G Fornarini1, S E Rebuzzi2, G L Banna3, F Calabrò4, G Scandurra5, U De Giorgi6, C Masini7, C Baldessari8, E Naglieri9, C Caserta10, S Manacorda11, M Maruzzo12, M Milella13, C Buttigliero14, R Tambaro15, P Ermacora16, F Morelli17, F Nolè18, C Astolfi19, C N Sternberg20. 1. Medical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, Genova, Italy. 2. Medical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, Genova, Italy; Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy. 3. Department of Oncology, Portsmouth Hospitals University NHS Trust, Portsmouth, UK. 4. Medical Oncology, Azienda Ospedaliera S. Camillo-Forlanini, Rome, Italy. 5. Medical Oncology, Azienda Ospedaliera Cannizzaro di Catania, Catania, Italy. 6. Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) - IRCCS, Meldola, Italy. 7. Medical Oncology, AUSL-IRCCS di Reggio Emilia, Reggio Emilia, Italy. 8. Oncology, Azienda Ospedaliero - Universitaria di Modena, Modena, Italy. 9. Division of Medical Oncology, IRCCS Istituto Tumori Bari Giovanni Paolo II - IRCCS, Bari, Italy. 10. Medical Oncology Unit, Azienda Ospedaliera S. Maria, Terni, Italy. 11. Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. 12. Medical Oncology Unit 1, Department of Oncology, Istituto Oncologico Veneto, IOV-IRCCS, Padua, Italy. 13. Dipartimento di Oncologia, Policlinico Universitario G.B. Rossi Borgo Roma, Verona, Italy. 14. Medical Oncology, Università degli Studi di Torino, Turin, Italy. 15. U.O.C di Oncologia Sperimentale Uroginecologica, I.N.T. IRCCS Fondazione G. Pascale, Naples, Italy. 16. Dipartimento di Oncologia, Azienda Ospedaliero Universitaria di Udine, Udine, Italy. 17. Casa Sollievo della Sofferenza, S. Giovanni Rotondo, Foggia, Italy. 18. IEO, Istituto Europeo di Oncologia IRCCS, Milan, Italy. 19. Medical Affairs & Clinical Operation, Roche S.p.A., Monza, Italy. 20. Hematology and Oncology, Englander Institute for Precision Medicine Weill Cornell Medicine, New York-Presbyterian, New York, USA. Electronic address: cns9006@med.cornell.edu.
Abstract
BACKGROUND: Reliable and affordable prognostic and predictive biomarkers for urothelial carcinoma treated with immunotherapy may allow patients' outcome stratification and drive therapeutic options. The SAUL trial investigated the safety and efficacy of atezolizumab in a real-world setting on 1004 patients with locally advanced or metastatic urothelial carcinoma who progressed to one to three prior systemic therapies. PATIENTS AND METHODS: Using the SAUL Italian cohort of 267 patients, we investigated the prognostic role of neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) and the best performing one of these in combination with programmed death-ligand 1 (PD-L1) with or without lactate dehydrogenase (LDH). Previously reported cut-offs (NLR >3 and NLR >5; SII >1375) in addition to study-defined ones derived from receiver operating characteristic (ROC) analysis were used. RESULTS: The cut-off values for NLR and SII by the ROC analysis were 3.65 (sensitivity 60.4; specificity 63.0) and 884 (sensitivity 64.4; specificity 67.5), respectively. The median overall survival (OS) was 14.7 months for NLR <3.65 [95% confidence interval (CI) 9.9-not reached (NR)] versus 6.0 months for NLR ≥3.65 (95% CI 3.9-9.4); 14.7 months for SII <884 (95% CI 10.6-NR) versus 6.0 months for SII ≥884 (95% CI 3.7-8.6). The combination of SII, PD-L1, and LDH stratified OS better than SII plus PD-L1 through better identification of patients with intermediate prognosis (77% versus 48%, respectively). Multivariate analyses confirmed significant correlations with OS and progression-free survival for both the SII + PD-L1 + LDH and SII + PD-L1 combinations. CONCLUSION: The combination of immune-inflammatory biomarkers based on SII, PD-L1, with or without LDH is a potentially useful and easy-to-assess prognostic tool deserving validation to identify patients who may benefit from immunotherapy alone or alternative therapies.
BACKGROUND: Reliable and affordable prognostic and predictive biomarkers for urothelial carcinoma treated with immunotherapy may allow patients' outcome stratification and drive therapeutic options. The SAUL trial investigated the safety and efficacy of atezolizumab in a real-world setting on 1004 patients with locally advanced or metastatic urothelial carcinoma who progressed to one to three prior systemic therapies. PATIENTS AND METHODS: Using the SAUL Italian cohort of 267 patients, we investigated the prognostic role of neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) and the best performing one of these in combination with programmed death-ligand 1 (PD-L1) with or without lactate dehydrogenase (LDH). Previously reported cut-offs (NLR >3 and NLR >5; SII >1375) in addition to study-defined ones derived from receiver operating characteristic (ROC) analysis were used. RESULTS: The cut-off values for NLR and SII by the ROC analysis were 3.65 (sensitivity 60.4; specificity 63.0) and 884 (sensitivity 64.4; specificity 67.5), respectively. The median overall survival (OS) was 14.7 months for NLR <3.65 [95% confidence interval (CI) 9.9-not reached (NR)] versus 6.0 months for NLR ≥3.65 (95% CI 3.9-9.4); 14.7 months for SII <884 (95% CI 10.6-NR) versus 6.0 months for SII ≥884 (95% CI 3.7-8.6). The combination of SII, PD-L1, and LDH stratified OS better than SII plus PD-L1 through better identification of patients with intermediate prognosis (77% versus 48%, respectively). Multivariate analyses confirmed significant correlations with OS and progression-free survival for both the SII + PD-L1 + LDH and SII + PD-L1 combinations. CONCLUSION: The combination of immune-inflammatory biomarkers based on SII, PD-L1, with or without LDH is a potentially useful and easy-to-assess prognostic tool deserving validation to identify patients who may benefit from immunotherapy alone or alternative therapies.
Authors: Sara Elena Rebuzzi; Alessio Signori; Marco Stellato; Daniele Santini; Marco Maruzzo; Ugo De Giorgi; Paolo Pedrazzoli; Luca Galli; Paolo Andrea Zucali; Emanuela Fantinel; Claudia Carella; Giuseppe Procopio; Michele Milella; Francesco Boccardo; Lucia Fratino; Roberto Sabbatini; Riccardo Ricotta; Stefano Panni; Francesco Massari; Mariella Sorarù; Matteo Santoni; Alessio Cortellini; Veronica Prati; Hector Josè Soto Parra; Francesco Atzori; Marilena Di Napoli; Orazio Caffo; Marco Messina; Franco Morelli; Giuseppe Prati; Franco Nolè; Francesca Vignani; Alessia Cavo; Giandomenico Roviello; Miguel Angel Llaja Obispo; Camillo Porta; Sebastiano Buti; Giuseppe Fornarini; Giuseppe Luigi Banna Journal: Front Oncol Date: 2022-09-23 Impact factor: 5.738