Correlation between fibroblast growth factor receptor mutation, programmed death ligand-1 expression and survival in urinary bladder cancer based on real-world data.

Background: Programmed cell death (PD)-1/PD-ligand 1 (PD-L1) inhibitors have made a breakthrough in the therapy of advanced urothelial bladder cancer (UBC). The impact of Fibroblast Growth Factor Receptor 3 (FGFR3) mutation on the effectiveness of PD-L1 treatment remains still unclear. Objective: Our study aimed to investigate the frequency of FGFR mutations at different tumor stages, and their relation to PD-L1 status and survival. Methods: 310 patients with urothelial bladder cancer and subsequent radical cystectomy were included in a retrospective study over a 10-year study period at the University of Szeged, Hungary. FGFR3 mutations from the most infiltrative areas of the tumor were analyzed by targeted next-generation sequencing and PD-L1 (28-8 DAKO) tests (tumor positive score -TPS and combined positives score-CPS). In T0 cases FGFR3 mutations were analyzed from the earlier resection samples. Survival and oncological treatment data were collected from the National Health Insurance Fund (NHIF). Neoadjuvant, adjuvant and palliative conventional chemotherapies were allowed; immunotherapies were not. The relationship between the covariates was tested using chi-square tests, and survival analysis was performed using the Kaplan-Meier model and Cox proportional hazards regression. Results: PD-L1 and FGFR could be tested successfully in 215 of the 310 UBC samples [pT0cyst 19 (8.8%); St.0-I 43 (20%); St.II 41 (19%); St.III-IV 112 (52%)]. Significant pairwise dependency was found between tumor stage, FGFR3 mutation status and PD-L1 expression (p < 0.01). Samples with FGFR mutation were more common in less advanced stages and were also less likely to demonstrate PD-L1 expression. The effect of all investigated factors on survival was found to correlate with tumor stage. Conclusion: FGFR alteration frequency varied between the different stages of cancer. Higher positivity rates were observed at early stages, but lower levels of PD-L1 expression were detected in patients with FGFR mutations across at all stages of the disease.

[Multicentric Hungarian results of cabozantinib therapy in patients with metastatic kidney cancer based on real-world data]. / Áttétes vesedaganatos betegek kabozantinibterápiájának multicentrikus magyarországi eredményei.

The aim of our analysis was to evaluate the efficacy of cabozantinib in patients with metastatic renal cell carcinoma. Cabozantinib therapy initiated between 01/01/2019 and 31/12/2022 was evaluated based on a retrospective review of data from 14 renal centers in Hungary. The starting dose was 60 or 40 mg. Physical examinations and laboratory tests were performed every 4 weeks and imaging studies 3-monthly. Tumor response was assessed according to RECIST 1.1, and toxicity according to NCI CTCAE 4.0. A total of 230 patient records were evaluated, 201 (87.4%) of them had clear cell RCC. Cabozantinib was administered as third, second and first-line treatment in 48.7%, 38.3% and <5% of cases, respectively. Dose reductions occurred in 62.6% and treatment interruption in 6.5%. Duration of therapy was 10.03 months, which was independent of dose reduction. Overall tumor response rate was 39.2% and clinical benefit was 82.8%. The duration of first-, second-, third- and fourth-line treatment was 11.47, 8.03, 11.57 and 10.13 months, respectively. Overall survival from the start of therapy was 22.0 months. Cabozantinib therapy in daily practice was more beneficial than according to registry study results. Dose reduction did not affect efficacy.

[Multicentric Hungarian results of cabozantinib therapy in patients with metastatic kidney cancer based on real-world data]. / Áttétes vesedaganatos betegek kabozantinibterápiájának multicentrikus magyarországi eredményei.

The aim of our analysis was to evaluate the efficacy of cabozantinib in patients with metastatic renal cell carcinoma. Cabozantinib therapy initiated between 01/01/2019 and 31/12/2022 was evaluated based on a retrospective review of data from 14 renal centers in Hungary. The starting dose was 60 or 40 mg. Physical examinations and laboratory tests were performed every 4 weeks and imaging studies 3-monthly. Tumor response was assessed according to RECIST 1.1, and toxicity according to NCI CTCAE 4.0. A total of 230 patient records were evaluated, 201 (87.4%) of them had clear cell RCC. Cabozantinib was administered as third, second and first-line treatment in 48.7%, 38.3% and <5% of cases, respectively. Dose reductions occurred in 62.6% and treatment interruption in 6.5%. Duration of therapy was 10.03 months, which was independent of dose reduction. Overall tumor response rate was 39.2% and clinical benefit was 82.8%. The duration of first-, second-, third- and fourth-line treatment was 11.47, 8.03, 11.57 and 10.13 months, respectively. Overall survival from the start of therapy was 22.0 months. Cabozantinib therapy in daily practice was more beneficial than according to registry study results. Dose reduction did not affect efficacy.