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 1 trials of various investigational therapies.
Patients' tumors or circulating tumor DNA were analyzed by next generation sequencing. Median progression-free survival was 4.2 months, 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 PFS compared to 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.
Molecular cancer research : MCR. 2020 Dec 15 [Epub ahead of print]
Omar Alhalabi, Andrew W Hahn, Pavlos Msaouel, Alexander Y Andreev-Drakhlin, Funda Meric-Bernstam, Aung Naing, Sarina Piha-Paul, Janku Filip, Shubham Pant, Timothy A Yap, David S Hong, Siqing Fu, Daniel Karp, Erick Campbell, Hung Le, Matthew T Campbell, Amishi Y Shah, Nizar M Tannir, Arlene O Siefker-Radtke, Jianjun Gao, Jason Roszik, Vivek Subbiah
Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center., Cancer Medicine, The University of Texas MD Anderson Cancer Center., Medical Oncology, University of Texas MD Anderson Cancer Center., Department of Hematology and Oncology, The University of Texas MD Anderson Cancer Center., Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center., Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center., Investigatonal Cancer Therapeutics, University of Texas MD Anderson Cancer Center., Department of Investigational Cancer Therapeutics (Phase I Program), The University of Texas MD Anderson Cancer Center., Center for Cancer Research, University of Texas MD Anderson Cancer Center., The University of Texas MD Anderson Cancer Center., University of Texas MD Anderson Cancer Center., Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center., Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center., Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center., Departments of Melanoma Medical Oncology and Genomic Medicine, The University of Texas MD Anderson Cancer Center., Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center .
PubMed http://www.ncbi.nlm.nih.gov/pubmed/33323389