METHODS FOR TREATMENT OF BREAST CANCER NONRESPONSIVE TO TRASTUZUMAB
The present invention provides a method of treating breast cancer that is nonresponsive to treatment with trastuzumab, comprising administering to a subject in need of such treatment a therapeutically effective amount of compound N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, or a pharmaceutically acceptable salt thereof.
1 . A method of treating breast cancer that is nonresponsive to treatment with trastuzumab, comprising administering to a subject in need of such treatment a therapeutically effective amount of a compound of Formula 1
or a pharmaceutically acceptable salt thereof.
2 . A compound of Formula 1
or a pharmaceutically acceptable salt thereof, for use in treating breast cancer that is nonresponsive to treatment with trastuzumab.
3 . Use of a compound of Formula 1
or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for treating breast cancer that is nonresponsive to treatment with trastuzumab.
4 . The method of claim 1 , wherein the compound, or a pharmaceutically acceptable salt thereof, is a stereoisomer selected from the group consisting of N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine and N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, or a pharmaceutically acceptable salt of the stereoisomer.
5 . The method as in claim 1 or 4 , wherein the pharmaceutically acceptable salt is the salt of p-toluenesulfonic acid.
6 . The method as in claim 1 , 4 or 5 , wherein the subject is human and the breast cancer has not been treated with trastuzumab.
7 . The method as in claim 1 , 4 or 5 , wherein the subject is human and the breast cancer has been treated with trastuzumab.
8 . The method as in claim 1 , 4 or 5 , comprising co-administering the compound of Formula 1 and trastuzumab.
9 . The method as in claim 1 , 4 or 5 , wherein the subject is human and the breast cancer is PTEN-negative.
10 . The method as in claim 1 , 4 or 5 , wherein the subject is human and the breast cancer is positive for mutations in the PIK3CA gene.
11 . The method as in claim 1 , 4 or 5 , wherein the subject is human and the breast cancer expresses a truncated ErbB2 receptor that lacks the extracellular domain to which trastuzumab binds.
12 . The method as in claim 1 , 4 or 5 , wherein the subject is human and the breast cancer overexpresses one or more RTKs selected from the group consisting of EGFR family members, IGF-1R and HGFR.