Abstract 768P
Background
Only some urinary tract carcinoma patients benefit from second- and later line of immunotherapy. No prognostic scores are well-established to predict which patients most likely benefit from immunotherapy.
Methods
In the Italian cohort of the SAUL trial a combination of baseline SII (Neutrophil-to-lymphocyte x Platelets), PD-L1 expression on tumour-infiltrating immune cells (IC) +/- LDH was post hoc assessed according to progression-free survival (PFS), overall survival (OS) and disease control rate (DCR). The SII cut-off was identified by the ROC curve.
Results
267 patients were treated with atezolizumab as 2nd (83%) and >3rd line therapy (17%). The median age was 69 years, 54% had ECOG performance status (PS) 0 and 83% were male; 96% had urothelial histology and 76% had bladder cancer. The combination of SII and PD-L1 +/- LDH identified three prognostic groups as low (PD-L1 IC 2-3, SII<884 +/- LDH ≤ upper limit of normal - ULN), high (PD-L1 IC 0-1, SII≥884 +/- LDH>ULN) and intermediate (other combinations) which correlated with PFS, OS and DCR. Multivariate analyses adjusted for sex, age, PS, creatinine clearance, liver and lymph-nodes metastases, confirmed all the statistically significant correlations (see Table). Table: 768P
| Biomarkers | Prognostic group | Patients | mPFS (months) | Adjusted Hazard Ratio (95% CI) | p value | mOS (months) | Adjusted Hazard Ratio (95% CI) | p value | DCR | Odds Ratio (95% CI)) | p value |
| PD-L1 + SII | Low | 15% | 8.2 | 1 (Ref) | NR | 1 (Ref) | 73.5% | 1 (Ref) | |||
| Intermediate | 48% | 2.4 | 1.70 (1.03-2.79) | 11.9 | 1.62 (0.80-3.24) | 44.6% | 0.33 (0.13-0.83) | ||||
| High | 37% | 2 | 2.62 (1.55-4.44) | <0.0001 | 4.6 | 3.04 (1.50-6.19) | <0.0001 | 23% | 0.12 (0.04-0.33) | <0.001 | |
| PD-L1 + SII + LDH | Low | 12% | 10.8 | 1 (Ref) | NR | 1 (Ref) | 75% | 1 (Ref) | |||
| Intermediate | 77% | 2.2 | 2.18 (1.25-3.79) | 9.5 | 2.90 (1.25-6.77) | 38% | 0.22 (0.08-0.60) | ||||
| High | 11% | 2.1 | 3.66 (1.85-7.23) | <0.0001 | 3.1 | 7.39 (2.83-19.31) | <0.0001 | 16% | 0.07 (0.02-0.31) | <0.001 |
Conclusions
This analysis of the SAUL trial showed that the combination of SII, PD-L1 and LDH – better than SII and PDL-1 - might stratify patients with advanced urinary tract carcinoma according to their outcome following atezolizumab immunotherapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Roche Spa.
Funding
Roche Spa.
Disclosure
S.E. Rebuzzi: Research grant/Funding (institution): Roche. C.N. Sternberg: Advisory/Consultancy: Pfizer; Advisory/Consultancy: MSD; Advisory/Consultancy: Merck; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Astellas; Advisory/Consultancy: Sanofi-Genzyme; Advisory/Consultancy: Roche _ Genentech; Advisory/Consultancy: Incyte; Advisory/Consultancy: Mescape; Advisory/Consultancy: Urotoday. G. Fornarini: Advisory/Consultancy: MSD; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Merck; Advisory/Consultancy: Astellas; Advisory/Consultancy: Sanofy Genzime; Advisory/Consultancy: Janssen; Advisory/Consultancy: Roche Genentech. F. Calabro': Research grant/Funding (institution): Roche. C. Baldessari: Travel/Accommodation/Expenses: Astellas; Travel/Accommodation/Expenses: Pierre Fabre; Research grant/Funding (institution): Roche . G. Scandurra: Research grant/Funding (institution): Roche. U. De giorgi: Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (institution): Sanofi ; Advisory/Consultancy: Astellas; Advisory/Consultancy: Bayer; Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen; Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Advisory/Consultancy: Merck; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer. C. Masini: Speaker Bureau/Expert testimony: BMS; Speaker Bureau/Expert testimony: Janssen; Speaker Bureau/Expert testimony: Ipsen; Speaker Bureau/Expert testimony: Pfizer; Speaker Bureau/Expert testimony: MSD; Speaker Bureau/Expert testimony: Astellas; Speaker Bureau/Expert testimony: Novartis. C. Caserta: Honoraria (self): MSD; Honoraria (self): Janssen; Honoraria (self): BMS; Honoraria (self): Pfizer. L. Galli: Research grant/Funding (institution): Roche. M. Maruzzo: Research grant/Funding (institution): Roche. I. Zampiva: Research grant/Funding (institution): Roche. C. Buttigliero: Research grant/Funding (institution): Roche. C. Astolfi: Full/Part-time employment: Roche. G.L. Banna: Honoraria (self): Janssen Cilag; Honoraria (self): Boeringher Ingelheim; Honoraria (self): Roche; Non-remunerated activity/ies: BMS; Non-remunerated activity/ies: AstraZeneca Medimmune; Non-remunerated activity/ies: Pierre Fabre; Non-remunerated activity/ies: Ipsen. All other authors have declared no conflicts of interest.