Real-world effectiveness of ribociclib in metastatic breast cancer patients: Does dose affect survival?

Introduction: Real-world data are critical to demonstrate the reproducibility of evidence and external generalizability of randomized clinical trials. The purpose of this study was to assess real-world security profile and management of adverse events (AEs) presented with ribociclib for the treatment of HR + /HER2- metastatic breast cancer (MBC). Our secondary objective was to provide real-world effectiveness of this treatment (measured with progression-free survival (PFS)) and to confirm the hypothesis that dose reductions are not related with disease progression. Material and methods: Observational retrospective study evaluating all females with MBC treated with ribociclib. Study period: January 2017 to September 2019. Follow-up was done until November 2021. Response was assessed through the PFS according to RECIST1.1 and National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) was used to classify AEs. Results: The most common AE was any grade neutropenia, documented in 37 of 53 patients (69.8%) during the course of treatment. By the end of the follow-up period, overall median PFS with ribociclib therapy was 27.3 months (95% confidence interval (CI) 20.8-71.8 months). In total, 50 patients (94.4%) initiated ribociclib at 600 mg dose, 28 patients (58%) required dose reductions. PFS of patients receiving ribociclib as first-line treatment was 28 (95% CI 15-41 months). Conclusions: Our results from patients treated in real-world clinical settings indicate that ribociclib is safe and their AEs are manageable with active monitoring, temporal suspension of treatment and dose reduction. Furthermore, our results indicate that dose reduction of ribociclib is not associated with a loss of efficacy.

Effectiveness and Safety of Palbociclib plus Endocrine Therapy in Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: Real-World Results.

BACKGROUND: Real-world data are critical to demonstrate the reproducibility of evidence and the external generalizability of randomized clinical trials. Palbociclib is an oral small-molecule inhibitor of cyclin-dependent kinases 4/6 that has been shown to improve progression-free survival when combined with letrozole or fulvestrant in phase 3 clinical trials. OBJECTIVE: To evaluate real-world outcomes in patients with metastatic breast cancer who received palbociclib in combination with endocrine therapy in routine clinical practice. METHODS: In this retrospective observational multicentre study, data were evaluated for all women with metastatic breast cancer who were treated with palbociclib from April 2017 to September 2019. Treatment response was assessed through progression-free survival according to the Response Evaluation Criteria in Solid Tumors, version 1.1. RESULTS: Fifty-three patients were included in the study, with median age 57 years (range 31-87 years). For all patients treated with palbociclib, median progression-free survival by the end of the study period was 14.4 months (95% confidence interval [CI] 6.2-22.2 months). Twenty-three women who received palbociclib as a first-line treatment did not experience progression-free survival; for these patients, the median treatment duration was 12.1 months (95% CI 1.4-28.0 months). For the 23 patients who received palbociclib as second-line therapy for metastatic breast cancer, median progression-free survival was 13.3 months (95% CI 4.1-22.4 months). Among the 7 women who received palbociclib as third-line therapy, median progression-free survival was 6.0 months (95% CI 0.9-11.1 months). The most common adverse events were hematologic, with grade 3 or 4 neutropenia occurring in 20 (38%) of the 53 patients. CONCLUSIONS: This study provides data from a real-world setting that match the results of previous studies in terms of effectiveness (i.e., progression-free survival) when palbociclib plus endocrine therapy was used as second- or third-line treatment. Palbociclib had appropriate tolerability and a profile of easily manageable adverse effects, with none of the patients suspending their treatment because of toxic effects.

CONTEXTE: Les données du monde réel sont essentielles pour démontrer la reproductibilité des éléments probants et la « généralisabilité ¼ externe des essais cliniques randomisés. Il a été démontré qu'en association avec le létrozole ou le fulvestrant dans les essais cliniques de phase 3, le palbociclib (un inhibiteur oral à petite molécule des kinases dépendantes des cyclines 4/6) améliorait la survie sans progression. OBJECTIF: Évaluer les résultats réels des patientes atteintes d'un cancer du sein métastatique qui ont reçu du palbociclib en association avec un traitement endocrinien dans le cadre d'une pratique clinique de routine. MÉTHODES: Dans cette étude observationnelle rétrospective multicentrique, les données ont été évaluées pour toutes les femmes atteintes d'un cancer du sein métastatique et qui ont été traitées avec du palbociclib d'avril 2017 à septembre 2019. La réponse au traitement a été évaluée par la survie sans progression au moyen des critères RECIST d'évaluation de la réponse des tumeurs solides, version 1.1. RÉSULTATS: Cinquante-trois patientes (âge médian : 57 ans; extrêmes 31­87 ans) ont été incluses dans l'étude. Pour toutes les patientes traitées avec le palbociclib, la survie moyenne sans progression à la fin de la période d'étude était de 14,4 mois (intervalle de confiance à 95 % [IC] 6,2­22,2 mois). Vingt-trois femmes ayant reçu du palbociclib en guise de traitement de première ligne n'ont pas connu de survie sans progression; pour ces patientes, la durée moyenne du traitement était de 12,1 mois (IC à 95 % 1,4­28 mois). Pour les 23 patientes ayant reçu le palbociclib en guise de traitement de deuxième ligne pour le cancer du sein métastatique, la survie moyenne sans progression était de 13,3 mois (IC à 95 % 4,1­22,4 mois). Parmi les 7 femmes ayant reçu le palbociclib en guise de traitement de troisième ligne, la survie moyenne sans progression était de 6,0 mois (IC à 95 % 0,9­11,1 mois). Les effets indésirables les plus fréquents étaient d'ordre hématologique, avec une neutropénie de grade 3 ou 4 survenant chez 20 (38 %) des 53 patientes. CONCLUSIONS: Cette étude fournit des données provenant d'un contexte réel. Elles correspondent aux résultats d'études précédentes en termes d'efficacité (c'est-à-dire « survie sans progression ¼) lorsque le palbociclib, associé à un traitement endocrinien, était utilisé comme traitement de deuxième ou de troisième ligne. Le seuil de tolérance du palbociclib est approprié et son profil d'effets indésirables est facilement gérable : aucune des patientes n'a en effet suspendu son traitement en raison d'effets toxiques.

Diagnóstico al alta y causas de mortalidad de pacientes VIH+ ingresados en un hospital de tercer nivel / Hospital admission and mortality causes of HIV patients in a third level hospital

INTRODUCCIÓN: El objetivo del presente trabajo es describir el perfil de los pacientes VIH que ingresan en un hospital de tercer nivel así como analizar las causas de ingreso hospitalario y de mortalidad durante el mismo. MATERIAL Y MÉTODOS: Estudio observacional, retrospectivo llevado a cabo en un Hospital de tercer nivel. Criterios de inclusión: Pacientes ≥18 años con prescripción de tratamiento antirretroviral (TAR) y diagnóstico de VIH conocido o descubierto durante el ingreso.como motivo de ingreso hospitalario se utilizó el diagnóstico al alta de cada paciente. Se recogieron variables clínicas, analíticas así como las causas de exitus. RESULTADOS: En el periodo de estudio ingresaron un total de 162 pacientes VIH. Cumplieron los criterios de inclusión 128, de los cuales 8 fueron diagnosticados como VIH de novo. Un 79,7% fueron varones; edad 50,29+/-9,81 años. El principal diagnóstico al alta (38,3%) fueron ciertas enfermedades infecciosas y parasitarias (Clasificación CIE-10) y dentro de esta clasificación, las infecciones directamente relacionadas con el VIH fueron las mayoritarias (24,1%). Las tasas de mortalidad de los pacientes VIH ≥18 años que ingresaron en el Hospital (años 2016 y 2017) fue del 13,52%. Las causas de muerte más frecuentes fueron ciertas enfermedades infecciosas y parasitarias seguidas de neoplasias. CONCLUSIONES: Nuestros resultados enfatizan la necesidad de seguir reforzando el diagnóstico precoz de VIH así como la profilaxis primaria de Pneumocysitis jirovecii en los pacientes VIH. Insistir en la adherencia al TAR desde las consultas de seguimiento de especialista en enfermedades infecciosas y en las consultas de atención farmacéutica, concienciar a los clínicos en la prescripción del TAR durante el ingreso hospitalario así como solicitar analíticas de CV y linfocitos CD4 a todos los pacientes VIH ingresados en el Hospital

INTRODUCTION: The aim of this study is to describe the HIV population admitted to a tertiary level hospital and analyze hospital admission and mortality causes during hospitalization. MATERIAL AND METHODS: Observational, retrospective study carried out in a third level Hospital. Inclusion criteria: Patients ≥18 years with a prescription of ART and diagnosis of HIV known or discovered during admission. It was accepted hospital ward discharge diagnose as hospitalization causes. Clinical, analytical outcomes as well as causes of mortality were collected. RESULTS: Among 162 hospitalized HIV infected, 128 met the inclusion criteria, 8 of those were diagnosed as naive HIV patients.79.7% were male; Age 50.29 +/- 9.81 years. The main reasons for hospital admissions (38.3%) were certain infectious and parasitic diseases (ICD-10 Classification) and more specifically human immunodeficiency virus [HIV] disease represented 24,1% of whole hospitalizations. Mortality rates of ≥18 years HIV patients that were admitted to hospital during 2016-2017 were the 13.52%. The main causes of death were certain infectious and parasitic diseases followed by malignancies. CONCLUSIONS: Our results emphasize the need of intensifying the HIV early diagnosis as well as Pneumocystis jirovecii primary prophylaxis. Insist on ART adherence from infectology follow-up appointment and pharmacy care consultations, educate clinics on ART treatment prescription during hospital admission as well as requesting viral and CD4 lymphocytes loads to every HIV admitted patients