Hospital San Pedro de Alcántara

<h3>Background and Importance</h3> Abemaciclib is a CDK4/6 inhibitor (CDKi) indicated for treatment of HER2 negative (HER2-) advanced luminal breast cancer (ALBC). Its safety profile is decisive in clinical practice. <h3>Aim and Objectives</h3> To analyse abemaciclib’s safety and its impact on treatment course of patients with HER2- ALBC. <h3>Material and Methods</h3> Design: multicentric, observational, descriptive and retrospective study. Inclusion criteria: Cáceres and Badajoz patients who started abemaciclib during 1/7/17–31/3/24. Exclusion criteria: early–stage patients starting adjuvant treatment. Follow–up period: from 1/7/17 to 31/3/25. Data: age at abemaciclib beginning, medical history, adverse events (AEs) classified per Common Terminology Criteria for AE (CTCAE), treatment suspensions, dose reductions and switches to another CDKi. Data collection and processing: electronic health record, FarmaTools and Excel . <h3>Results</h3> 64 patients met the inclusion criteria and finally 30 women resulted after exclusion criteria applied. Median age at beginning: 59 years (interquartile range IQR:55.25–71.5). Comorbidities included hypertension (10), dyslipidemia (10), smoking (10), cardiovascular events (4), diabetes (4), other neoplasms (6), and one immune–mediated disease. Recorded AEs by grade (table 1): Implications of these AEs during the course of therapy: o Dose reductions due to toxicity: 33.3% of cases. o Temporary suspensions due to toxicity: 43.3% of cases. o Permanent suspensions due to toxicity: 23.3% of cases, of which 85.7% switched to another CDKi. <h3>Conclusion and Relevance</h3> The most common AEs of any grade was diarrhoea, followed by asthenia/fatigue. Serious but uncommon AEs included PTE, neutropenia, pneumonitis. These AEs meant that more than 40% of patients had to temporarily suspend treatment, in more than 30% the dose was reduced, and more than 20% permanently suspended treatment to switch to another CDKi. <h3>Conflict of Interest</h3> No conflict of interest

Despite the well-established benefits of physical activity for breast cancer survivors (BCS), adherence to exercise guidelines remains strikingly low (5–30%), highlighting the urgent need to identify limitations and employ motivational frameworks to increase intervention effectiveness. This cross-sectional study examined the associations among exercise motivation, physical activity levels, quality of life (QoL), and healthy lifestyle behaviours in BCS, using Self-Determination Theory (SDT) as the theoretical foundation. Thirty-five BCS participated, with a mean age of 59.97 ± 10.80 years. The results showed that the highest scores were recorded in identified regulation, social well-being, sleep habits, and dietary habits, while the lowest were found for physical activity participation and additional concerns. Significant correlations emerged among self-determined motivation, basic psychological needs, lifestyle habits, and QoL, providing valuable insights into their interrelationships. These findings highlight the importance of designing and implementing motivational programs that promote adherence to physical exercise and improve the QoL in this population.

Cytisinicline has proven to be an effective, efficient, and safe molecule in smoking cessation. However, the established 25-day regimen could be insufficient in a high percentage of smokers, so it is necessary to study maintained therapies of this drug. This study aims to compare the efficacy of the cytisinicline regimen used in routine clinical practice versus 2 maintained regimens of 50 and 75 days, respectively. In addition, the safety and economic impact of each regime will be determined. A prospective, multicenter, open-label, controlled, parallel, phase IV clinical trial of 402 smoker patients prepared to quit smoking. The study was conducted in 10 hospitals in Spain. A control group is compared to 2 intervention groups in which the duration of the drug is increased without increasing its dose, administering half and all, respectively, of an additional marketed container that includes 100 tablets. Thus, participants will be randomized to three groups in a 1:1:1 ratio to receive cytisinicline: (1) a control group treated with cytisinicline according to the usual clinical guidelines and product information (25 days); (2) a group with a 50-day cytisinicline regimen (an additional 25 days at a dose of 1.5 mg every 12 hours), seeking to increase its efficacy while minimally impacting adherence; and (3) a group with a 75-day regimen (an additional 50 days at a dose of 1.5 mg every 12 hours), attempting to increase its efficacy, although the longer duration of the drug may threaten adherence. Efficacy in the 3 arms will be analyzed through sustained abstinence at 6 and 12 months, point abstinence rate assessed every 7 days, and abstinence rate from Day 25 to Day 50 and from Day 25 to Day 75 in the 3 study arms. (1) The variation in withdrawal and craving symptoms in the 3 groups, (2) safety through the percentage of adverse events in the 3 treatment arms, and (3) economic impact by evaluating the cost-effectiveness and cost-utility ratios of the 2 prolonged regimens versus the usual clinical cytisinicline regimen. To calculate the differences between the 3 groups for each outcome variable, a univariate analysis will be performed. Statistically significant variables will be included in a multivariate model. Recruitment for the trial and patient enrollment were completed in November 2026. Follow-up of all participants will extend to December 2027. In conclusion, this study evaluates the optimization of cytisinicline in daily clinical practice, increasing the benefits of its pharmaceutical properties without affecting patient safety. All of this will improve the effectiveness of smoking cessation by reducing the number of smokers, which implies lower morbidity and mortality and lower costs associated with smoking. European Clinical Trials Register 2024-518936-36-00; https://euclinicaltrials.eu/ctis-public/view/2024-518936-36-00. PRR1-10.2196/76815.

In the context of advanced BRAF-mutant melanoma, the treatment landscape has undergone a paradigm shift due to the impact of immune checkpoint inhibitors and BRAF/MEK inhibitors. This article presents three clinically illustrative melanoma cases that served as focal points for in-depth discussions during 12 expert meetings held across Spain. These include a treatment-naïve metastatic melanoma patient, a patient experiencing a recurrence while on anti-PD-1 adjuvant therapy, and a third patient whose melanoma relapsed ≥6 months after the end of adjuvant therapy. The discussions revolved around optimal treatment sequencing, emphasizing the challenges and alternatives discussed in each scenario. The common view aligned towards a nuanced approach that involves navigating the complexities of treatment choices. The conclusions underscore the need for personalized therapeutic strategies and highlight the ongoing challenge of refining real-life evidence-based algorithms for the management of metastatic BRAF-mutant melanoma.

Brazil is a country with the greatest biodiversity inthe world,but much of it is still largely unexplored. Trigynaeaaxilliflora (Annonaceae) is a Brazilian plant speciesthat has not been previously studied. This research aimed to characterizethe chemical constituents and evaluate the biological activities ofthe extract, fractions and isolated compounds. Xylopine, a major compoundisolated from this extract, is an aporphine alkaloid and a chemotaxonomicmarker of this family, whose structure was confirmed by 1H/13C NMR and HRESIMS. HPLC-UV-ESI-qTOF dereplicationindicated that xylopine and seven other aporphine alkaloids were presentin the crude extract. A solvent washing procedure allowed the recoveryof 138 mg of xylopine, with a yield of 13.8% (138 mg/g crude extract)and 95% purity by HPLC-DAD. Cytotoxicity by the MTT assay showed thatxylopine was active against MG-63 osteosarcoma cells (IC50 = 5.5 μg/mL), with a selectivity index (SI = 0.63) indicatinga favorable selectivity compared to doxorubicin (SI = 0.22). Antibacterialassays demonstrated the inhibition of Staphylococcusaureus and Escherichia coli by the ethanolic extract and chloroform fraction (MIC 125–500μg/mL), as well as by xylopine (MIC 62.5 μg/mL for S. aureus and 31.2 μg/mL for E. coli). To evaluate antinociceptive activity, theformalin test was used, and both the ethanolic extract and xylopinesignificantly reduced nociceptive behavior during the inflammatoryphase from 123.8 ± 13.7 s (100%) to 71.3 ± 10.2 s (57.5%)and 1.3 ± 0.4 s (1%), respectively, at doses of 30 mg/kg. Insilico pharmacokinetic analysis using SwissADME predicted favorabledrug-likeness and oral bioavailability for xylopine, supporting itspotential as a drug candidate. This study presents the first reporton the chemical profile and bioactivities of T. axilliflora, suggesting it as a possible natural source of xylopine. This findinghighlights the importance of phytochemical and pharmacological researchin understanding Brazil’s understudied flora.

PURPOSEQuizartinib, an oral, selective, second-generation, type-II FMS-like tyrosine kinase 3 (FLT3) inhibitor with high binding affinity to internal tandem duplication (ITD) and wild-type (WT) FLT3, has shown early clinical activity as monotherapy in patients with relapsed/refractory FLT3-ITD–negative AML. The phase III QuANTUM-First trial showed that quizartinib significantly prolonged survival versus placebo when added to standard chemotherapy, followed by single-agent maintenance, in patients with newly diagnosed (ND) FLT3-ITD–positive AML. We investigated the safety and efficacy of quizartinib in patients with ND FLT3-ITD–negative AML.METHODSThe phase II, randomized, double-blind, placebo-controlled QUIWI trial enrolled patients age 18-70 years with ND FLT3-ITD–negative (mutant-to-WT allelic ratio <0.03) AML. Patients were randomly assigned 2:1 to receive standard induction and consolidation chemotherapy combined with either quizartinib 60 mg once daily or placebo, followed by single-agent maintenance with quizartinib or placebo. The primary end point was event-free survival (EFS). Secondary end points included overall survival (OS) and safety.RESULTSOverall, 273 patients were randomly assigned to quizartinib (n = 180) or placebo (n = 93). At data cutoff, median EFS was 20.4 months and 9.9 months in the quizartinib and placebo arms, respectively (P = .046). Median OS was not reached and 29.3 months in the quizartinib and placebo arms, respectively (P = .012); 3-year OS rates were 60.8% and 45.7%. The most frequently reported adverse events (any grade) were fever, rash, diarrhea, and mucositis.CONCLUSIONThe addition of quizartinib to standard chemotherapy was associated with significantly longer EFS and OS than placebo in patients with ND FLT3-ITD–negative AML.

Most patients with BRAF-mutant melanoma eventually develop resistance to BRAF/MEK inhibitors (BRAF/MEKi) and immune-checkpoint blockade. Emerging evidence from retrospective cohorts indicates promising activity from re-exposure to BRAF/MEKi after a treatment-free interval of targeted therapy (TT), probably due to tumor regression and proliferation of sensitive clones. However, there is limited prospective evidence on this approach. GEM1801 is a prospective observational study by the Spanish Melanoma Group (GEM), including 1123 patients treated at 37 centers. We conducted a descriptive analysis of baseline characteristics, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) for the 24 patients who received a second course of BRAF/MEKi, either as retreatment (after relapse following prior adjuvant TT) or rechallenge (following prior progression on TT in the metastatic setting). Five patients underwent retreatment, and 19 received rechallenge. The BRAF/MEKi median free interval for retreatment was 20.9months (range 12.4-57.3), with an ORR of 20%, and median PFS and OS of 5.5 and 8.4months, respectively. The median free interval of TT for rechallenge was 6.8months, with an ORR of 31.6%, and median PFS and OS of 5.7 and 7.6months. Patients with ECOG ≤ 1 experienced longer survival with rechallenge (8.2 vs 4.3months; HR 9.07 [95% CI 1.37-59.8]; p = 0.022). Retreatment or rechallenge with BRAF/MEKi in the metastatic setting has shown clinical activity in patients with metastatic melanoma who lack therapeutic alternatives to prolong survival. Therefore, in our experience, it may represent a valid therapeutic strategy for selected patients. GOV: NCT03605771 (REGISTRATION DATE: 20-07-2018): NCT03605771.

Plaque modification is crucial for successful stent expansion in calcified coronary lesions. Although rotational atherectomy (RA) improves initial procedural success compared to balloon predilatation, data comparing elective versus bailout RA, particularly in chronic kidney disease (CKD) patients, are scarce. To perform a cost analysis of elective RA (E-RA) versus bailout RA (B-RA) to treat severely calcified lesions in patients with CKD, comparing procedural material cost and total healthcare cost. This prospective, multicentre, randomized study compared the costs, safety, and efficacy of E-RA versus B-RA in severely calcified lesions in CKD patients. Participants were randomized 1:1. The primary endpoint was total healthcare cost at 30 days; secondary endpoints included procedural success, stent expansion, and in-hospital complications. One hundred and twenty-four patients were enrolled (62 per group). The mean age was 77.3 ± 8.3 years; 69.4% were male. There were no baseline clinical differences between both treatment arms. Procedural success was similar (B-RA: 95.2% vs. E-RA: 93.6%; p = 0.69), but crossover was higher in B-RA (20.9% vs. 4.8%; p = 0.014). Procedural complications were more frequent in the elective group (6.5% vs. 22.5%; p = 0.04). The B-RA group tended to higher balloon cost (2100.3 vs. 1485.1€; p = 0.06), while E-RA had higher burr costs (374.2 vs. 1408.8€; p < 0.01) and tended toward higher stent costs (2396.7 vs. 2836.1€; p = 0.06). Overall, procedural material costs were higher in E-RA (6676.9 vs. 7683.3€; p = 0.02), but total healthcare costs were not significantly different (12569.1 vs. 14879.1€; p = 0.09). Total healthcare costs were comparable between B-RA and E-RA. A substantial number of patients with CKD and severe CAC required crossover from B-RA, highlighting the potential benefit of E-RA. Besides, the high number of complications underscores the need for expert operators.