Real-world data of atezolizumab in patients with previously treated locally advanced or metastatic urothelial bladder cancer.

BACKGROUND: Clinical trials of atezolizumab for locally advanced or metastatic urothelial bladder cancer (mUBC) report controversial efficacy data. Furthermore, real-world evidence about this use is limited. AIM: We aimed to evaluate the effectiveness of atezolizumab in a real-world population with mUBC, to explore effectiveness with regard to selected poor prognostic criteria such as performance status by Eastern Oncology Cooperative Group (ECOG), hemoglobin levels and liver metastases, and to determine the safety profile of atezolizumab. METHOD: Multicenter, retrospective real-world study including previously treated mUBC patients who received atezolizumab. The primary endpoint was overall survival (OS). Additionally, progression-free survival (PFS), best response reached and safety data were analyzed. A descriptive analysis was performed, while OS and PFS were estimated by Kaplan-Meier method. RESULTS: A total of 185 patients (84.9% men, median age 69 years) were included. Median PFS was 4.8 months [95% confidence interval (CI) 3.6-6.0], and median OS was 20.0 months (95% CI 11.8-28.5), with an objective response rate of 28.1%. OS was higher for patients with ECOG 0-1 versus 2-3 [24.5 months (95% CI 14.5-34.6) vs. 5.2 (95% CI 4.4-6.0), p = 0.004]; and for patients without liver metastases [25.4 months (95% CI 16.2-34.6) vs. 6.4 months (95% CI 4.0-8.1), p = 0.006]. Regarding hemoglobin levels, no survival differences were detected. Adverse events were registered in 55.1% of patients. CONCLUSION: In a real-world population with previously treated mUBC, atezolizumab seems to provide clinically relevant benefit, which is even higher for patients with ECOG 0-1 and without liver metastases, with an acceptable safety profile.

Bevacizumab and aflibercept in second-line metastatic colorectal cancer: 12 years of experience.

PURPOSE: To evaluate and compare the efficacy and safety of bevacizumab and aflibercept in second-line treatment in metastatic colorectal cancer (mCRC) in real-life clinical practice. METHODS: Retrospective observational study of patients treated with second-line bevacizumab (BFIR) and aflibercept (AFIR) in mCRC, associated with a FOLFIRI scheme, in the last 12 years (January 2009-January 2021) in a tertiary hospital. Patients with prior oxaliplatin-based treatment were included. VARIABLES MEASURED: previous chemotherapy, treatment time (TT), progression-free survival (PFS), overall survival (OS). To assess toxicity, adverse effects that caused delay in cycle administration were recorded. The lost cycles/month of treatment (CP/MT) were also calculated. RESULTS: Eighty-four patients [40 (47.6%) AFIR and 44 (52.4%) BFIR]. Average age: 60.2 ± 10.7 years. In 79.8% the previous scheme was FOLFOX type. Efficacy of AFIR vs BFIR: median HR of TT (95% CI) = 0.816 (0.527-1.266); p = 0.365, PFS HR (95% CI) = 0.674 (0.389-1.117); p = 0.159, OS HR (95% CI) = 0.566 (0.342-0.936); p = 0.026. The main reason for the delay in administration was neutropenia (28.7% AFIR vs 24.7% BFIR), and the greatest difference found was thrombopenia (13.9% AFIR vs 2.5% BFIR), without observing large differences between the rest of adverse reactions. Mean CP/MT: 0.49 ± 0.46 cycles with AFIR and 0.33 ± 0.27 with BFIR; p = 0.046. CONCLUSION: Although no statistically significant differences have been found in TT or PFS, it would be more advisable to use BFIR scheme due to its better results in OS and toxicity profile.

RESUMEN: OBJETIVO: Evaluar y comparar la eficacia y seguridad de bevacizumab y aflibercept en segunda línea de tratamiento en el cáncer colorrectal metastásico (CCRm) en la práctica clínica real. MéTODOS: Estudio observacional retrospectivo de los pacientes tratados con bevacizumab (BFIR) y aflibercept (AFIR) en segunda línea en CCRm, asociado a un esquema FOLFIRI, en los últimos 12 años (septiembre 2009-enero 2021) en un hospital de tercer nivel. Se incluyeron pacientes con tratamiento previo basado en oxaliplatino. Variables medidas: esquema previo, tiempo de tratamiento (TT), supervivencia libre de progresión (SLP), supervivencia global (SG). Para valorar toxicidad, se registraron los efectos adversos que provocaron retraso en la administración del ciclo. También se calcularon los ciclos perdidos/mes de tratamiento (CP/MT). RESULTADOS: 84 pacientes [40 (47,6%) AFIR y 44 (52,4%) BFIR]. Media de edad: 60,2 ± 10,7 años. En el 79,8% el esquema previo fue tipo FOLFOX. Eficacia de AFIR vs BFIR: HR de mediana de TT (IC95%) = 0,816 (0,527­1,266); p = 0,365, HR de SLP (IC95%) = 0,674 (0,389­1,117); p = 0,159, HR de SG (IC95%) = 0,566 (0,342­0,936); p = 0,026. El principal motivo de retraso en la administración fue neutropenia (28,7% AFIR vs 24,7% BFIR), y el que más diferencia hubo entre ambos la trombopenia (13,9% AFIR vs 2,5% BFIR), sin observarse grandes diferencias entre el resto de reacciones adversas. Media de CP/MT: 0,49 ± 0,46 ciclos con AFIR y 0,33 ± 0,27 con BFIR; p = 0,046. CONCLUSIONES: Aunque no se han encontrado diferencias estadísticamente significativas en TT ni en SLP, sería más recomendable utilizar el esquema BFIR por sus mejores resultados en SG y perfil de toxicidad.

Early use of tocilizumab in patients with severe pneumonia secondary to severe acute respiratory syndrome coronavirus 2 infection and poor prognostic criteria: Impact on mortality rate and intensive care unit admission.

ABSTRACT: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2, keeps spreading globally. Evidence suggests that a subgroup of patients with severe symptomatology might have cytokine storms, which increases mortality. The use of interleukin-6 (IL-6) inhibitors may help in controlling the pathological immune response to the virus. Tocilizumab, a monoclonal antibody against IL-6, stands as an optional treatment for COVID-19 patients presenting this inflammatory hyper-response.We conducted a retrospective, observational, cohort study including 50 patients affected by COVID-19 with severe pneumonia and poor prognosis criteria, who have also undergone standard treatment; 36 of these patients additionally received tocilizumab in an early stage. The need for intensive care unit (ICU) admission, mortality, recovery of respiratory function, and improvement of biochemical and hematological parameters were compared between cohorts.Most patients were men, non-smokers and the most frequently reported comorbidities were hypertension and diabetes. Recurrent symptoms were fever, cough, and dyspnoea. 54.8% of patients from the tocilizumab group needed intubation, while in the control group 85.7% needed it. Treatment with tocilizumab significatively increased IL-6 levels, (554.45; CI 95% 186.69, 1032.93; P < .05) while C-reactive protein mean levels were reduced (-108.19; CI 95% -140.15, -75.33; P < .05), but no significant difference was found between cohorts. In comparison with the controls, tocilizumab reduced mortality (25.0% vs 42.9%, P = .021) and the number of ICU admissions (63.9% vs 100.0%, P = .021). 44.1% of patients treated with tocilizumab showed favorable radiological evolution, when compared with 15.4% of patients from the control group.Tocilizumab may improve clinical symptoms and mitigate deterioration observed in severe COVID-19 patients, and could be considered as an effective therapeutic option in subjects experiencing a significant inflammatory response to the disease.

A multicentre observational study of the effectiveness, safety and economic impact of nivolumab on non-small-cell lung cancer in real clinical practice.

Background Immunotherapy has become a standard treatment for lung cancer; however, the high cost makes it necessary to assess health outcomes. Objective The aim of this study was to evaluate the effectiveness, safety and economic cost of nivolumab in real-world clinical practice. Setting Fifteen regional and academic hospitals from Spain participated in this study. Methods This study was a retrospective, multicentre and observational study involving patients who experienced progression after first-line therapy for non-small-cell lung cancer and were treated with nivolumab between January 2016 and July 2017. Effectiveness and safety were evaluated by the oncologist, and the data from the electronic clinical records of the patients were collected by the research team. Economic cost was calculated using the cost of acquiring nivolumab for the public health system. Main outcome measures Effectiveness variables were overall survival (OS) and progression-free survival (PFS). The safety variable was the incidence of adverse events (AEs), and the cost per life-year gained (LYG) was the economic variable. Results A total of 221 patients were enrolled (83.7% men). The mean age was 64.5 years, and 84.6% of the patients had an Eastern Cooperative Oncology Group (ECOG) performance-status score of 0-1. Squamous tumours accounted for 59.7% of the total, and 78.7% of the patients presented a time since platinum therapy (TPT) > 6 months. The mean nivolumab dose was 216 mg (SD 211), and the treatment duration was 7.0 months (95% CI 5.8-8.1). The median PFS was 5.3 months (95% CI 3.2-7.3), and OS was 9.7 months (95% CI 7.6-11.8). The median PFS and OS values were statistically significantly superior for patients with an ECOG score of 0-1 and for patients with a TPT > 6 months. The median OS was also statistically significantly superior for patients with non-squamous histology. Regarding safety, 71% of the patients presented AEs of any grade, and in 18.6%, the nivolumab treatment had to be delayed or discontinued. The cost of nivolumab per patient was €19,910.00 (SD 19,369), and the cost per LYG was €110,026.00 (€77,557.00-€231,171.00). Conclusions This study confirms that the efficacy and safety of nivolumab treatment in a real population are comparable to the results obtained in clinical trials. A greater clinical benefit of nivolumab therapy was observed in patients with an ECOG score of 0-1, a TPT > 6 months or non-squamous histology. Despite the benefit observed, the cost per LYG is above the threshold of efficiency established by public health institutes.