Molecular Profiling of Metastatic Bladder Cancer Early-Phase Clinical Trial Participants Predicts Patient Outcomes
| Autor: | Amishi Yogesh Shah, Pavlos Msaouel, Siqing Fu, Hung Le, Timothy A. Yap, Vivek Subbiah, Sarina Anne Piha-Paul, Janku Filip, David S. Hong, Funda Meric-Bernstam, Erick Campbell, Alexander Y. Andreev-Drakhlin, Aung Naing, Matthew T. Campbell, Daniel D. Karp, Shubham Pant, Jianjun Gao, Jason Roszik, Arlene O. Siefker-Radtke, Andrew W. Hahn, Omar Alhalabi, Nizar M. Tannir |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Oncology Cancer Research medicine.medical_specialty ARID1A business.industry Medical record Histology medicine.disease Metastatic bladder cancer Clinical trial 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Text mining 030220 oncology & carcinogenesis Internal medicine medicine Cancer research Carcinoma business Early phase Molecular Biology |
| Zdroj: | Molecular Cancer Research. 19:395-402 |
| ISSN: | 1557-3125 1541-7786 |
| Popis: | 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. Implications: Patients with platinum-refractory mBC derive clinical benefit from participating in early-phase clinical trials and their survival outcomes correlate with the genetic profile of the tumor. Visual Overview: http://mcr.aacrjournals.org/content/molcanres/19/3/395/F1.large.jpg. |
| Databáze: | OpenAIRE |
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