Everolimus plus endocrine therapy beyond CDK4/6 inhibitors progression for HR+ /HER2- advanced breast cancer: a real-world evidence cohort.

PURPOSE: Everolimus in combination with endocrine therapy (ET) was formerly approved as 2nd-line therapy in HR(+)/HER2(-) advanced breast cancer (aBC) patients (pts) progressing during or after a non-steroidal aromatase inhibitor (NSAI). Since this approval, the treatment landscape of aBC has changed dramatically, particularly with the arrival of CDK 4-6 inhibitors. Endocrine monotherapy after progression to CDK4/6 inhibitors has shown a limited progression-free survival (PFS), below 3 months. Evidence of the efficacy of everolimus plus ET after CDK4/6 inhibitors is scarce. METHODS: A retrospective observational study of patients with aBC treated with everolimus and ET beyond CDK4/6-i progression compiled from February 2015 to December 2022 in 4 Spanish hospitals was performed. Clinical and demographic data were collected from medical records. The main objective was to estimate the median progression-free survival (mPFS). Everolimus adverse events (AE) were registered. Quantitative variables were summarized with medians; qualitative variables with proportions and the Kaplan-Meier method were used for survival estimates. RESULTS: One hundred sixty-one patients received everolimus plus ET (exemestane: 96, fulvestrant: 54, tamoxifen: 10, unknown: 1) after progressing on a CDK4/6 inhibitor. The median follow-up time was 15 months (interquartile range: 1-56 months). The median age at diagnosis was 49 years (range: 35-90 years). The estimated mPFS was 6.0 months (95%CI 5.3-7.8 months). PFS was longer in patients with previous CDK4/6 inhibitor therapy lasting for > 18 months (8.7 months, 95%CI 6.6-11.3 months), in patients w/o visceral metastases (8.0 months, 95%CI 5.8-10.5 months), and chemotherapy-naïve in the metastatic setting (7.2 months, 95%CI 5.9-8.4 months). CONCLUSION: This retrospective analysis cohort of everolimus plus ET in mBC patients previously treated with a CDK4/6 inhibitor suggests a longer estimated mPFS when compared with the mPFS with ET monotherapy obtained from current randomized clinical data. Everolimus plus ET may be considered as a valid control arm in novel clinical trial designs.

Phase II study of preoperative bevacizumab, capecitabine and radiotherapy for resectable locally-advanced rectal cancer.

BACKGROUND: To evaluate whether the addition of bevacizumab (BVZ) to capecitabine-based chemoradiotherapy in the preoperative treatment of locally advanced rectal cancer (LARC) improves efficacy measured by the pathological complete response (pCR) rate. METHODS: A phase II two-step design was performed. Patients received four cycles of therapy consisting of: BVZ 10 mg/kg in first infusion on day 1 and 5 mg/kg on days 15, 29, 43, capecitabine 1800 mg/m(2)/day 5 days per week during radiotherapy, which consisted of external-beam irradiation (45 Gy in 1.8 Gy dose per session over 5 sessions/week for 5 weeks). Six to eight weeks after completion of all therapies surgery was undergone. To profile the biological behaviour during BVZ treatment we measured molecular biomarkers before treatment, during BVZ monotherapy, and during and after combination therapy. Microvessel density (MVD) was measured after surgery. RESULTS: Forty-three patients were assessed and 41 were included in the study. Three patients achieved a pathological complete response (3/40: 7.5%) and 27 (67.5%) had a pathological partial response, (overall pathological response rate of 75%). A further 8 patients (20%) had stable disease, giving a disease control rate of 95%. Downstaging occurred in 31 (31/40: 77.5%) of the patients evaluated. This treatment resulted in an actuarial 4-year disease-free and overall survival of 85.4 and 92.7% respectively. BVZ with chemoradiotherapy showed acceptable toxicity. No correlations were observed between biomarker results and efficacy variables. CONCLUSION: BVZ with capecitabine and radiotherapy seem safe and active and produce promising survival results in LARC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00847119 . Trial registration date: February 18, 2009.

Analysis of the association of HER-2 low carcinomas and PAM50 assay in hormone receptor positive early-stage breast cancer.

BACKGROUND: HER2-low has emerged as a new predictive biomarker in metastatic breast cancer. However, its prognostic value in early-stage carcinomas needs to be revisited. We aimed to evaluate the association of HER2-low carcinomas with PAM50 risk groups combined with clinicopathological variables in early breast cancer. METHODS: We conducted a retrospective analysis of 332 patients with early-stage breast cancer that underwent PAM50 signature analysis between 2015 and 2021at Hospital Universitario 12 de Octubre (Madrid, Spain). Clinical and pathological variables were collected from medical records. After adjusting for potential confounders, we estimated Odds Ratio (OR) and 95% confidence interval for high-risk PAM50 subgroup, comparing HER2-low versus HER2-zero carcinomas by multivariable logistic regression. P values below 0.05 were deemed statistically significant. RESULTS: 192 (57%) patients were classified as HER2-low carcinomas. Median follow-up was 34 months. Adjusted OR for high-risk PAM50 when comparing HER2-low versus HER2-zero carcinomas was 1.31 (95% CI: 0.75-2.30, p = 0.33). The multivariable model detected significant associations for Ki-67% (≥20% vs. <20%: OR = 4.03, 95% CI: 2.15-7.56, p < 0.001), T staging category (T2/T3 vs. T1: OR = 3.44, 95% CI: 1.96-6.04, p < 0.001), progesterone receptor (PR ≥ 20% vs. <20%: OR = 0.44, 95% CI: 0.23-0.83, p = 0.01), nodal staging category (N+ vs. N0: OR = 3.8, 95% CI: 1.89-7.62, p < 0.001) and histological grade (grade 2 vs. 1: OR = 2.41, 95% CI: 1.01-5.73, p = 0.04; grade 3 vs 1: OR = 5.40, 95%CI: 1.98-14.60, p = 0.001). CONCLUSIONS: In this early-stage breast cancer cohort, HER2-low was not associated with a high-risk PAM50 compared to HER2-zero carcinomas. Ki-67 ≥ 20%, T2/T3, histological grade 2/3, N+ and PR<20% were significantly associated to a high-risk PAM50.

Análisis de los recursos disponibles para el manejo de la vía aérea en sala de operaciones

RESUMEN Objetivo: determinar los recursos disponibles en las salas de operaciones de nuestro país para manejo de la vía aérea, y qué niveles se alcanzan del algoritmo de vía aérea dificultosa de la Sociedad Americana de Anestesiología (ASA). Se realizó un estudio de corte transversal, documentando en cada sala de operaciones de Montevideo si tenían una bandeja/valija/carro de intubación dificultosa, y todos los dispositivos para intubación, ventilación, supraglóticos, y para abordaje quirúrgico de la vía aérea. Según los niveles alcanzados en el algoritmo de la ASA, los centros quirúrgicos se clasificaron de 1 a 4. Resultados: solo 9/24 centros de adultos alcanzaron los cuatro escalones del algoritmo de la ASA (material para intubación + ventilación + supraglóticos de intubación o fibrobroncoscopio [FBC] + quirúrgico) y 1/19 en niños. seis centros de adultos y cinco pediátricos completaron el tercer escalón (dispositivos intubación + ventilación + supraglóticos de intubación o FBC, ó material quirúrgico). ocho salas de adultos y 11 de niños completaron el segundo escalón (material intubación + ventilación), y una de niños solo llegó al primer escalón. En todos los casos se puede convocar a fibroscopista para la intubación. El conductor estándar y la máscara laríngea están disponibles en todos los centros de adultos. Conclusiones: la mayor parte de los centros quirúrgicos están preparados para manejar adecuadamente la vía aérea prevista mediante la intubación fibróptica, pero en la mayoría los recursos son insuficientes para el abordaje integral de la vía aérea dificultosa o imposible imprevista, según las pautas de la ASA.

SUMMARY Objective: to determine the resources available for airway management in the operating rooms of our country, and the levels reached of the difficult airway algorithm of the American Society of Anesthesiologists (ASA). A transversal cut study was carried out, where it was documented the availability of a difficult intubation tray/bag/cart/ in each operating room of Montevideo, as well as of all necessary intubation, ventilation and supraglottic devices and those required for surgical airway approach. According to the levels of the ASA algorithm reached, surgical centers were classified from 1 to 4. Results: only 9/24 adult centers reached the 4 steps of ASA algorithm (material for intubation + ventilation + airway supraglottic devices or Fiberbronchoscope (FB) + surgical material) and 1/19 in pediatric centers; 6 adult and 5 pediatric centers completed step 3 (intubation + ventilation + airway supraglottic devices or FB, or surgical material); 8 adult rooms and 11 children rooms reached step 2 (intubation + ventilation material), and one pediatric room reached only the first step. In all cases, a fibroscopist may be called for intubation. The standard tube and laryngeal mask are available in all adult centers. Conclusions: most surgical centers are prepared to adequately manage an expected difficult airway through fiberoptic intubation, but, in most cases, resources are insufficient for an integral approach of unexpected difficult or impossible airway, according to ASA guidelines.

RESUMO Objetivo: determinar os recursos disponíveis nas salas de cirurgia de nosso pais para o manejo da via aérea, e que níveis se atingem do algoritmo da via aérea dificil da Sociedade Americana de Anestesiologia (ASA). Realizou-se um estudo de corte transversal, documentando em cada sala de cirurgia de Montevidéu se havia uma bandeja/maleta/carro para intubação dificil, e todos os dispositivos para intubação, ventilação, supragloticos, e para abordagem cirúrgica da via aérea. De acordo com os níveis atingidos no algoritmo da ASA , os centros cirúrgicos foram classificados de 1 a 4. Resultados: somente 9/24 centros de adultos atingiram os 4 degraus do algoritmo da ASA (material para intubação + ventilação + supragloticos de intubação ou fibrobroncoscopio (FBC) + cirúrgico) e 1/19 pediatricos. 6 centros de adultos e 5 pediátricos completaram o terceiro degrau ( dispositivo de intubação + ventilação + supraglotico de intubação e FBC, ou material cirúrgico). 8 salas de adultos e 11 de crianças completaram o segundo degrau (material intubação + ventilação), e uma de criança somente chegou ao primeiro degrau. Em todos os casos se pode convocar fibroscopista para a intubação. O condutor comum e a máscara laríngea estão disponíveis em todos os centros de adultos. Conclusões. A maioria dos centros cirúrgicos estão preparados para lidar adequadamente com a via aérea prevista mediante a intubação fibroptica, mas na maioria deles os recursos são insuficientes para a abordagem integral da via aérea difícil ou impossível imprevista para seguir o protocolo da ASA.