Clinical, molecular, and immune correlates of the Immunotherapy Response Score in patients with advanced urothelial carcinoma under atezolizumab monotherapy: analysis of the phase II IMvigor210 trial.

BACKGROUND: In the advanced urothelial carcinoma (aUC) scenario there are no consistent immune checkpoint blockade predictive biomarkers. Recently a novel pan-tumor molecular tissue-based biomarker, the Immunotherapy Response Score (IRS), has been proposed. We conducted a retrospective study to validate the prognostic/predictive utility of the IRS in patients with aUC under atezolizumab monotherapy and to characterize its underlying molecular/immune features in the context of the IMvigor210 phase II trial. PATIENTS AND METHODS: This is a post hoc pooled analysis of 261 patients with available clinical, molecular, and immune tumor data treated with atezolizumab monotherapy in the IMvigor210 phase II clinical trial. Efficacy endpoints were overall survival (OS), disease control rate (DCR), and overall response rate (ORR). Survival estimates were calculated by the Kaplan-Meier method, and groups were compared with the log-rank test. The Cox proportional hazards regression model was used to evaluate factors independently associated with OS. Factors associated with disease control (DC) and response were tested with logistic regression in univariable and multivariable analyses. Comparisons between patient and disease characteristics were carried out using chi-square or Fisher's exact tests. All P values were two-sided, and those <0.05 were considered statistically significant. RESULTS: High IRS was significantly associated with a better OS in univariable [hazard ratio (HR) = 0.49, P < 0.001] and multivariable (HR = 0.60, P = 0.018) analyses. DCR and ORR were significantly higher among high IRS patients (DCR for high IRS versus low IRS patients: 57% versus 32%, P < 0.001; ORR: 42% versus 10%, P < 0.001). High IRS patients presented a higher probability of DC and response in univariable [DC: odds ratio (OR) = 2.72, P < 0.001; response: OR = 3.92, P < 0.001] and multivariable (DC: OR = 2.72, P < 0.001; response: OR = 3.92, P < 0.001) analyses. CONCLUSIONS: This study validates IRS as a strong independent prognostic and predictive biomarker for OS and DC/response in patients with aUC treated with atezolizumab monotherapy in the IMvigor210 phase II clinical trial.

Aspectos éticos de la interacción de las ciencias de la vida y las ciencias de la información / Ethical Aspects of the Interaction between Life Sciences and Information Sciences

Se analiza el desarrollo de las Ciencias de la Información y de la Genética Humana en las últimas décadas; así como la creciente importancia de los aspectos éticos en esta interrelación. El desarrollo de la ingeniería genética y las nuevas tecnologías de la información a finales del siglo XX, condicionaron el surgimiento de una disciplina que generó vínculos indisolubles entre la Informática y las Ciencias Biológicas: la Bioinformática. La aplicación del conocimiento genómico en beneficio de todos los seres humanos es un derecho inalienable cuyos principios básicos son: la privacidad de la información genética, la atención equitativa, la igualdad de oportunidades para todos los ciudadanos con o sin una genética favorable y el respeto a la autonomía, entre otros.

An analysis is made on the development of information sciences and human genetics in the last decades, as well as the increasing importance of the ethical aspects of this interrelation. The development of genetic engineering and the new information technologies in the late XX century, conditioned the origin of a discipline that generated solid bonds between Informatics and Biologic Sciences: Bioinformatics. The application of genomic knowledge for the benefit of mankind is an inalienable right whose basic principles are: the privacy of genetic information, unbiased action, and equality of opportunities for all citizens with or without favourable genetics, as well as respect to autonomy, among others.