Prognostic Role of FGFR Alterations and FGFR mRNA Expression in Metastatic Urothelial Cancer Undergoing Checkpoint Inhibitor Therapy - 09/12/21
, Hendrik Jütte 2, †, Ralph M. Wirtz 3, ⁎, Jonas Jarczyk 4, ⁎, Ademi Santiago-Walker 5, Friedemann Zengerling 6, ⁎, Johannes Breyer 7, ⁎, Danijel Sikic 8, ⁎, Maximilian C. Kriegmair 4, ⁎, Jost von Hardenberg 4, Bernd Wullich 8, ⁎, Helge Taubert 8, ⁎, Veronika Weyerer 9, ⁎, Robert Stoehr 9, ⁎, Christian Bolenz 6, ⁎, Maximilian Burger 7, ⁎, Stefan Porubsky 10, ⁎, Arndt Hartmann 9, ⁎, Florian Roghmann 1, ⁎, Philipp Erben 4, †, ⁎, Markus Eckstein 9, †, ⁎Abstract |
Objective |
To examine the disease-specific survival(DSS) after checkpoint inhibitor(CPI) therapy based on FGFR alterations and FGFR mRNA expression levels in patients with metastatic urothelial cancer(mUCa) within a multi-center cohort.
Methods |
Within a cohort of 72 patients with mUCa from five academic centers in Germany FGFR alterations, as well as FGFR1-4 mRNA expression levels in tumor samples from the primary tumor or metastatic sites. Spearman rank correlations, logistic regression, as well as Kaplan-Meier survival analyses and univariate Cox proportional hazards regression models were employed to examine the impact of different FGFR patterns on the DSS after CPI treatment.
Results |
FGFR3 mutations or gene fusions (gene alterations) were detected in 16.9% of all samples. Patients with or without FGFR3 gene alterations did not show different oncological outcomes undergoing CPI treatment.
Low expression of FGFR2 mRNA alone, as well as the combination of either low FGFR2mRNA expression and FGFR3 gene alteration or high FGFR3mRNA expression (P = 0.027), identified a subgroup of patients with unfavorable outcomes, comprising 40% of the total cohort. This trend was also observed in univariate Cox proportional hazards regression analysis(FGFR3 gene alteration: Hazard ratio(HR) 5.33, 95%Confidence interval(CI)1.76-15.0, P = 0.004; FGFR3mRNA expression:HR 3.04, 95%CI 1.40-7.13, P = 0.005).
Conclusion |
Assessment of FGFR mRNA expression identified a high-risk subgroup of patients with mUCa. These patients showing overexpression of FGFR3 mRNA were found to have unfavorable DSS after CPI treatment. Using this approach may be suitable for identifying a patient population with poor response to CPI treatment, which may benefit from early FGFR inhibition.
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| Funding: STRATIFYER carried out gene expression analyses. Janssen Research & Development gave research support for this work. |
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| Disclosures: HJ receives speaker's honoraria Roche, AstraZeneca, BMS, |
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| MSD, and Ipsen. RMW Leadership role: CEO & CSO, STRATIFYER Molecular Pathology GmbH. FZ receives speaker's honoraria from Bayer Health, BMS, IPSEN, Novartis, Roche Sanofi/Aventis, and Pfizer. Advisory role: BMS, Novartis, Roche, Sanofi/Aventis, Merck Serono GmbH, IPSEN, and Merck Sharp & Dohme. Travel costs: Bayer Health, Ipsen, Janssen-Cilag, Novartis, and Pfizer. JB receives research funding from Janssen, and Cepheid. Speaker's honoraria: Ipsen, Pfizer, BMS, AstraZeneca, and Merck. CB receives speaker honoraria from Janssen-Cilag, Astra Zeneca, medac, Takeda, Roche, and ERBE research funds. AH receives research funding from Janssen, AstraZeneca, Cepheid, Roche, Nanostring, Biontech, and Illumina. Advisory Role: BMS, MSD, Cepheid, Qiagen, Roche, Janssen, AstraZeneca, Ipsen, Abbive, Nanostring, and Diateutics. Speaker's honoraria: BMS, MSD, Cepheid, Qiagen, Roche, Boehringer Ingelheim, Janssen, AstraZeneca, Nanostring, and 3D Histotech. FR receives research funding from Janssen. Advisory board for Janssen and Roche. Speaker's honoraria: Ipsen, Roche, Janssen, and Merck. PE receives research funding from Janssen Research & Development. ME receives research funding from Janssen, STRATIFYER, AstraZeneca. Advisory role for AstraZeneca, Janssen, and Diaceutics, GenomicHealth. Speaker's honoraria & travel costs: AstraZeneca, Janssen, Diaceutics, Roche, Astellas, MSD. |
Vol 157
P. 93-101 - novembre 2021 Retour au numéro
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