SAUL, a single-arm study of atezolizumab for chemotherapy-pretreated locally advanced or metastatic carcinoma of the urinary tract: outcomes by key baseline factors, PD-L1 expression and prior platinum therapy.

BACKGROUND: The impact of pretreatment factors on immune checkpoint inhibition in platinum-refractory advanced urothelial cancer (aUC) deserves further evaluation. The aim was to study the association of Bellmunt risk factors, time from last chemotherapy (TFLC), previous therapy and PD-L1 expression with atezolizumab efficacy in platinum-refractory aUC. PATIENTS AND METHODS: This was a post-hoc analysis of patients who had received prior cisplatin or carboplatin in the prospective, single-arm, phase IIIb SAUL study (NCT02928406). Patients were treated with 3-weekly atezolizumab 1200 mg intravenously. The primary outcome was overall survival (OS). Relationships were analysed using Cox regression and long-rank test. RESULTS: Of 997 patients in SAUL, 969 were eligible for this analysis. The number of Bellmunt risk factors was associated with OS (P < 0.001); median OS (mOS) for 0, 1 and 2-3 risk factors was 17.9, 8.9 and 3.3 months, respectively. Significant associations were also observed between OS and TFLC (P < 0.001), programmed death-ligand 1 (PD-L1) expression (P = 0.002), and prior perioperative chemotherapy (P = 0.013); mOS was 6.97 versus 11.63 months for TFLC ≤6 versus >6 months, 7.75 versus 11.6 months for PD-L1 expression on <1% of tumour-infiltrating immune cells (ICs) (IC0)/expression on 1% to <5% of tumour-infiltrating ICs (IC1) versus expression on ≥5% of tumour-infiltrating ICs (IC2/3) and 10.2 versus 7.8 months for prior versus no prior perioperative chemotherapy, respectively. The type of platinum compound and number of previous treatment lines were not associated with outcomes. CONCLUSIONS: Post-platinum atezolizumab is active in aUC, irrespective of previous platinum compound and lines of therapy. Bellmunt risk stratification, PD-L1 expression, TFLC and perioperative chemotherapy were identified as prognostic factors for OS with second-line atezolizumab, indicating the need for novel prognostic signatures for immunotherapy-treated patients with aUC.

Axitinib as a third or further line of treatment in renal cancer: a single institution experience.

BACKGROUND: Kidney cancer is a lethal neoplasm that affects several thousands of people every year. Renal cell carcinoma (RCC) is the most common histologic type. Recent developments in the therapeutic approach include antiangiogenic targeted approaches and Immunotherapy. Thus, the therapeutic algorithm of RCC patients and the survival outcomes have changed dramatically. METHODS: Herein we present a retrospective study of the patients treated in our Department with an antiangiogenic agent -Axitinib, a tyrosine kinase inhibitor- as a third or further line treatment. Statistical analysis was performed with SPSS, including the available clinicopathological data of the patients included. RESULTS: Axitinib was found to be active in patients who received this treatment beyond second line. The toxicity profile of this regimen did not reveal any unknown adverse events. CONCLUSIONS: Our real world data reflect that axitinib is a safe and effective option, even beyond the second line.

Increased prevalence of Chlamydophila pneumoniae but not Epstein-Barr antibodies in essential hypertensives.

Conflicting data exist regarding the relationship between Chlamydophila pneunoniae (C. pneumoniae) and hypertension. In this study, both C. pneumoniae IgG and IgA titres and Epstein-Barr virus antibody levels were measured in 146 sustained hypertensives defined by 24 h ambulatory blood pressure monitoring (ABPM) and 54 normotensives. C. pneumoniae antibodies were measured by microimmunofluorescence test. IgG > or = 80 and IgA > or = 40 were defined as elevated antibody titres. Epstein-Barr antibodies were measured in order to investigate whether a possible association exists between hypertension and other, similarly widespread in the general population, intracellular microorganisms. All participants underwent casual blood pressure (BP) readings and 24 h ABPM. Subjects having mean 24 h systolic/diastolic ambulatory BP>125/80 mmHg, with or without antihypertensive medication were defined as hypertensives. Controls were free of any history or clinical evidence of hypertension, cardiovascular or pulmonary disease. Of the total participants, 77 hypertensives (52.7%) and 10 normotensives (18.5%) had IgA titres > or = 40 (crosstabs P < 0.000), whereas 76 hypertensives (52.1%) and 15 normotensives (27.8%) had IgG titres > or = 80, (crosstabs P < 0.002). No difference was found in Epstein-Barr antibodies, between hypertensives and normotensives. In conclusion, C. pneumoniae, but not Epstein-Barr, antibody levels were found significantly higher in sustained hypertensives, suggesting high frequency of chronic C. pneumoniae, infections in this specific group of patients.