FGFR tyrosine kinase inhibitors for the treatment of urothelial carcinoma
Described here are methods of treating urothelial carcinoma in a patient comprising evaluating a biological sample from the patient for the presence of at least two fibroblast growth factor receptor (FGFR) genetic alterations and treating the patient with an FGFR inhibitor. Also described herein are methods of treating urothelial carcinoma in a patient harboring at least two fibroblast growth factor receptor (FGFR) genetic alterations comprising administering a FGFR inhibitor.
1 . A method of treating urothelial carcinoma harboring at least two FGFR3 mutations comprising FGFR3 G370C and FGFR3 S249C: FGFR3 R248C and FGFR3 Y373C: or FGFR3 S249C and FGFR3 Y373C, in a patient, the method comprising administering a FGFR inhibitor to the patient.
2 . The method of claim 1 further comprising evaluating a biological sample from the patient for the presence of the at least two FGFR3 mutations prior to administering the FGFR inhibitor.
3 . The method of claim 1 , wherein the urothelial carcinoma is locally advanced or metastatic.
4 . The method of claim 2 , wherein the biological sample is blood, lymph fluid, bone marrow, a solid tumor sample, or any combination thereof.
5 . The method of claim 1 , wherein the FGFR inhibitor is erdafitinib.
6 . The method of claim 5 , wherein erdafitinib is administered daily.
7 . The method of claim 5 , wherein erdafitinib is administered orally.
8 . The method of claim 5 , comprising administering erdafitinib orally at a dose of about 8 mg once daily.
9 . The method of claim 8 , wherein the dose of erdafitinib is increased from 8 mg once daily to 9 mg once daily at 14 to 21 days after initiating treatment if:
(a) the patient exhibits a serum phosphate (PO4) level that is less than 5.5 mg/dL at 14-21 days after initiating treatment; and
(b) administration of erdafitinib at 8 mg once daily resulted in no ocular disorder or
administration of erdafitinib at 8 mg once daily resulted in no Grade 2 or greater adverse reaction.
10 . The method of claim 5 , wherein erdafitinib is administered in the form of a tablet.
11 . The method of claim 1 , wherein the FGFR inhibitor is erdafitinib or a pharmaceutically acceptable salt thereof.
12 . The method of claim 1 , wherein the at least two FGFR3 mutations comprise FGFR3 G370C and FGFR3 S249C.
13 . The method of claim 1 , wherein the at least two FGFR3 mutations comprise FGFR3 R248C and FGFR3 Y373C.
14 . The method of claim 1 , wherein the at least two FGFR3 mutations comprise FGFR3 S249C and FGFR3 Y373C.
15 . The method of claim 8 , wherein the at least two FGFR3 mutations comprise FGFR3 G370C and FGFR3 S249C.
16 . The method of claim 8 , wherein the at least two FGFR3 mutations comprise FGFR3 R248C and FGFR3 Y373C.
17 . The method of claim 8 , wherein the at least two FGFR3 mutations comprise FGFR3 S249C and FGFR3 Y373C.
18 . The method of claim 9 , wherein the at least two FGFR3 mutations comprise FGFR3 G370C and FGFR3 S249C.
19 . The method of claim 9 , wherein the at least two FGFR3 mutations comprise FGFR3 R248C and FGFR3 Y373C.
20 . The method of claim 9 , wherein the at least two FGFR3 mutations comprise FGFR3 S249C and FGFR3 Y373C.
21 . The method of claim 3 , wherein the FGFR inhibitor is erdafitinib and the method comprises administering erdafitinib orally at a dose of about 8 mg once daily.
22 . The method of claim 21 , wherein the dose of erdafitinib is increased from 8 mg once daily to 9 mg once daily at 14 to 21 days after initiating treatment if:
(a) the patient exhibits a serum phosphate (PO4) level that is less than 5.5 mg/dL at 14-21 days after initiating treatment; and
(b) administration of erdafitinib at 8 mg once daily resulted in no ocular disorder or administration of erdafitinib at 8 mg once daily resulted in no Grade 2 or greater adverse reaction.
23 . The method of claim 21 , wherein the at least two FGFR3 mutations comprise FGFR3 G370C and FGFR3 S249C.
24 . The method of claim 21 , wherein the at least two FGFR3 mutations comprise FGFR3 R248C and FGFR3 Y373C.
25 . The method of claim 21 , wherein the at least two FGFR3 mutations comprise FGFR3 S249C and FGFR3 Y373C.
26 . The method of claim 22 , wherein the at least two FGFR3 mutations comprise FGFR3 G370C and FGFR3 S249C.
27 . The method of claim 22 , wherein the at least two FGFR3 mutations comprise FGFR3 R248C and FGFR3 Y373C.
28 . The method of claim 22 , wherein the at least two FGFR3 mutations comprise FGFR3 S249C and FGFR3 Y373C.