Eficácia e Segurança de Regorafenibe em Pacientes com Características de Bom Prognóstico no Tratamento do Câncer Colorretal Metastático: Análise de Subgrupo do Estudo CORRECT

Autores

DOI:

https://doi.org/10.32635/2176-9745.RBC.2022v68n4.2727

Palavras-chave:

inibidores de proteínas quinases, neoplasias colorretais, metástase neoplásica, análise de sobrevida

Resumo

Introdução: O câncer colorretal (CCR) e o segundo mais incidente e, quando metastático, apresenta taxa de sobrevida de 14% em cinco anos. Regorafenibe e um inibidor de tirosina-quinase (ITQ) aprovado para CCR metastático (CCRm) com aumento comprovado de sobrevida global (SG). Objetivo: Explorar resultados de eficácia e segurança de regorafenibe em pacientes com CCRm e características de bom prognostico (CBP). Método: Analise de subgrupo do estudo CORRECT, com participantes divididos de acordo com CBP, seguindo os critérios: Eastern Cooperative Oncology Group (ECOG) 0, tempo de doença metastática maior que 18 meses, até três sítios metastáticos e ausência de metástase hepática. Eficácia comparada com teste de log-rank estratificado e hazad ratios (HR) calculados com o modelo de Cox. Resultados: Dos 760 participantes randomizados, 292 (34,5%) apresentavam CBP; 185 (63,4%) receberam regorafenibe; 107 (35,6%), placebo. Para o grupo CBP, a mediana SG foi 10,9 meses (IC95%:8,8-12,3) para regorafenibe e 7,3 meses (IC95%:5,6-9,1) para placebo, com 39% de redução no risco de morte (HR 0,61; IC95%:0,43-0,88; p=0,0069). A mediana de sobrevida livre de progressão (SLP) foi de 3,5 meses (IC95%:3,0-3,9) versus 1,8 mês (IC95%:1,7-1,8) respectivamente, com 61% de redução no risco de progressão da doença ou morte (HR 0,39; IC95%:0,30-0,52; p<0,0001). Os eventos adversos graus 3 e 4 foram mais frequentes para regorafenibe. Após definição de valor basal para escores de qualidade de vida (EQ-5D), estes descaíram menos para regorafenibe comparados com placebo (0,687 versus 0,592) com diferença significativa de 0,09. Conclusão: Pacientes com CBP que receberam regorafenibe melhoraram SG e SLP com menor deterioração da qualidade de vida comparado com placebo.

Downloads

Não há dados estatísticos.

Referências

Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-49. doi: https://doi.org/10.3322/caac.21660 DOI: https://doi.org/10.3322/caac.21660

Arnold M, Sierra MS, Laversanne M, et al. Global patterns and trends in colorectal cancer incidence and mortality. Gut. 2017;66(4):683-91. doi: https://doi.org/10.1136/gutjnl-2015-310912 DOI: https://doi.org/10.1136/gutjnl-2015-310912

Center MM, Jemal A, Ward E. International trends in colorectal cancer incidence rates. Biomarcadores de Epidemiol de Câncer Anterior.2009;18(6):1688-94. doi: https://doi.org/10.1158/1055-9965.EPI-09-0090 DOI: https://doi.org/10.1158/1055-9965.EPI-09-0090

American Cancer Society [Internet]. Kennesaw (GA): American Cancer Society; c2022. Key statistics for colorectal cancer: How common is colorectal cancer? [revised 2022 Jan 12; cited 2022 May 30]. Available from: https://www.cancer.org/cancer/colon-rectal-cancer/about/key-statistics.html

Cutsem E, Cervantes A, Adam R, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016;27(8):1386-1422. doi: https://doi.org/10.1093/annonc/mdw235 DOI: https://doi.org/10.1093/annonc/mdw235

Messersmith WA. NCCN Guidelines updates: management of metastatic colorectal cancer. J Natl Compr Canc Netw. 2019;17(5.5):599-601. doi: https://doi.org/10.6004/jnccn.2019.5014

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7-34. doi: https://doi.org/10.3322/caac.21551 DOI: https://doi.org/10.3322/caac.21551

Van Cutsem E, Cervantes A, Nordlinger B, et al. Metastatic colorectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2014;25(Suppl 3):iii1-9. doi: https://doi.org/10.1093/annonc/mdu260 DOI: https://doi.org/10.1093/annonc/mdu260

Wilhelm SM, Dumas J, Adnane L, et al. Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. Int J Cancer. 2011;129(1):245-55. doi: https://doi.org/10.1002/ijc.25864 DOI: https://doi.org/10.1002/ijc.25864

Li J, Qin S, Xu R, et al. Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2015;16(6):619-29. doi: https://doi.org/10.1016/S1470-2045(15)70156-7 DOI: https://doi.org/10.1016/S1470-2045(15)70156-7

Grothey A, Van Cutsem E, Sobrero A, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013;381(9863):303-12. doi: https://doi.org/10.1016/S0140-6736(12)61900-X DOI: https://doi.org/10.1016/S0140-6736(12)61900-X

Van Cutsem E, Martinelli E, Cascinu S, et al. Regorafenib for patients with metastatic colorectal cancer who progressed after standard therapy: results of the large, single-arm, open-label phase IIIb CONSIGN study. Oncologist. 2019;24(2):185-92. doi: https://doi.org/10.1634/theoncologist.2018-0072 DOI: https://doi.org/10.1634/theoncologist.2018-0072

Adenis A, de la Fouchardiere C, Paule B, et al. Survival, safety, and prognostic factors for outcome with Regorafenib in patients with metastatic colorectal cancer refractory to standard therapies: results from a multicenter study (REBECCA) nested within a compassionate use program. BMC Cancer. 2016;16:412. doi: https://doi.org/10.1186/s12885-016-2440-9 DOI: https://doi.org/10.1186/s12885-016-2440-9

Associação Médica Mundial. Declaração de Helsinque da Associação Médica Mundial (WMA): princípios éticos para pesquisa médica envolvendo seres humanos [Internet]. Jorge MR, tradudor. In: 64ª Assembleia Geral da WMA; 2013 out; Fortaleza. França: World Medical Association; 2013 [acesso 2022 maio 5]. Disponível em: https://arquivos.amb.org.br/_downloads/289493001383134046_DECLARACAODEHELSINQUE.pdf

Conselho Internacional para Harmonização de Requisitos Técnicos para Produtos Farmacêuticos de Uso humano. Guia Harmonizado do ICH: adendo integrado ao ICH E6(R1): guia de boas práticas clínicas E6(R2) [Internet]. Versão vigente do passo 4 de 9. Brasília (DF): Anvisa; 2016 nov [acesso 2022 maio 30]. Disponível em: http://antigo.anvisa.gov.br/documents/33836/2492465/Guia+de+Boas+Pr%C3%A1ticas+Cl%C3%ADnicas+ICH+E6%28R2%29+-+Traduzido+para+portugu%C3%AAs%2C+vers%C3%A3o+Anvisa+de+Novembro-2019/93e4d18c-7e86-4e71-9283-7740e42d7ff6

Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228-47. doi: https://doi.org/10.1016/j.ejca.2008.10.026 DOI: https://doi.org/10.1016/j.ejca.2008.10.026

National Cancer Institute, Cancer Therapy Evaluation Program. Common Terminology Criteria for Adverse Events v3.0 (CTCAE) [Internet]. Bethesda (MD): CETEP; 2006 Aug 9 [cited 2022 Oct 19]. Available from: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm

European Organisation for Research and Treatment of Cancer Quality of Life. EORTC QLQ-C30 [Internet]. Version 3 [place unknown]: EORTC Quality of Life Group; c1995 [cited 2022 May 30]. Available from: https://www.eortc.org/app/uploads/sites/2/2018/08/Specimen-QLQ-C30-English.pdf

Health Questionnaire (EQ-5D-5L) [Internet]. United Kingdom: EuroQol; c2009 [cited 2022 May 30]. Available from: https://aci.health.nsw.gov.au/__data/assets/pdf_file/0003/632847/EuroQol-5-Dimension.pdf

Visual Analogue Scale (VAS): 3 02 a pain scales [Internet]. Adapted from: Warden V, Hurley AC, Volicer L. Development and psychometric evaluation of the pain assessment in advanced dementia (PAINAD) scale. J Am Med Dir Assoc. 2003;4:9-15 [revised 2011; cited 2022 May 5]. Available from: https://eportfolios.macaulay.cuny.edu/reisf16/files/2016/09/pain-scale-visual.pdf

Pickard AS, Neary MP, Cella D. Estimation of minimally important differences in EQ-5D utility and VAS scores in cancer. Health Qual Life Outcomes. 2007;5:70. doi: https://doi.org/10.1186/1477-7525-5-70 DOI: https://doi.org/10.1186/1477-7525-5-70

Aljubran A, Elshenawy MA, Kandil M, et al. Efficacy of regorafenib in metastatic colorectal cancer: a multi-institutional retrospective study. Clin Med Insights Oncol. 2019;13:1179554918825447. doi: https://doi.org/10.1177/1179554918825447 DOI: https://doi.org/10.1177/1179554918825447

Novakova-Jiresova A, Kopeckova K, Boublikova L, et al. Regorafenib for metastatic colorectal cancer: an analysis of a registry-based cohort of 555 patients. Cancer Manag Res. 2020;12:5365-72. doi: https://doi.org/10.2147/CMAR.S255332 DOI: https://doi.org/10.2147/CMAR.S255332

Yamaguchi K, Komatsu Y, Satoh T, et al. Large-scale, prospective observational study of regorafenib in japanese patients with metastatic colorectal cancer in a real-world clinical setting. Oncologist. 2019;24(7):e450-e457. doi: https://doi.org/10.1634/theoncologist.2018-0377 DOI: https://doi.org/10.1634/theoncologist.2018-0377

Bekaii-Saab TS, Ou FS, Ahn DH, et al. Regorafenib dose-optimisation in patients with refractory metastatic colorectal cancer (ReDOS): a randomised, multicentre, open-label, phase 2 study. Lancet Oncol. 2019;20(8):1070-82. doi: https://doi.org/10.1016/S1470-2045(19)30272-4 DOI: https://doi.org/10.1016/S1470-2045(19)30272-4

Cancer G. Real-world adherence in patients with metastatic colorectal cancer treated with trifluridine plus tipiracil or regorafenib. Oncologist. 2020;25(1):e75-e84. doi: https://doi.org/10.1634/theoncologist.2019-0240 DOI: https://doi.org/10.1634/theoncologist.2019-0240

Kidd MT, Wilcox RE, Rogers J, et al. Efficacy of chemotherapy after treatment with regorafenib in metastatic colorectal cancer (mCRC). J Clin Oncol. 2015;33(Suppl 3):678-8. doi: https://doi.org/10.1200/jco.2015.33.3_suppl.678 DOI: https://doi.org/10.1200/jco.2015.33.3_suppl.678

Loupakis F, Antonuzzo L, Bachet JB, et al. Practical considerations in the use of regorafenib in metastatic colorectal cancer. Ther Adv Med Oncol. 2020;12:1758835920956862. doi: https://doi.org/10.1177/1758835920956862 DOI: https://doi.org/10.1177/1758835920956862

Downloads

Publicado

2022-10-24

Como Citar

1.
Palhares RR, Britto G do C, Su Y, Le Berre M-A, Henriques RS, Navachi FV, Pereira DCF, Ostojic H, Azevedo GA, Van Cutsem E. Eficácia e Segurança de Regorafenibe em Pacientes com Características de Bom Prognóstico no Tratamento do Câncer Colorretal Metastático: Análise de Subgrupo do Estudo CORRECT. Rev. Bras. Cancerol. [Internet]. 24º de outubro de 2022 [citado 28º de novembro de 2022];68(4):e-162727. Disponível em: https://rbc.inca.gov.br/index.php/revista/article/view/2727

Edição

Seção

ARTIGO ORIGINAL