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DOI: 10.26790/BJO20171346A177
Uso de regorafenibe em pacientes com câncer colorretal metastático previamente tratados com bevacizumabe ou aflibercepte: experiência clínica uni-institucional
Use of regorafenibe in patients with metastastic colorretal cancer previously treated with bevacizumab or aflibercept: uni-institutional clinical experience
RESUMO
Introdução: A adição de terapias alvo antiangiogênicas, como o bevacizumabe e aflibercepte, promoveu ganho em sobrevida global (SG) para pacientes com câncer colorretal metastático (CCRm) em segunda linha, quando combinado a quimioterapia padrão. Mais recentemente, o estudo CORRECT demonstrou que regorafenibe, uma droga oral e inibidora de várias tirosino-quinases,, proporcionou ganho em SG em pacientes com CCRm refratário. Porém, a eficácia e a tolerabilidade de regorafenibe no nosso meio não foi reportada, bem como os desfechos pós uso de aflibercepte.
Objetivo: Avaliar os desfechos clínicos globais de pacientes brasileiros tratados com regorafenibe e também os desfechos de acordo com o tipo de antiangiogênico prévio, (A) aflibercepte ou (B) bevacizumabe. Métodos: Estudo retrospectivo unicêntrico de pacientes com CCRm tratados com regorafenibe em programa de acesso expandido.
Resultados: Foram incluídos 24 pacientes: 14 receberam bevacizumabe (Grupo B) e 10, aflibercepte (Grupo A). A maioria dos pacientes apresentava adenocarcinoma de cólon e todos com ECOG 0 ou 1. A proporção de pacientes com tumores RAS selvagem foi 30% no Grupo A e 42,8% no Grupo B. A melhor resposta foi doença estável por RECIST 1.1. A sobrevida global mediana foi 8,15 meses no Grupo A, 5,8 meses no Grupo B e de 6,16 meses na análise global. A presença de escavação de metástases pulmonares (45% no Grupo B e 66%% no Grupo A) não influenciou a sobrevida global. Cerca de 80% dos pacientes do Grupo A recebeu terapia a ntitumoral após progressão ao regorafenibe versus 35,7% no Grupo B. Fadiga, reação mão-pé-pele, elevação de enzimas hepáticas e hipertensão arterial foram os eventos adversos mais comuns relacionados a regorafenibe, sendo que no Grupo A, as toxicidades graus 2 ou 3 ocorreram em 90% em dos casos, e no Grupo B, ocorreram em 78,50%. Não houve toxicidades graus 4 ou 5.
Conclusão: Nesta série retros pectiva, a sobrevida mediana do grupo bevacizumabe foi semelhante aos estudos clínicos. No grupo aflibercepte, a sobrevida mediana foi numericamente maior. Porém, este achado pode ser atribuído a viés de seleção. O perfil de toxicidade foi semelhante ao da literatura, exceto por menos diarréia, um efeito adverso comum no estudo CORRECT, com população norte-americana.
ABSTRACT
Background: The addition of antiangiogenic therapies, such as bevacizumab and aflibercept, resulted in overall survival (OS) gain for patients with metastatic colorectal (mCRC). Recently the CORRECT trial demonstrated that regorafenib, an oral multi-kinase inhibitor, also led to improved OS in patients with refractory mCRC. However, the efficacy and safety of regorafenib has not been described in our region, as neither the outcomes following treatment with aflibercept. Objective: To evaluate the overall treatment outcomes of Brazilian patients treated with regorafenib as well as according to type of prior antiangiogenic agent, aflibercept (Group A) or bevacizumab (Group B).
Methods: Retrospective unicenter study of mCRC patients treated with regorafenibe within an Expanded Access Program.
Results: We included 24 patients: 14 received B and 10, received A. Most patients had colon cancer and all had ECOG 0 or 1. Wild type RAS mCRC was present in 30% of Group A and in 42.8% of Group B. The best response by RECIST 1.1 was stable disease. Median OS times were 8.15 months in Group A, 5.8 months in Group B and 6.16 months for the whole group. Cavitation of pulmonary metastases (45% in Group B and 66%% in Group A) did not influence OS. Nearly 80% of Group A patients received post-progression treatments versus 35.7% in Group B. Fatigue, hand-foot skin reactions, elevated liver enzymes and arterial hypertension were the most common adverse events related to regorafenib, with grade 2/3 occurring in 90% of Group A and in 78.50% of Group B. There were no grade 4 toxicities.
Conclusion: In this retrospective series, the median OS of patients treated with regorafenib after bevacizumab was similar to that reported by phase III trials. For those previously treated with aflibercept, the median OS was numerically longer in comparison with the bevacizumab group, although this could be explained by selection bias. The toxicity profile of regorafenibe was also similar to that described in the literature except for less diarrhea, which was rare among Brazilian patients.
Publication History
Received: 20 December 2017
Accepted: 30 December 2017
Article published online:
25 February 2025
© 2017. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/)
Thieme Revinter Publicações Ltda.
Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil
Rodrigo Nogueira Fogace, Luiz Antonio Senna Leite, Daniela Ribeiro Nebuloni, Giovanni Mendonça Bariani, Fernanda Capareli, Lucila Soares da Silva Rocha, Paulo Marcelo Gehm Hoff, Thomas Giollo Rivelli, Rachel P. Riechelmann. Uso de regorafenibe em pacientes com câncer colorretal metastático previamente tratados com bevacizumabe ou aflibercepte: experiência clínica uni-institucional. Brazilian Journal of Oncology 2017; 13: e-BJO20171346A177.
DOI: 10.26790/BJO20171346A177
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