Brazilian cohort results of the PRECONNECT study: safety and efficacy of trifluridine/tipiracil in metastatic colorectal cancer

ABSTRACT

PRECONNECT is a multicenter study demonstrating the efficacy and tolerability of trifluridine/tipiracil in adult patients with histologically confirmed adenocarcinoma of the colon or rectum and pretreated metastatic lesions. The current article describes the characteristics and outcomes of the Brazilian cohort of patients who underwent trifluridine/tipiracil therapy within PRECONNECT. Brazilian patients (n=55) received oral trifluridine/tipiracil 35mg/m² twice daily on days 1-5 and 8-12 of each 28-day cycle. The primary endpoint was safety including time to ECOG (Eastern Cooperative Oncology Group) PS (performance status) deterioration, and the secondary endpoints included progression-free survival (PFS) and quality of life (QoL). Baseline characteristics showed only 34.5% of patients underwent ≥3 lines of treatment, 29.1% presented ≥3 metastatic sites and 52.7% showed an ECOG PS of 0. The disease control rate (DCR) was 32.0% and 28.6% in patients with one and two metastatic sites, respectively, the median PFS was 3.0 months (95%CI: 2.5-3.4), and the time to ECOG PS deterioration (≥2) was 5.4 months. Drug-related treatment-emergent adverse events (TEAE) were observed at least once in 87.3% of patients, and the most common (≥40% of patients) hematological TEAEs were neutropenia and anemia; there was no febrile neutropenia case. The shorter time to ECOG PS deterioration showed in the Brazilian subset of patients is likely due to late diagnosis setting compared to the global population, despite that trifluridine/tipiracil showed good DCR results, including patients with two metastatic sites. In conclusion, safety and efficacy results provide confidence in routine practice use and are in line with the PRECONNECT study

RESUMO

O PRECONNECT é um estudo multicêntrico que demonstra a eficácia e tolerabilidade de trifluridina/tipiracil em pacientes adultos com adenocarcinoma de cólon ou reto confirmado histologicamente e lesões metastáticas pré-tratadas. O presente artigo descreve as características e os resultados da coorte brasileira de pacientes submetidos à terapia com trifluridina/tipiracil dentro do PRECONNECT. Pacientes brasileiros (n=55) receberam trifluridina/tipiracil oral 35mg/m² duas vezes ao dia, nos dias 1 -5 e 8-12 de cada ciclo de 28 dias. O desfecho primário foi a segurança, incluindo o tempo até a deterioração do ECOG (Eastern Cooperative Oncology Group) SD (status de desempenho), e os desfechos secundários incluíram sobrevida livre de progressão (SLP) e qualidade de vida (QV). As características basais mostraram que apenas 34,5% dos pacientes foram submetidos a ≥3 linhas de tratamento, 29,1% apresentaram ≥3 sítios metastáticos e 52,7% apresentaram ECOG SD de 0. A taxa de controle da doença (TCD) foi de 32,0% e 28,6% em pacientes com um e dois sítios metastáticos, respectivamente, a PFS mediana foi de 3,0 meses (IC95%: 2,5-3,4) e o tempo para deterioração do ECOG SD (≥2) foi de 5,4 meses. Os eventos adversos emergentes do tratamento (EAET) relacionados ao medicamento foram observados pelo menos uma vez em 87,3% dos pacientes, e os EAETs hematológicos mais comuns (≥40% dos pacientes) foram neutropenia e anemia; não houve caso de neutropenia febril. O menor tempo para deterioração do ECOG SD mostrado no subgrupo brasileiro de pacientes é provavelmente devido ao diagnóstico tardio em comparação com a população global, apesar de que trifluridina/tipiracil mostrou bons resultados de TCD, incluindo pacientes com dois sítios metastáticos. Em conclusão, os resultados de segurança e eficácia fornecem confiança no uso da prática de rotina e estão de acordo com o estudo PRECONNECT.

Keywords:

Trifluridine/tipiracil - Colorectal cancer - Metastatic colorectal cancer - Refractory disease

Descritores:

Trifluridina/tipiracil - Câncer colorretal - Câncer colorretal metastático - Doença refratária

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