BRAF mutational status is associated with survival outcomes in locally advanced resectable and metastatic NSCLC.

BACKGROUND: Immunotherapy-based treatments have demonstrated high efficacy in patients with advanced and locally advanced non-small-cell lung cancer (NSCLC). BRAF mutations affect a small but significant fraction of NSCLC. The efficacy of these therapies in this subgroup of patients is unknown. MATERIALS AND METHODS: Plasma and tissue samples from 116 resectable stage IIIA/B NSCLC patients, included in NADIM and NADIM II clinical trials (NADIM cohort), and from a prospective academic cohort with 84 stage IV NSCLC patients (BLI-O cohort), were analyzed by next-generation sequencing. RESULTS: The p.G464E, p.G466R, p.G466V, p.G469V, p.L597Q, p.T599I, p.V600E (n = 2) BRAF mutations, were identified in four (3.45 %) samples from the NADIM cohort, all of which were cases treated with neoadjuvant chemoimmunotherapy (CH-IO), and four (4.76 %) samples from the BLI-O cohort, corresponding to cases treated with first-line immunotherapy (n = 2) or CH-IO (n = 2). All these patients were alive and had no evidence of disease at data cut-off. Conversely, patients with BRAF wild-type (wt) tumors in the BLI-O cohort had a median progression-free survival (PFS) of 5.49 months and a median overall survival (OS) of 12.00 months (P-LogRank = 0.013 and 0.046, respectively). Likewise, PFS and OS probabilities at 36 months were 60.5 % and 76.1 % for patients with BRAF-wt tumors in the NADIM cohort. The pathological complete response (pCR) rate after neoadjuvant CH-IO in patients with BRAF-positive tumors (n = 4) was 100 %, whereas the pCR rate in the BRAF-wt population was 44.3 % (RR: 2.26; 95 % CI: 1.78-2.85; P < 0.001). CONCLUSION: BRAF mutations may be a good prognostic factor for advanced and locally advanced NSCLC patients undergoing immunotherapy-based treatments.

Assessment of exposure-response relationship for bevacizumab in patients with metastatic colorectal cancer.

Limited literature is available for bevacizumab exposure-response relationship and there is not a concentration threshold associated with an optimal disease control. This prospective observational study in patients with metastatic colorectal cancer (mCRC) aims to evaluate, in a real-life setting, the relationship between bevacizumab through concentrations at steady state (Ctrough, SS) and disease control. Ctrough, SS were drawn, coinciding with the radiological evaluation of the response (progression or clinical benefit). Generalized estimating equations (GEE) analysis was performed. To test the association between Ctrough, SS in each patient with overall survival (OS) or progression-free survival (PFS), Cox proportional hazard models were developed. Data included 50 bevacizumab Ctrough, SS from 27 patients. The GEE model did not suggest any positive association between bevacizumab Ctrough, SS and clinical benefit (OR 0.99, 95% CI: 0.98-1.02, p = 0.863). The Cox regression showed association between higher median Ctrough, SS with better OS (HR 0.86, 95% CI: 0.73-1.01, p = 0.060), but not with PFS. We cannot confirm a relationship between bevacizumab Ctrough, SS and clinical benefit but this is the first real-world study trying to show a relationship between bevacizumab Ctrough, SS and disease control in mCRC. It was conducted in a small sample size which reduces the level of evidence. Further controlled randomized studies with a sufficient number of patients are required.

Assessment of exposure-response relationship for cetuximab in patients with metastatic colorectal cancer and head and neck cancer.

OBJECTIVE: There is limited scientific evidence on the cetuximab exposure-response relationship and no concentration threshold has been associated with optimal disease control. The aims were to assess, in a real-life setting, the  relationship between steady state cetuximab concentrations (Ctrough, SS) and  disease control. METHOD: A prospective observational study in patients with metastatic colorectal cancer or head and neck cancer treated with cetuximab.  Steady state trough concentrations were compared with the results of  radiological assessment of response (progression or clinical benefit).  Generalized estimating equations analysis was performed. To test the  association between steady state concentrations and overall survival and  progression-free survival, Cox proportional hazard models were developed. An  optimal cut-off point was searched using the area under the receiver operating  characteristic curve. RESULTS: A total of 30 steady state cetuximab concentrations from 16 patients  were analysed. Median Ctrough, SS was 26.86 mg/L and there was marked  inter- and intraindividual variability (standard deviation 32.4 mg/L and 16.9 mg/L, respectively). A positive association was found between cetuximab  Ctrough, SS and clinical benefit (odds ratio 1.24, 95% confidence interval:  0.95-1.63, p = 0.113), although without reaching statistical significance. The  area under the receiver operating characteristic curve (n = 30) had moderate  discrimination power (0.71; 95% confidence interval 0.49­0.93), and the  empirical optimal cutoff point was 19.12 mg/L. However, no association was  observed between cetuximab Ctrough, SS and survival in metastatic colorectal  cancer or neck cancer patients. CONCLUSIONS: We cannot confirm a relationship between cetuximab Ctrough,  SS and disease control despite a positive association. This study was  conducted with a small sample, which reduces the power analysis. Further  controlled randomised studies with a sufficient number of patients are needed.

OBJETIVO: Evaluar, en condiciones de vida real, la relación entre las concentraciones valle en estado estacionario de cetuximab y el control de  la enfermedad, así como buscar la relación entre estas concentraciones y la supervivencia. Además, estudiar si existe una concentración límite que se  pueda asociar con la probabilidad de beneficio clínico.Método: Estudio observacional prospectivo llevado a cabo en pacientes con  cáncer colorrectal metastásico o cáncer de cabeza y cuello en tratamiento con  cetuximab. Se realizó un análisis de regresión de ecuaciones de estimación  generalizadas para evaluar la asociación entre la concentración valle en estado  estacionario de cetuximab y la respuesta al tratamiento (progresión o beneficio  clínico). Mediante modelos de riesgos proporcionales de Cox, se  evaluó la asociación entre la mediana de concentraciones valle en estado  estacionario de cetuximab en cada paciente o la última medida con la  supervivencia global y la supervivencia libre de progresión, en cada una de las  patologías. Asimismo, se buscó un punto de corte óptimo a través del área  bajo la curva de características operativas del receptor. RESULTADOS: Se analizaron 30 muestras de 16 pacientes. La concentración valle en estado estacionario mediana fue 26,86 mg/l y se  encontró una gran variabilidad inter e intraindividual (desviación estándar de  32,4 y 16,9 mg/l, respectivamente). Se observó una asociación positiva entre  la concentración valle en estado estacionario y el beneficio clínico (odds ratio  1,24; intervalo de confianza del 95%: 0,95-1,63; p = 0,113), aunque no alcanzó significación estadística debido a la baja potencia. El área bajo la  curva de características operativas del receptor de las concentraciones (n =  30) tuvo una moderada capacidad discriminatoria (área bajo la curva de  características operativas del receptor 0,710; intervalo de confianza del 95%:  0,49-0,93) y el punto de corte estimado fue de 19,12 mg/l. Sin embargo, no  se observó relación entre la supervivencia y las concentraciones valle en  estado estacionario en ninguna de las patologías. CONCLUSIONES: No se ha podido confirmar una relación entre exposición a  cetuximab y eficacia, a pesar de encontrar una tendencia positiva en el control  de la enfermedad con el aumento de la concentración valle en estado  estacionario. El nivel de evidencia se vio reducido por la pequeña muestra de  pacientes en cada grupo, por lo que se necesitan estudios aleatorizados y  controlados, con un número suficiente de pacientes, para evaluar  adecuadamente esta relación.

Degree of technological implementation in intravenous chemotherapy management in hospitals of the Autonomous Community of Madrid.

OBJECTIVE: To understand the degree of technological implementation in the processes of preparation and administration of cytostatics drugs that is available in those hospitals of the Autonomous Community of Madrid where intravenous chemotherapy is prepared. METHOD: A descriptive observational study through the completion of a survey targeted to the staff responsible for the preparation of this type of treatments. RESULTS: The degree of implementation of assisted electronic prescription is high, there is a medium degree in the case of bar code reading technology, and low in terms of vial re-labelling and gravimetric and voice control for preparation. CONCLUSIONS: There is a large room for improvement regarding traceability in the process of preparation and administration of intravenous chemotherapy.

Objetivo: Conocer el grado de implantación tecnológica en los procesos de preparación y administración de citostáticos del que disponen los hospitales de la Comunidad de Madrid en los que se elabora quimioterapia intravenosa.Método: Estudio observacional descriptivo mediante la cumplimentación de una encuesta dirigida al personal responsable de la elaboración de este tipo de tratamientos.Resultados: El grado de implantación de la prescripción electrónica asistida es elevado, medio en el caso de tecnología de lectura de código de barras y bajo en reetiquetado de viales y control gravimétrico y por voz de la elaboración.Conclusiones: Existe un amplio margen de mejora en lo que se refiere a la trazabilidad del proceso de elaboración y administración de mezclas intravenosas de quimioterapia.