New molecular target classification system could aid treatment decision making
medwireNews: The ESMO Translational Research and Precision Medicine Working Group has proposed a classification system that orders the value of molecular aberrations as oncologic clinical targets based on the supporting evidence available.
“This clinical benefit-centred classification system offers a common language for all the actors involved in clinical cancer drug development. Its implementation in sequencing reports, tumour boards and scientific communication, can enable precise treatment decisions and facilitate discussions with patients about novel therapeutic options,” say Fabrice Andre (ESMO Head Office – Scientific Affairs, Lugano, Switzerland) and fellow authors.
They have graded the molecular targets into six tiers according to their implications for patient management to produce The ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT).
Tier I includes targets that are ready for implementation in routine clinical decisions, such as the anti-HER2 antibodies, including trastuzumab, for HER2-amplified breast cancer and EGFR inhibitors for non-small-cell lung cancer patients harboring an EGFR activating mutation.
Tier II is for investigational targets where benefit has been shown in a molecularly defined patient population but more data is needed. These include the PI3K–PTEN pathway, which has been targeted by AKT inhibition with ipatasertib in patients with advanced prostate cancer.
Tier III is for targets where clinical benefit has been demonstrated in other tumor types, for example B-Raf enzyme inhibition with vemurafenib, which significantly extends survival in patients with metastatic melanomas harboring the BRAF V600E mutation but has variable activity in other tumors. Tier III also includes targets for which clinical benefit has been shown for similar molecules, such as the germline BRCA1 or BRCA2 mutations, which are Tier I targets in breast and ovarian cancers but are Tier III for prostate and pancreatic cancers.
Tier IV is for targets where there is preclinical evidence of action. And Tier V is for targets where evidence of action is lacking, but there may still be potential in combination therapy strategies.
“Clear terminology regarding clinical utility should decrease the chance for misinterpretation of results that could lead to missed opportunities for effective treatment or over-interpretation of hypothetical targets,” the group concludes in the Annals of Oncology.
By Lucy Piper
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