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AtualizadoTer, 03 Ago 2021 4pm

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Daichii Sankyo

ESMO lança escala para apoiar medicina de precisão

AURO DEL GIGLIO NET OKA ESMO lançou uma proposta de classificação para facilitar e harmonizar a medicina de precisão no tratamento do câncer. Através da ESMO Scale of Clinical Actionability Target (ESCAT), a sociedade europeia apresenta uma escala com seis níveis de evidências para apoiar o uso de alvos moleculares acionáveis na prática clínica. A classificação está em artigo de Mateo et al, no Annals of Oncology. O oncologista Auro Del Giglio (foto), coordenador do Serviço de Oncologia Clínica do IBCC e do HCOR, comenta a classificação.

A ESCAT considera diferentes níveis de evidências e implicações para o manejo do paciente. No nível IA da escala estão os alvos terapêuticos prontos para serem incluídos nas decisões clínicas de rotina, com base em estudos que demonstraram ganho de sobrevida clinicamente significativo em tumores específicos, a exemplo do anticorpo anti-HER2 trastuzumabe para câncer de mama com ERBB2 (HER2) amplificado, assim como os inibidores de EGFR para câncer de pulmão não pequenas células. No outro extremo, o último nível da escala trata de mutações que não têm base de evidências suficientemente robustas para amparar sua utilização como alvo terapêutico, e não devem ser consideradas para decisões clínicas.

“À medida que as evidências se acumulam, esperamos que alguns alvos se movam de um nível para outro”, sustentam os autores, que também reconhecem a importância crítica de validar qualquer teste genômico utilizado na clínica.

Para o oncologista Auro Del Giglio, a escala é plenamente aplicável ao contexto brasileiro. “Deveríamos ter aprovação e inclusão no rol da ANS dos níveis I e II, pelo menos. Acredito que isto permitiria acesso baseado em evidências sólidas de eficácia a terapias alvo-direcionadas para nossos pacientes do SUS e privados”, analisa Del Giglio, que defende a utilização da ESCAT também como referência aos testes genômicos. “Acho também que esta classificação deveria ser integrada aos laudos de perfilamento gênico de tumores em todas as plataformas, para orientação clínica”, conclui.


    ESCAT evidence tier Required level of evidence Clinical value class Clinical implication
   Ready for routine use I: Alteration-drug match is associated with improved outcome in clinical trials I-A: prospective, randomised clinical trials show the alteration-drug match in a specific tumour type results in a clinically meaningful improvement of a survival end point Drug administered to patients with the specific molecular alteration has led to improved clinical outcome in prospective clinical trial(s) Access to the treatment should be considered standard of care
  I-B: prospective, non-randomised clinical trials show that the alteration-drug match in a specific tumour type, results in clinically meaningful benefit as defined by ESMO MCBS 1.1
  I-C: clinical trials across tumour types or basket clinical trials show clinical benefit associated with the alteration-drug match, with similar benefit observed across tumour types
  Investigational II: alteration-drug match is associated with antitumour activity, but magnitude of benefit is unknown II-A: retrospective studies show patients with the specific alteration in a specific tumour type experience clinically meaningful benefit with matched drug compared with alteration-negative patients Drug administered to a molecularly defined patient population is likely to result in clinical benefit in a given tumour type, but additional data are needed Treatment to be considered ‘preferable’ in the context of evidence collection either as a prospective registry or as a prospective clinical trial
  II-B: prospective clinical trial(s) show the alteration-drug match in a specific tumour type results in increased responsiveness when treated with a matched drug, however, no data currently available on survival end points
  Hypothetical target III: alteration-drug match suspected to improve outcome based on clinical trial data in other tumour type(s) or with similar molecular alteration III-A: clinical benefit demonstrated in patients with the specific alteration (as tiers I and II above) but in a different tumour type. Limited/ absence of clinical evidence available for the patient-specific cancer type or broadly across cancer types Drug previously shown to benefit the molecularly defined subset in another tumour type (or with a diferente mutation in the same gene), efficacy therefore is anticipated for but not proved Clinical trials to be discussed with patients
  III-B: an alteration that has a similar predicted functional impact as an already studied tier I abnormality in the same gene or pathway, but does not have associated supportive clinical data
  IV: pre-clinical evidence of actionability IV-A: evidence that the alteration or a functionally similar alteration influences drug sensitivity in preclinical in vitro or in vivo models Actionability is predicted based on preclinical studies, no conclusive clinical data available Treatment should ‘only be considered’ in the context of early clinical trials. Lack of clinical data should be stressed to patients
  IV-B: actionability predicted in silico
  Combination development V: alteration-drug match is associated with objective response, but without clinically meaningful benefit Prospective studies show that targeted therapy is associated with objective responses, but this does not lead to improved outcome Drug is active but does not prolong PFS or OS, probably in part due to mechanisms of adaptation Clinical trials assessing drug combination strategies could be considered
  VI: lack of evidence for actionability No evidence that the genomic alteration is therapeutically actionable There is no evidence, clinical or preclinical, that a genomic alteration is a potential therapeutic target The finding should not be taken into account for clinical decision
           

















































































































Referências:

J Mateo, D Chakravarty, R Dienstmann, S Jezdic, A Gonzalez-Perez, N Lopez-Bigas, C K Y Ng, P L Bedard, G Tortora, J-Y Douillard, E M Van Allen, N Schultz, C Swanton, F André, L Pusztai; A framework to rank genomic alterations as targets for cancer precision medicine: the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT), Annals of Oncology, , mdy263, https://doi.org/10.1093/annonc/mdy263


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