TY - JOUR
T1 - Molecular profiling of metastatic bladder cancer early-phase clinical trial participants predicts patient outcomes
AU - Alhalabi, Omar
AU - Hahn, Andrew W.
AU - Msaouel, Pavlos
AU - Andreev-Drakhlin, Alexander Y.
AU - Meric-Bernstam, Funda
AU - Naing, Aung
AU - Piha-Paul, Sarina
AU - Janku, Filip
AU - Pant, Shubham
AU - Yap, Timothy A.
AU - Hong, David S.
AU - Fu, Siqing
AU - Karp, Daniel
AU - Campbell, Erick
AU - Le, Hung
AU - Campbell, Matthew T.
AU - Shah, Amishi Y.
AU - Tannir, Nizar M.
AU - Siefker-Radtke, Arlene O.
AU - Gao, Jianjun
AU - Roszik, Jason
AU - Subbiah, Vivek
N1 - Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2021/3/1
Y1 - 2021/3/1
N2 - Prognosis for patients with metastatic bladder carcinoma (mBC) remains limited and in need of novel therapies. We retrospectively analyzed medical records of 43 patients with platinum-refractory metastatic bladder cancer (mBC) who participated in one or more phase I trials of various investigational therapies. Patients' tumors or circulating tumor DNA were analyzed by next-generation sequencing. The median progression-free survival was 4.2 months, the median overall survival was 9.6 months, and the overall response rate was 17.5%. TP53, ERBB2, PI3KCA, FGFR3, and ARID1A alterations were detected in 66%, 29%, 27%, 24%, and 22% of all patients, respectively. Alterations in FGFR3 were almost mutually exclusive of TP53. More than half (64%) of patients with an FGFR alt received an FGFR inhibitor, 67% of which achieved disease control. Among patients with urothelial carcinoma histology, those harboring a TP53 alteration had a shorter median progression-free survival (PFS) compared with those whose tumors carry wild-type TP53. The reverse relationship was observed in patients harboring an FGFR alteration.
AB - Prognosis for patients with metastatic bladder carcinoma (mBC) remains limited and in need of novel therapies. We retrospectively analyzed medical records of 43 patients with platinum-refractory metastatic bladder cancer (mBC) who participated in one or more phase I trials of various investigational therapies. Patients' tumors or circulating tumor DNA were analyzed by next-generation sequencing. The median progression-free survival was 4.2 months, the median overall survival was 9.6 months, and the overall response rate was 17.5%. TP53, ERBB2, PI3KCA, FGFR3, and ARID1A alterations were detected in 66%, 29%, 27%, 24%, and 22% of all patients, respectively. Alterations in FGFR3 were almost mutually exclusive of TP53. More than half (64%) of patients with an FGFR alt received an FGFR inhibitor, 67% of which achieved disease control. Among patients with urothelial carcinoma histology, those harboring a TP53 alteration had a shorter median progression-free survival (PFS) compared with those whose tumors carry wild-type TP53. The reverse relationship was observed in patients harboring an FGFR alteration.
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U2 - 10.1158/1541-7786.MCR-20-0751
DO - 10.1158/1541-7786.MCR-20-0751
M3 - Article
C2 - 33323389
AN - SCOPUS:85102260132
SN - 1541-7786
VL - 19
SP - 395
EP - 402
JO - Molecular Cancer Research
JF - Molecular Cancer Research
IS - 3
ER -