Utilización, efectividad y toxicidad de los inhibidores de los puntos de control inmunitario, empleados para el tratamiento del cáncer, en condiciones de práctica clínica

Resumen

Immune checkpoints inhibitors (CPI) have triggered a change in treatment strategy for multiple neoplasms. Its use has been associated with durable responses and longer survival although these benefits are restricted to a limited number of treated patients. These treatments can be well tolerated, however, the occurrence of immune-related toxicity entailing serious adverse events (AE) is common, and these may be fatal. These drugs also involve a high economic impact on the National Health System and patients characteristics of those in which they are used in clinical practice conditions differ from those who were included in the clinical trials (CT) that evaluated their use. The objectives of this study are to describe the usage profile of CPI in clinical practice conditions, to analyze their effectiveness within different oncological treatment indications, and to describe which AE are associated with CPI treatment. Secondarily, to define the presence of relevant factors that may influence the response and analyze the impact of these factors on the results obtained in main indications. To this end, it was designed an observational, descriptive and retrospective study that included all patients who started a treatment with an CPI for oncological indications at the Virgen de la Arrixaca University Clinical Hospital up to December 2018. Across different diagnoses, it was performed a descriptive analysis of the demographic and clinical characteristics, other treatments received, as well as specific drug used, achieved response, and appearance of AE. Time to treatment failure, progression-free survival, and overall survival (OS) were analyzed through Kaplan-Meier curves. In order to identify variables as predictors of OS, it was applied The Cox regression model with Benjamini & Hochberg correction. During the study period 262 patients were treated, most of whom were previously diagnosed with non-small cell lung cancer (NSCLC) (61.5%) and advanced melanoma (17.2%). Other minority diagnoses were also included, such as localized melanoma, squamous cell head and neck cancer, renal cell carcinoma, and urothelial carcinoma (UC). Most of patients were treated with anti-PD-1 drugs as monotherapy (92.4%). Among them, there was a high percentage of patients treated in treatment indications subject to reimbursement decision (36.6%). A significant percentage of them showed brain metastases, autoimmune diseases and ECOG 2. Among different treatment indications, OS results obtained were similar to those described in CT that had previously evaluated these drugs, with the exception of first-line NSCLC and advanced-lines treatment of advanced melanoma, in which their results were lower than those described in CT. Among NSCLC patients, the presence of an ECOG value 3, a squamous and undifferentiated histology, and the corticosteroid administration were independently associated with decreased OS, while concomitant radiation therapy, longer response duration and AE were predictive of higher OS. In patients with advanced melanoma, an objective response was the only predictive variable of higher OS. In other indications, it is worth noting the high objective response rate and the OS obtained in patients with UC, as well as the durable response observed in a patient with high-grade glioma and microsatellite instability. In terms of safety, the occurrence of AE was generally similar to that described in CT and real-world data studies, although it is remarkable as infrequent events a case of Fournier's gangrene or another of osteonecrosis of the jaw. However, no direct causality attribution to studied drugs can be made.