Targetable genomic alterations (GAs) that are detected by comprehensive genomic profiling (CGP) in advanced solid tumours and stratified according to ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) can be used to guide treatment decisions in clinical practice, according to findings presented by Patricia Martin Romano of the DITEP, Gustave Roussy in Villejuif, France at the ESMO Virtual Congress 2020.
She explained that CGP of advanced solid tumours has yielded information to guide precision medicine in clinical practice. Additional therapeutic information is provided by the ESMO ESCAT, which ranks the GAs based on their clinical actionability.
The Molecular Tumour Board (MTB) at the Institute Gustave Roussy has evaluated the GAs detected in tissue and liquid biopsies based upon ESCAT to determine treatment since 2018. This study, conducted by professor Romano and colleagues, assessed the clinical actionability of GAs based on ESCAT stratification by the MTB.
Data were used for this analysis from 387 patients with metastatic solid tumours participating in the MOSCATO and MATCHR studies that also underwent tumour biopsy at the time of relapse. Molecular profiling was performed using next-generation sequencing, whole-exome sequencing, and RNA-sequencing to identify actionable GAs. The clinical actionability of GAs was prospectively assessed by the MTB according to ESCAT tiers. Clinical characteristics and outcome of patients were also collected.
ESCAT-based tiers of actionable GAs led to treatment selection in 20% of patients
Of the 387 patients providing biopsy samples from November 2018 to March 2020, molecular data from 366 patients were interpreted at the MTB. The median age of the patients was 61 (range, 24 to 90) years and 221 (60%) patients were male.
At least one GA was detected in 366 of 388 (94%) samples, with a rate of just 5% failed analysis.
The MTB discussed 27 different tumour types; the most common types were 117 (32%) lung, 105 (28%) gastrointestinal, and 60 (16%) urological cancer.
Based on ESCAT, GAs were classified according to the tumour type; of these 72 (20%) were tier I including 25 EGFR mutation, 6 ALK rearrangement, 6 FGFR rearrangement, 4 BRAFV600E mutation, 9 RET rearrangement, 9 RET mutation, 5 microsatellite–high (MSI-H) 3 ROS1 rearrangement, 2 HER2 alteration, 2 BRCA mutation, and 1 MET mutation.
Twenty-five (7%) GAs were classified as tier II including 19 KRASG12C mutation, 3 BRAFV600E mutation (other than lung or melanoma) 2 MET alteration, 2 HER mutation. Forty-eight (19%) GAs were classified as tier III and 59 (16%) as tier IV.
Based on ESCAT, CGP reported clinically informative results for 117 (32%) patients that led to treatment selection in 73 (20%) patients.
The clinical outcomes including progression-free survival and response rate according to ESCAT tier were presented during the meeting.
The authors concluded that ESCAT classification of genomic alterations is feasible in clinical practice through MTB evaluation and helps in adjusting treatment in both standard of care and investigational settings. They advise a dynamic review of therapeutic choices according ESCAT tiers updates.
1930O - Martin Romano P, Mezquita L, Lacroix L, et al. Genomic alterations in solid tumors according to ESMO Scale for Clinical Actionability of molecular Targets (ESCAT). ESMO Virtual Congress 2020.