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

• Published in: European journal of cancer (1990) Vol. 175; pp. 43 - 53
• Main Authors: Meynard, Lucie, Dinart, Derek, Delaunay, Blandine, Fléchon, Aude, Saldana, Carolina, Lefort, Félix, Gravis, Gwenaëlle, Thiery-Vuillemin, Antoine, Cancel, Mathilde, Coquan, Elodie, Ladoire, Sylvain, Maillet, Denis, Rolland, Frédéric, Boughalem, Elouen, Martin, Sophie, Laramas, Mathieu, Crouzet, Laurence, Abbar, Baptiste, Falkowski, Sabrina, Pouessel, Damien, Roubaud, Guilhem
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-11-2022; Elsevier Science Ltd; Elsevier
• Subjects: Bladder cancer; Cancer; Chemotherapy; Fibroblast growth factor receptors; Immune checkpoint inhibitor; Immune checkpoint inhibitors; Inhibitors; Life Sciences; Metastases; Metastasis; Platinum; Santé publique et épidémiologie; Statistical analysis; Subgroups; Toxicity; Urothelial carcinoma; Immune checkpoint inhibitor; Urothelial carcinoma; Chemotherapy
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2022.08.014

Recent studies suggest improvements in response to salvage chemotherapy (CT) after immune checkpoint inhibitors (ICIs) in several types of cancer. Our objective 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 urothelial carcinoma (la/mUC).
In this multicentre retrospective study, we included all patients with la/mUC initiating second or third-line chemotherapy from January 2015 to June 2020. We compared patients 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 survival (PFS) and toxicities.
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 Bellmunt 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.
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.
•Largest retrospective study on the efficacy of CT re-challenge after ICIs in la/mUC.•Third-line CT after ICIs was not associated with higher ORR compared with second-line CT.•Patients derived comparable benefit of CT in both groups in terms of ORR and PFS.•Chemotherapy remains a good choice as third-line therapy after ICI in la/mUC.