Abstract 777P
Background
ICI have demonstrated clinical benefit and improved survival in mUC. However, outcomes remain poor and predictive markers are not available. Derived neutrophil-to-lymphocyte ratio (dNLR) and immune-related adverse events (irAEs) have been associated with response to ICI in other tumor types. Our aim was to assess the role of these factors in mUC patients treated with ICI.
Methods
Retrospective analysis of a cohort of patients (p) with mUC treated with ICI in our institution between 2016 and 2019. Clinical characteristics were collected. dNLR, defined as neutrophils/(leukocytes-neutrophils), at baseline and at week 3 from first dose was calculated. IrAEs were assessed with CTCAE v.4.0. Survival analysis was made using Kaplan-Meier method. Correlation of clinical factors and outcomes was studied using Chi-squared test and Cox regression.
Results
71 p were included. Median age was 68 years, 54 p (76%) were male, 59 p (83%) had PS-ECOG 0-1, 15 p (21%) were treatment-naïve, 15 p (24%) had elevated LDH 11 p (15.5%) had liver metastases (LM). Patients were treated with pembrolizumab (27 p, 38%), atezolizumab (37p, 52%), nivolumab (5p, 7%), Durvalumab – Tremelimumab (2 p, 3%). Median nº cycles were 4 (1 - 50). Response rate was 31% (95% CI, 21-43). Median overall survival (OS) was 9 months (m) (95% CI 6,5 – 11,5). Median progression-free survival was 3 m. (95% CI, 2 – 4). Incidence of irAE was 32% (grade 3/4, 17%). IrAE-related discontinuation rate was 13%. Ocurrence of irAE (OR 6.42, 95% CI 2.1 – 19.5, p < 0.002) and decrease in dNLR (vs. increase) at week 3 (OR 3.65, 95% CI 1.14 - 11.69, p=0.034) were associated with response. Hemoglobin (Hb) < 10 mg/dL, LM, decrease in dNLR and ocurrence of irAE were independently associated to OS (Table). Table: 777P
| Variable | Univariate | Multivariate |
| Liver M1 | HR 2.002 (95%CI 0.964 – 4.157) p = 0.062 | HR 2.417 (95%CI 1.062 – 5.499) p = 0.035 |
| Baseline LDH | HR 1.747 (95%CI 0.923 – 3.305) p = 0.086 | HR 1.607 (95%CI 0.816 – 3.167) p = 0.170 |
| Hemoglobin < 10 mg/dL | HR 1.839 (95%CI 1.129 – 2.994) p = 0.014 | HR 1.851 (95% CI 1.165 – 2.941) p = 0.009 |
| Decrease in dNLR at week 3 | HR 0.414 (95% 0.229 – 0.748) p = 0.003 | HR 0.385 (95%CI 0.204 – 0.725) p = 0.003 |
| IrAE Yes | HR 0.401 (95%CI 0.207 – 0.776) p = 0.007 | HR 0.384 (95CI% 0.189 – 0.782) p = 0.008 |
Conclusions
Decrease in dNLR may be an early indicator of therapeutic effect and long-term improved survival in mUC. IrAE and classical factors, as hemoglobin and LM, remained prognostic in our cohort.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
L. Ferrer Mileo: Honoraria (self): Pfizer; Honoraria (self): Kyowa Kirin. M. Orrillo Sarmiento: Honoraria (self): Pfizer; Honoraria (self): BMS. A. Prat: Speaker Bureau/Expert testimony, Research grant/Funding (self), Research grant/Funding (institution): Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Research grant/Funding (institution): Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Amgen; Speaker Bureau/Expert testimony: BMS; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Daiichi Sankyo; Advisory/Consultancy: Puma; Advisory/Consultancy: Oncolytics Biotech; Advisory/Consultancy: MSD; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Speaker Bureau/Expert testimony, Research grant/Funding (self): Nanostring techonologies; Officer/Board of Directors: BIG; Officer/Board of Directors: Solti's Foundation; Officer/Board of Directors: Solti; Officer/Board of Directors: Actitud frente al Cancer Foundation ; Research grant/Funding (self): Sysmex Europa GmbH; Research grant/Funding (self): Medica Scentia Inno. Research, SL; Research grant/Funding (self): Celgene, SLU; Research grant/Funding (self): Astellas Pharma, SA. O. Reig Torras: Speaker Bureau/Expert testimony: BMS; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Ipsen; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer. B. Mellado: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Research grant/Funding (institution): Janssen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Roche; Speaker Bureau/Expert testimony, Leadership role, Research grant/Funding (self): Astellas; Advisory/Consultancy, Research grant/Funding (self): Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Sanofi. All other authors have declared no conflicts of interest.