Efficacy and safety of first- versus second-generation fibroblast growth factor receptor (FGFR) inhibitors in advanced or metastatic urothelial carcinoma with FGFR alterations: a systematic review and meta-analysis.

INTRODUCTION

We reviewed the clinical studies on fibroblast growth factor receptor (FGFR) inhibitors for the treatment of urothelial carcinoma to conduct the meta-analysis of clinical efficacy and safety, aiming to provide more precise treatment options for patients with FGFR alterations.

METHOD: We performed the literature search and screening, then calculated and analyzed using the STATA 14.0 software and Review Manager 5.3 software.

RESULTS

A total of 1528 patients from seventeen studies focusing on seven different FGFR inhibitors were collected. The efficacy analysis indicated the pooled objective response rate (ORR) was 32% (95% CI 26% to 39%) and the pooled disease control rate (DCR) was 64% (95% CI 53% to 75%) for patients with FGFR alterations treated with FGFR inhibitors. The pooled ORR and DCR of second-generation FGFR inhibitors were both significantly higher than those of first-generation FGFR inhibitors (ORR: 0.35, 95% CI 0.29 to 0.41 versus 0.07, 95% CI 0.02 to 0.16, p < 0.001; DCR: 0.68, 95% CI 0.61 to 0.75 versus 0.27, 95% CI 0.16 to 0.40, p < 0.001). The safety analysis indicated any-grade TRAEs were comparable between first- and second-generation FGFR inhibitors, but grade ≥3 TRAEs were significantly less frequent with second-generation FGFR inhibitors versus first-generation FGFR inhibitors (0.49, 95% CI 0.40 to 0.57 versus 0.67, 95% CI 0.57 to 0.76; p = 0.006). The common target toxicities associated with FGFR inhibitors, such as hyperphosphatemia, stomatitis and PPES, were more frequently occurred in second-generation FGFR inhibitors compared to first-generation FGFR inhibitors.

CONCLUSION

The second-generation FGFR inhibitors have advantages in both efficacy and safety, but special adverse reactions still require additional attention.