Journal article
Rogaratinib treatment of patients with advanced urothelial carcinomas prescreened for tumor FGFR mRNA expression.
- Joerger, Markus Kantonsspital, St Gallen, Switzerland;
- Cassier, Philippe Centre Léon Bérard, Lyon, France;
- Penel, Nicolas Centre Oscar Lambret, Lille, France;
- Cathomas, Richard Kantonsspital Graubuenden, Chur, Switzerland;
- Richly, Heike West German Cancer Center, University Hospital Essen, Essen, Germany;
- Schostak, Martin Otto-von-Guericke-Universität Magdeburg, Magdeburg, Germany;
- Janitzky, Andreas Otto-von-Guericke-Universität Magdeburg, Magdeburg, Germany;
- Wermke, Martin Carl Gustav Carus Dresden an der Technischen Universität Dresden, Dresden, Germany;
- Nogova, Lucia University Hospital Cologne, Cologne, Germany;
- Tai, David Wai-Meng National Cancer Center Singapore, Singapore, Singapore;
- Sayehli, Cyrus Universitätsklinikum Würzburg, Wuerzburg, Germany;
- Grüllich, Carsten University of Heidelberg, Heidelberg, Germany;
- Grande, Enrique Ramón y Cajal University Hospital, Madrid, Spain;
- Navarro, Alejandra Vall d'Hebron University Hospital, Barcelona, Spain;
- Park, Se Hoon Sungkyunkwan University, Samsung Medical Center, Seoul, Korea, Republic of (South);
- Gillessen, Silke Kantonsspital St. Gallen, St. Gallen, Switzerland;
- Nogai, Hendrik Bayer AG, Berlin, Germany;
- Bender, Sebastian Bayer AG, Wuppertal, Germany;
- Ellinghaus, Peter Bayer AG, Wuppertal, Germany;
- Schuler, Martin H. West German Cancer Center, University Hospital Essen, Essen, Germany;
Published in:
- Journal of Clinical Oncology. - American Society of Clinical Oncology (ASCO). - 2018, vol. 36, no. 6_suppl, p. 494-494
English
494 Background: Activation of FGFR signaling is involved in a variety of malignancies including advanced urothelial cancer (UC). Rogaratinib is an oral pan-FGFR kinase inhibitor. We report here the results from a phase I expansion cohort in UC patients prescreened for FGFR1-3 mRNA expression levels and activating mutations. (NCT01976741) Methods: Patients with advanced urothelial carcinomas were selected based on high FGFR1-3 mRNA expression in biopsy specimens. Selected patients were treated with rogaratinib 800mg twice daily until tumour progression, untolerable toxicity, or withdrawal. Tumor response was assessed by RECIST, v1.1. Adverse events were reported using CTCAE v4.03 criteria. Results: A total of 219 UC patients were prescreened for FGFR1-3 mRNA expression levels and FGFR3 activating mutations, with 99 samples (45%) found to be FGFR-positive. Of those, 87% of samples were positive for FGFR3 mRNA, 5% for FGFR1 mRNA and 8% were double FGFR mRNA-positive (FGFR1/2, 1/3 or 2/3). Frequency of FGFR3 activating mutations in UC samples was 7%, all of which also had high FGFR3 mRNA. Fifty two patients (median prior line of treatment 2) started treatment and 51 were evaluable for response. Rogaratinib was generally well tolerated and AEs manageable with dose modification. The most common AEs were diarrhea (49%) and hyperphosphatemia (49%). Objective response rate (ORR) was 24% (12/51; all PRs) and disease control rate (DCR) was 73% (37/51). Eleven of 12 pts with a PR were positive for FGFR3 mRNA, 5 of whom also had FGFR3 mutations, and one patient was positive for FGFR1 mRNA. Ten FGFR-positive UC patients had prior immuno-oncology (I/O) treatment, 9 of whom had progressive disease as best response. For these 10 patients the ORR was 30% and the DCR 80%. Conclusions: Selection of pts for treatment with rogaratinib based on FGFR mRNA expression levels was feasible and identified drug-sensitive patients with and without underlying DNA alterations. Rogaratinib had a favorable safety profile and showed promising anti-tumor activity in UC patients. Responses and disease stabilization were observed with rogoratinib in UC pts refractory to prior I/O treatment. Clinical trial information: NCT01976741.
- Language
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- English
- Open access status
- closed
- Identifiers
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- DOI 10.1200/jco.2018.36.6_suppl.494
- ISSN 0732-183X
- Persistent URL
- https://sonar.rero.ch/global/documents/51786
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