Efficacy and safety of trifluridine/tipiracil (TAS-102) in patients with metastatic colorectal cancer: a systematic review and meta-analysis

Objectives The purpose of this meta-analysis is to evaluate the efficacy and safety of TAS-102 in treating metastatic colorectal cancer (mCRC) using the most recent data available. Methods The literature on the efficacy and safety of TAS-102 versus placebo and/or best supportive care (BSC) in mCRC was obtained through a systematic search of PubMed, Embase, and Web of Science databases through January 2023. Identify the included literature and extract pertinent data, such as the overall survival (OS), progression-free survival (PFS), time to treatment failure (TTF), disease control rate (DCR), incidence of adverse events (AEs) and serious adverse events (SAEs). Results There were eight eligible articles that included 2903 patients (1964 TAS-102 versus 939 Placebo and/or BSC). In this meta-analysis, TAS-102 treatment resulted in longer OS, PFS, TTF, and higher DCR in patients with mCRC versus placebo and/or BSC. TAS-102 improved OS and PFS in subgroup analyses of mCRC patients with KRAS wild-type and KRAS mutant-type. In addition, TAS-102 did not increase the incidence of serious adverse events. Conclusion TAS-102 can enhance the prognosis of mCRC patients whose standard therapy has failed, regardless of KRAS mutation status, and its safety is acceptable (AU)

Efectividad y seguridad de regorafenib y trifluridina/tipiracilo en cáncer colorrectal metastático / Effectiveness and safety of regorafenib versus trifluridine/tipiracil in metastatic colorectal cancer

OBJETIVOS: Comparar la efectividad y seguridad de regorafenib y trifluridina/tipiracilo en pacientes con cáncer de colon metastático en la práctica clínica real. MÉTODOS: Estudio retrospectivo observacional entre febrero 2013 y mayo 2017. Se incluyeron todos los pacientes con cáncer de colon metastático que empezaron tratamiento con regorafenib o trifluridina/tipiracilo. Se recogieron variables demográficas, diagnósticas y terapéuticas; y los efectos adversos y reducciones de dosis para evaluar la seguridad. La supervivencia global (SG) y supervivencia libre de progresión (SLP) se calcularon con el método de Kaplan-Meier, evaluándose las diferencias mediante la determinación del hazard ratio (HR) con un modelo de riesgo proporcional de Cox. RESULTADOS: Se incluyeron 39 pacientes (61,54% mujeres, edad media: 62,69 ± 11,51 años, 76,92% ECOG1, mediana de líneas de tratamiento previas 3,28 ± 1,02; 58,97% RAS mutado, 61,54% presentaban metástasis en el diagnóstico): 10 iniciaron regorafenib y 29 trifluridina/tipiracilo. La mediana de SLP fue 1,77 meses con regorafenib y 2,46 con trifluridina/tipiracilo (HR 1,35 (0,64-2,85), p = 0,428), y de SG 7,00 meses con ambos (HR 1,45 (0,68-3,09), p = 0,335). Las diferencias no fueron estadísticamente significativas. La media de efectos adversos por paciente fue 3,70 ± 2,35 con regorafenib y 2,55 ± 2,16 con trifluridina/tipiracilo, siendo los más frecuentes con regorafenib astenia, diarrea, síndrome mano-pie, hiporexia y mucositis; y con trifluridina/tipiracilo astenia, neutropenia y náuseas. El 30,00% de pacientes con regorafenib y el 27,58% con trifluridina/tipiracilo necesitaron reducir la dosis por toxicidad. CONCLUSIÓN: En nuestro estudio, regorafenib y trifluridina/tipiracilo tienen una efectividad similar y modesta. Los distintos perfiles de toxicidad de los fármacos deben tenerse en cuenta en la selección del tratamiento

PURPOSE: To compare effectiveness and safety of regorafenib and trifluridine/tipiracil in patients with metastatic colorectal cancer in real clinical practice. METHODS: A retrospective observational study including all patients with metastatic colorectal cancer who started treatment with regorafenib or trifluridine/ tipiracil (February 2013-May 2017) was carried out. Demographic, diagnostic and therapeutic variables were collected. Adverse effects and dose reductions were recorded to measure safety. Median progression free survival (PFS) and overall survival (OS) were recorded. Differences in survival were evaluated using the Cox's proportional hazard models to determine the hazard ratio. RESULTS: Throughout the period of the study 39 patients were included (61.54% women, median age 62.69 ± 11.51 years, 76.92% ECOG1, median previous lines 3.28 ± 1.02, 58.97% mutant RAS, 61.54% had metastasis in the diagnosis): 10 patients started treatment with regorafenib and 29 with trifluridine/tipiracil. The median PFS with regorafenib was 1.77 months and with trifluridine/tipiracil 2.46 months (HR 1.35 (0.64-2.85), p = 0.428), and the median OS was 7.00 months with both drugs (HR 1.45 (0.68-3.09), p = 0.335). Differences in survival were not statistically significant

Uso de antineoplásicos orales en situaciones especiales en un hospital de tercer nivel: resultados en la vida real / Use of oral antineoplastic in special situations in a third level hospital: real life results

Objetivo: Analizar la efectividad y seguridad de los antineoplásicos orales (ANEO) autorizados en situaciones especiales en un hospital de tercer nivel y comparar los resultados obtenidos con los de la evidencia disponible empleada para autorizar el uso de estos fármacos. Método: Estudio descriptivo observacional y retrospectivo. Se incluyeron todos los pacientes adultos que iniciaron tratamiento con ANEO en situaciones especiales durante el año 2016. Se recogieron variables demográficas, relacionadas con el tratamiento, y clínicas (supervivencia global (SG), supervivencia libre de progresión (SLP)). Se recogieron reacciones adversas e interacciones detectadas. Se realizó una comparación no ajustada entre los resultados de la evidencia disponible y los de los pacientes del estudio. Resultados: Treinta y cuatro pacientes recibieron tratamiento, el 50% eran hombres, la mediana de edad fue de 58 años (38-80), y presentaron ECOG 1 el 64,7%. La mayoría de los pacientes tratados presentaban diagnóstico de cáncer colorrectal avanzado, tratados con trifluridina-tipiracil, seguidos de palbociclib en cáncer de mama, obteniendo resultados similares a los de la evidencia. La mediana de SLP fue de 2,8 meses (IC 95% 0,8-4,8) y la SG de 8 meses (IC 95% 3,4-12,5) para todos los pacientes. El 26% de los pacientes requirieron una reducción de la dosis debido a la toxicidad del tratamiento. Se encontraron 13 interacciones, que afectaron a 15 pacientes; solo dos de categoría X. Conclusiones: La efectividad de los ANEO en situaciones especiales en nuestro centro es similar al de la evidencia disponible. El impacto en la supervivencia es bajo y los efectos adversos son comunes (AU)

Objective: To analyse the effectiveness and safety of oral antineoplastic drugs (ANEOs) that are authorized in special situations in a third-level hospital and to compare the results obtained with the clinical evidence used for this authorization. Method: Descriptive observational and retrospective study. We included all adult patients who started treatment with ANEO in special situations during the year 2016. We collected demographic, treatment-related and clinical variables (overall survival (OS), progression-free survival (PFS)). Adverse reactions and detected interactions were collected. An unadjusted comparison was made between the results of the available evidence and those of the study patients. Results: 34 patients were treated, 50% were men, the median age was 58 years (38-80) and they presented ECOG 1 in 64.7%. Most of the treated patients were diagnosed with advanced colorectal cancer, treated with trifluridine-tipiracil, followed by palbociclib in breast cancer, obtaining results similar to those of the evidence. The median PFS was 2.8 months (95% CI 0.8-4.8) and the 8-month SG (95% CI 3.4-12.5) for all patients. 26% of patients required dose reduction because of treatment toxicity. We found 13 interactions, which affected 15 patients, only two of category X. Conclusions: The effectiveness of ANEO in special situations in our center is similar to that of available evidence. The impact on survival is low and adverse effects are common (AU)

Efficacy of trifluridine and tipiracil (TAS-102) versus placebo, with supportive care, in a randomized, controlled trial of patients with metastatic colorectal cancer from Spain: results of a subgroup analysis of the phase 3 RECOURSE trial

Purpose. TAS-102 is a combination of the thymidine-based nucleoside analog trifluridine and the thymidine phosphorylase inhibitor tipiracil. Efficacy and safety of TAS-102 in patients with metastatic colorectal cancer (mCRC) refractory or intolerant to standard therapies were evaluated in the phase 3 RECOURSE trial. Results of RECOURSE demonstrated significant improvement in overall survival (OS) and progression-free survival (PFS) with TAS-102 versus placebo [hazard ratio (HR) = 0.68 and 0.48 for OS and PFS, respectively; both P < 0.001]. The current analysis evaluates efficacy and safety of TAS-102 in the RECOURSE Spanish subgroup. Methods. Primary and key secondary endpoints were evaluated in a post hoc analysis of the RECOURSE Spanish subgroup, using univariate and multivariate analyses. Safety and tolerability were reported with descriptive statistics. Results. The RECOURSE Spanish subgroup included 112 patients (mean age 61 years, 62 % male). Median OS was 6.8 months in the TAS-102 group (n = 80) versus 4.6 months in the placebo group (n = 32) [HR = 0.47; 95 % confidence interval (CI): 0.28-0.78; P = 0.0032). Median PFS was 2.0 months in the TAS-102 group and 1.7 months in the placebo group (HR = 0.47; 95 % CI: 0.30-0.74; P = 0.001). Eighty (100 %) TAS-102 versus 31 (96.9 %) placebo patients had adverse events (AEs). The most common drug-related ≥Grade 3 AE was neutropenia (40 % TAS-102 versus 0 % placebo). There was 1 (1.3 %) case of febrile neutropenia in the TAS-102 group versus none in the placebo group. Conclusions. In the RECOURSE Spanish subgroup, TAS-102 was associated with significantly improved OS and PFS versus placebo, consistent with the overall RECOURSE population. No new safety signals were identified (AU)

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Terapéutica antivírica en pediatría: situación actual y perspectivas de futuro / Antiviral therapy in pediatrics: present situation and future perspectives

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