-TOR inhibitor selected from the group consisting of sirolimus, temsirolimus, everolimus, and ridafarolimus, and RAD1901 having the structure:
or a salt or solvate thereof.
45 . The method of claim 44 wherein said breast cancer is a drug resistant breast cancer and is resistant to one or more antiestrogen and/or or aromatase inhibitor therapies.
46 . The method of claim 45 wherein said one or more antiestrogens are selected from the group consisting of tamoxifen, toremifene and fulvestrant and said one or more aromatase inhibitors are selected from the group consisting of aromasin, letrozole and anastrozole.
47 . The method according to claim 44 wherein said subject expresses at least one mutant estrogen receptor alpha selected from the group consisting of D538G, Y537S, Y537N, Y537C, E380Q, S463P, L536R, L536Q, P535H, V392I and V534E.
48 . The method of claim 47 wherein said mutant estrogen receptor alpha is selected from the group consisting of Y537S, Y537N, Y537C, D538G, L536R, S463P and E380Q
49 . The method according to claim 44 wherein said RAD1901 is administered in a total daily dosage of from between 100 mg and 1,000 mg.
50 . The method according to claim 49 wherein said RAD1901 is administered in a total daily dosage of 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg or 1,000 mg.
51 . The method according to claim 49 , wherein said daily dosage is delivered in two separate doses.
52 . The method according to claim 51 wherein said separate doses are equal doses.
53 . The method according to claim 44 wherein said subject is a post-menopausal woman.
54 . The method according to claim 44 wherein said subject is first identified for treatment through measuring for increased expression of one or more genes selected from ABL1, AKT1, AKT2, ALK, APC, AR, ARID1A, ASXL1, ATM, AURKA, BAP, BAP1, BCL2L11, BCR, BRAF, BRCA1, BRCA2, CCND1, CCND2, CCND3, CCNE1, CDH1, CDK4, CDK6, CDK8, CDKN1A, CDKN1B, CDKN2A, CDKN2B, CEBPA, CTNNB1, DDR2, DNMT3A, E2F3, EGFR, EML4, EPHB2, ERBB2, ERBB3, ESR1, EWSR1, FBXW7, FGF4, FGFR1, FGFR2, FGFR3, FLT3, FRS2, HIF1A, HRAS, IDH1, IDH2, IGF1R, JAK2, KDM6A, KDR, KIF5B, KIT, KRAS, LRP1B, MAP2K1, MAP2K4, MCL1, MDM2, MDM4, MET, MGMT, MLL, MPL, MSH6, MTOR, MYC, NF1, NF2, NKX2-1, NOTCH1, NPM, NRAS, PDGFRA, PIK3CA, PIK3R1, PML, PTEN, PTPRD, RARA, RB1, RET, RICTOR, ROS1, RPTOR, RUNX1, SMAD4, SMARCA4, SOX2, STK11, TET2, TP53, TSC1, TSC2, and VHL.
55 . The method according to claim 54 wherein said one or more genes is selected from AKT1, AKT2, BRAF, CDK4, CDK6, PIK3CA, PIK3R1 and MTOR.
56 . The method according to claim 44 wherein said m-TOR inhibitor is dosed at from between 1 mg and 500 mg daily.
57 . The method according to claim 56 wherein said m-TOR inhibitor is dosed at from between 5 mg and 100 mg daily.
58 . The method according to claim 44 , wherein said m-TOR inhibitor is everolimus.
59 . The method according to claim 58 wherein said everolimus is dosed at a daily dose of 10 mg.
60 . The method according to claim 58 wherein said everolimus is dosed at a daily dose from between 2.5 mg and 7.5 mg.
61 . The method according to claim 44 wherein said m-TOR inhibitor is dosed once per day.