New Scale Grades Mutations, Optimizing Targeted Cancer Therapy

Roxanne Nelson, BSN, RN

August 28, 2018

A new scale for tumor DNA mutations that aims to simplify and standardize the choice of targeted therapies has been introduced by the European Society for Medical Oncology (ESMO).

Known as ESCAT (ESMO Scale for Clinical Actionability of Molecular Targets), the goal of the scale is to improve patient care by optimizing the selection of those patients most likely to respond to precision medicines, which in turn will make the treatment more cost effective.

"Doctors receive a growing amount of information about the genetic makeup of each patient's cancer, but this can be difficult to interpret for making optimal treatment choices," said Fabrice André, MD, PhD, chair of the ESMO Translational Research and Precision Medicine Working Group, which initiated this project.

"The new scale will help us distinguish between alterations in tumor DNA that are important for decisions about targeted medicines or access to clinical trials and those which aren't relevant," Andre explained in a statement.

Details were published online August 21 in the Annals of Oncology.

The new grading system categorizes alterations in tumor DNA according to their relevance as markers for selecting patients for targeted treatment. The system uses "tiers" based on the strength of supporting clinical evidence. This is the first time that a classification system has been developed that is relevant to all potential targeted oncology therapeutics and is not limited to those approved for use by national regulatory bodies. The classification also enables mutations to be upgraded or downgraded as new data emerge.

The Tier Scale

The new scale categorizes mutations as follows:

  • Tier I: The target is suitable for routine use, and the recommendation is for a specific drug when specific molecular alteration is detected. Examples include HER2 in breast cancer; BRCA1/2 in breast and ovarian cancers; ROS1/ALK in non–small cell lung cancer; TRK and PD1 in multiple cancers; and BRAF in metastatic melanoma.

  • Tier II: These are investigational targets likely to identify patients who would benefit from a targeted drug, but additional data are needed. Examples include the PTEN pathway (PIK3CA, AKT1).

  • Tier III: These targets have been previously demonstrated to be of clinical benefit in other tumor types or for related molecular targets. Examples include BRAF in nonmelanoma cancers and PALB2 and other non-BRCA DNA repair mutations.

  • Tier IV: For the targets in this tier, there is preclinical evidence of actionability. These targets are hypothetical and are considered as warranting future clinical testing.

  • Tier V: For these targets, there is evidence of relevant antitumor activity not resulting in meaningful clinical benefit as single treatment but that supports development of cotargeting approaches. Examples include PIK3CA in ER+ and HER- breast cancer.

  • Tier X: These targets lack of evidence for actionability. These are DNA alterations for which there is no clinical or preclinical evidence supporting their hypothetical utility as therapeutic targets and should not be taken into account for clinical decisions.

Ready for Routine Use

"The scale focuses on the clinical evidence for matching tumor mutations with the drugs we have in our clinics and gives us a common vocabulary for communication between clinicians and for explaining potential treatment benefits to patients," said Joaquin Mateo, MD, lead author of the article and principal investigator of the Prostate Cancer Translational Research Group from the Vall d'Hebron Institute of Oncology, Barcelona, Spain, in a statement.

The authors note that as ESCAT is disseminated into clinical practice, it is hoped that cancer centers and laboratories will begin to routinely include Tier I-V grading of genomic mutations in clinical and laboratory reports.

"If one mutation is Tier I and another is Tier III, it is important that everyone understands the need to prioritize the Tier I mutation in determining the patient's treatment and implementing precision medicine," Mateo noted.

The ESCAT project is funded by ESMO. Several of the authors have disclosed relationships with industry, as detailed in the original article.

Ann Oncol. Published online August 21, 2018. Full text


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: