Real-World Effectiveness of Calcitonin Gene-Related Peptide-Binding Monoclonal Antibodies for Migraine Prevention: A Systematic Review.

Background: Migraine is a neurological disease with a high incidence. The new anti-calcitonin gene-related peptide monoclonal antibodies (anti-CGRP mAbs) have demonstrated effectiveness in preventing episodic and chronic migraine. Objective: To collect evidence of the real-world effectiveness of anti-CGRP mAbs by assessing outcomes such as reduction in monthly migraine days (MMDs), reduction in monthly headache days (MHDs), and percentage of patients having a 50% reduction in MMDs. Data Sources: The PubMed database was searched for the period from inception to October 20, 2021. Study Selection and Data Extraction: Of interest for this review were studies that evaluated the real-world effectiveness of anti-CGRP mAbs in terms of MMDs and reduction in MHDs. The search terms included "migraine", "monthly migraine days", and various drug names. The data are reported in terms of patients' baseline characteristics and treatment effectiveness. Data Synthesis: A total of 46 studies were evaluated, of which 30 (enrolling a total of 4273 patients across 10 countries) were included in the systematic review. The greatest absolute reduction in MMD was from 20.4 at baseline to 10.7 after 3 months of treatment. After 6 months, the greatest absolute difference was 10, relative to baseline. The largest absolute reduction in MHD at 3 months was from 22 to 8, whereas at 6 months, the greatest absolute reduction in MHD was 13. The treatment could be considered clinically effective (≥ 50% reduction in MMDs) for 41% of patients at 3 months and about 44% of patients at 6 months. Conclusions: Despite substantial variability in baseline values, this review confirmed the effectiveness of anti-CGRP mAbs, which yielded important clinical reductions in both MMDs and MHDs.

Contexte: La migraine est une maladie neurologique à incidence élevée. Le nouvel anticorps monoclonal qui se lie au peptide lié au gène de la calcitonine (AcM anti-CGRP) a démontré son efficacité pour prévenir les migraines épisodiques et chroniques. Objectif: Recueillir des éléments probants concernant l'efficacité réelle des AcM anti-CGRP en évaluant des résultats comme la réduction du nombre de jours de migraine par mois (JMM), la réduction du nombre de jours de céphalées par mois (JCM) ainsi que le pourcentage de patients ayant une réduction de 50 % du nombre de JMM. Sources des données: La base de données PubMed a été utilisée pour mener une recherche pour la période allant du début jusqu'au 20 octobre 2021. Sélection des études et extraction des données: Les auteurs de la revue se sont intéressés aux études qui avaient évalué l'efficacité réelle des AcM anti-CGRP en termes de réduction du nombre de JMM et du nombre de JCM. Les termes de recherche comprenaient « migraine ¼, « jours de migraine par mois ¼ et divers noms de médicaments. Les données sont rapportées en termes de caractéristiques de base des patients et d'efficacité du traitement. Synthèse des données: Au total, 30 des 46 études répondant aux critères d'inclusion (comprenant un total de 4273 patients dans 10 pays) ont été retenues pour la revue systématique. La réduction absolue de JJM la plus importante était de 20,4 (la base de référence) à 10,7 après 3 mois de traitement. Après 6 mois, la différence absolue la plus importante était de 10 par rapport à la base de référence. La réduction absolue de JCM la plus importante à trois mois était de 22 à 8, alors qu'à 6 mois, la réduction absolue de JCM la plus importante était de 13. Le traitement pouvait être considéré comme cliniquement efficace (≥50 % de réduction de JMM) pour 41 % des patients à 3 mois et environ 44 % des patients à 6 mois. Conclusions: Malgré la variabilité importante des valeurs de la base de référence, cet examen confirme l'efficacité des AcM anti-CGRP, qui ont donné lieu à une réduction importante d'un point de vue clinique du nombre de JMM et de JCM.

Is there any place for novel agents in treating biliary tract cancer?

Biliary tract cancer is an uncommon cancer in developed countries. In localized stages, surgery is the cornerstone of treatment with curative purpose. Conversely in advanced stages, chemotherapy with platinum-gemcitabine combination is the standard of care. Biliary tract cancers are a biologically heterogeneous group of malignancies, which perhaps explains the failure of targeted therapies in unselected patient populations to demonstrate benefit in advanced disease, although there are promises in selected populations (e.g. PD1/PD-L1 positive, BRAFV600E-mutated or IDH1-mutant). In view of the limited benefit of second line therapies in metastatic biliary tract cancer, various targeted agents have been tested in progressive disease. Furthermore, several ongoing trials are using next-generation sequencing of multiple genes to identify molecular abnormalities in the tumors of patients with refractory cancers that may potentially be used in pretreated disease (e.g. FGFR or IDH genes). Immunotherapy with immune checkpoint inhibitors may be interesting for patients whose tumors have programmed cell death 1 ligand 1 (PD-L1) overexpression. Ongoing and future trials will further advance our knowledge toward the optimal treatment strategy for the management of biliary tract cancer in its different stages, starting from metastatic and then reaching early stages of disease. We here provided an overview of these novel treatment strategies for advanced biliary tract cancers not amenable of curative treatment modalities.

Continuous-infusion and outpatient setting: A chance for patients, a challenge for hospital pharmacists.

The use of continuous-infusion in outpatient setting could be widely used in oncology and haematology care. Many times the lack of data stability about single drug or admixture of drugs, together with patient education and safety, make difficult the transition from inpatient to outpatient setting. Nowadays, this is a big challenge for hospital pharmacists, who must take into consideration the critical issues related to chemical and physical stability, besides microbiological one, in order to ensure high quality preparations and guarantee the safety and quality of care, to protect patients and their health. The aim of this article is to highlight the critical issues concerning the transition from inpatient to outpatient setting, with particular interest regarding chemotherapy protocols, which require preparation with long-term continuous-infusion.

A systematic review of salvage therapies in refractory metastatic colorectal cancer.

PURPOSE: Established that the only approved agents in previously treated metastatic colorectal cancer (CRC) are trifluoridine/tipiracil and regorafenib, we conducted a systematic review of all the published phase 2-3 trials, with the scope to evaluate the benefit of any later-line regimens in refractory metastatic CRC. METHODS: Phase 2-3 studies that enrolled patients with stage IV disease receiving salvage therapies for refractory CRC were identified using electronic databases (Pubmed, EMBASE, and Cochrane Library). Clinical outcomes were pooled using a point estimates for the weighted values of median overall survival (OS), progression-free survival (PFS), response rate (ORR), stable disease rate (SD), and 6-month and 1-year OS. RESULTS: Overall, 7556 patients were included from 67 studies (n = 70 arms). Overall, the pooled ORR and SD were 15.4% (95% CI 13-18%) and 36.9% (95% CI 33.5-40.6%). Median PFS, 6-month and 1-year OS, and median OS were 3.2 (95% CI 2.9-3.3) months, 65.4% (95% CI 61.9-68.8%), 36% (95% CI 32.3-39.9%) and 8.8 (95% CI 8.3-9.2) months. Overall survival was different in the monochemotherapy, polychemotherapy, chemotherapy + targeted therapy, and targeted therapy alone arms (7.6, 9.5, 10.3, and 7.9 months, respectively, P for difference = 0.01). Median PFS were respectively 2.3, 3.9, 3.8, and 2.6, respectively (P for difference < 0.01). CONCLUSIONS: Overall, combination therapy (polychemotherapy with or without targeted agents) is associated with a higher control of disease and better outcome than approved agents. Treatment, if possible, should be personalized according to the patients' conditions, physician preference and molecular profile of disease.

Pharmacological issues concerning olaparib capsule and tablet formulations in treating ovarian cancer: Are they really the same drug?

Olaparib is a first-in-class PARP inhibitor that has demonstrated efficacy as maintenance therapy in patients with ovarian cancer. It has been approved as a capsule formulation and after the publication of data from SOLO2 study became available also as tablet formulation. Due to different pharmacokinetic properties, these different formulations cannot be considered bioequivalent nor interchangeable. The tablet formulation has improved bioavailability, reducing pill burden and offering a more convenient dosage regimen. Furthermore, olaparib tablet formulation had a manageable tolerability profile if compared to capsule one, with most of adverse events of mild or moderate severity. Under this light, olaparib tablet formulation is a useful maintenance strategy for recurrent, platinum-sensitive ovarian cancer, providing a more convenient dosing option than the capsule formulation.