Sequencing chemotherapy and immune checkpoint inhibitors (ICI) in metastatic urothelial carcinoma (UC): Meet-Uro1 study.

person Marco Bandini Vita-Salute San Raffaele University, Milan, Italy info_outline Marco Bandini, Elena Farè, Daniele Raggi, Ugo De Giorgi, Giuseppe Luigi Banna, Umberto Basso, Tania Losanno, Melissa Bersanelli, Sebastiano Buti, Daniele Santini, Claudia Mucciarini, Marcello Tucci, Rosa Tambaro, Azzurra Farnesi, Corrado Ficorella, Orazio Caffo, Emanuele Naglieri, Filippo Pederzoli, Sandro Pignata, Andrea Necchi

Authors person Marco Bandini Vita-Salute San Raffaele University, Milan, Italy info_outline Marco Bandini, Elena Farè, Daniele Raggi, Ugo De Giorgi, Giuseppe Luigi Banna, Umberto Basso, Tania Losanno, Melissa Bersanelli, Sebastiano Buti, Daniele Santini, Claudia Mucciarini, Marcello Tucci, Rosa Tambaro, Azzurra Farnesi, Corrado Ficorella, Orazio Caffo, Emanuele Naglieri, Filippo Pederzoli, Sandro Pignata, Andrea Necchi Organizations Vita-Salute San Raffaele University, Milan, Italy, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy, Cannizzaro Hospital, Catania, Italy, Oncologia 1 - Istituto Oncologico Veneto IOV - IRCCS, Padova, Italy, San Camillo Forlanini Hospital, Rome, Italy, Medical Oncology Unit, University Hospital of Parma, Parma, Italy, Department of Medical Oncology, Campus Bio-Medico - University of Rome, Rome, Italy, Department of Oncology and Haematology, Ramazzini Hospital, Carpi, Italy, Department of Oncology, University of Turin; San Luigi Gonzaga Hospital, Orbassano (TO), Italy, Istituto Nazionale Tumori IRCCS, Fondazione Pascale, Napoli, Italy, Oncologia Medica, Livorno, Italy, San Salvatore Hospital, University of L'Aquila, L'aquila, Italy, Santa Chiara Hospital, Trento, Italy, National Cancer Centre, Istituto Tumori Giovanni Paolo II, Bari, Italy, Università Vita-Salute San Raffaele, Milan, Italy, National Cancer Institute of Naples, Naples, Italy Abstract Disclosures Research Funding Other Background: Several ICI are now approved in different therapeutic settings of metastatic UC. The identification of the optimal therapeutic sequence that includes standard chemotherapy (CT) use is a key objective of further research, mainly in the first-line (1L) setting. In this study, we analyzed the pathways of treatment post-ICI and focused on the effects of CT post-ICI in both 1L and salvage-line (≥2L) therapy of metastatic UC. Methods: Data from 15 Italian centers were collected. Patients (pts) should have received ICI in any line of treatment for metastatic UC and have experienced a disease progression (PD) according to RECIST 1.1. Cox regression analyses were performed within the subgroups, and adjusted Kaplan-Meier curves analyzed the progression-free survival (PFS) and overall survival (OS) post-ICI PD, according to the treatment line. Results: 278 pts (79 in 1L; 199 ≥2L) were analyzed. In total, after ICI, pts were treated with CT (N = 69), ICI beyond PD (N = 20) or no treatment (N = 189). Features associated with no therapy post-ICI were rapid PD on ICI (p < 0.001) and number of metastatic sites (p = 0.002). The objective response (OR) to CT post-ICI was 23.1% in 1L, and 18.5% in ≥2L. Median PFS was 5 months (m) in 1L and 3m ≥2L, median OS on CT was 13m in 1L and 9m ≥2L. Post-ICI CT was not significantly associated with improved OS in 1L on multivariable analyses (MVA): HR: 0.43 (95%CI: 0.15-1.23), but it was significant in MVA in ≥2L pts (HR: 0.22, 95%CI: 0.10-0.48). The type of previous ICI (combination-ICI vs single-agent ICI, p = 0.789), as well as the OR to previous ICI (p = 0.871) had no effect on OS with sequential CT on MVA. In the total population adjusted by line, median OS post-CT was 17m (range 15-NA), and with ICI beyond PD was 8m (6-NA) (p < 0.001). Conclusions: This large multicentric appraisal indicated that CT post-salvage ICI is endowed with similar activity and efficacy compared to ICI-naïve pts. Conversely, CT administered post-ICI in 1L determined less responses and was not significant on MVA. These effects are likely determined by the inability to rescue pts with rapidly aggressive disease. Shifting to salvage CT at the time of PD on ICI remains the preferable option in all suitable pts.