Chemotherapy following immune checkpoint inhibitors in patients with locally advanced or metastatic urothelial carcinoma

Background: Recent studies suggest improvements in response to salvage chemo-therapy (CT) after immune checkpoint inhibitors (ICIs) in several types of cancer. Our objec-tive was to assess the efficacy of chemotherapy re-challenge after ICI, compared with second -line chemotherapy without previous ICI in patients with locally advanced or metastatic ur-othelial carcinoma (la/mUC). Methods: In this multicentre retrospective study, we included all patients with la/mUC initi-ating second or third-line chemotherapy from January 2015 to June 2020. We compared pa-tients treated with second-line chemotherapy without previous ICI (CT2) and patients treated with third-line chemotherapy after ICI (CT3). The primary end-point was objective response rate (ORR) in CT3 compared with CT2. Secondary end-points included progression-free sur-vival (PFS) and toxicities. Results: Overall, 553 patients were included. ORRs were 31.0% (95% CI, 26.5 to 35.5) and 29.2% (95% CI, 21.9 to 36.6), respectively, in CT2 and CT3, with no statistically significant differences (P = 0.62). In subgroup analyses, no differences in ORR were observed by Bell-munt risk group, type of chemotherapy (platinum or taxanes), duration of response to first -platinum-based chemotherapy (< or >= 12 months) or FGFR-status. Median PFS was 4.6 months (95% CI, 3.9 to 5.1) and 4.9 months (95% CI, 4.1 to 5.5) in CT2 and CT3, respectively, and grade 3-4 hematologic toxicity occurred in 35.0% and 22.4% of patients. Conclusion: This large multicentre retrospective study provides clinically relevant real-world data. Chemotherapy re-challenge after ICI in la/mUC achieves ORR and PFS comparable with those obtained in CT2 with an acceptable safety profile. These updated results offer more promising outcomes than historically reported with second-line chemotherapy data. (C) 2022 Elsevier Ltd. All rights reserved.

Automated summary

This study assessed the efficacy of chemotherapy re-challenge after immune checkpoint inhibitors (ICIs) in patients with locally advanced or metastatic urothelial carcinoma and compared it with second-line chemotherapy without previous ICIs. The results showed that chemotherapy re-challenge after ICIs achieved similar objective response rates and progression-free survival as second-line chemotherapy without previous ICIs, with an acceptable safety profile.