1930O - Genomic alterations in solid tumours according to ESMO scale for clinical actionability of molecular targets (ESCAT)

Background

Comprehensive genomic profiling (CGP) in advanced solid tumors has led to implement precision medicine in clinical practice. However, genomic alterations (GAs) detected are still not routinely used for therapeutic decision in the majority of the tumor types. The ESMO ESCAT ranks the GAs based on their clinical actionability. Since 2018, our Molecular Tumor Board (MTB) stratified the GAs detected in tissue/liquid biopsy based on ESCAT to guide treatment selection. Based on ESCAT, we aimed to assess clinical actionability of GAs through our MTB.

Methods

Patients (pts) with metastatic solid tumors enrolled in MOSCATO (NCT01566019) and MATCHR (NCT02517892) trials underwent a tumor biopsy at time of relapse. Molecular profiling was performed using next-generation sequencing (NGS), whole-exome sequencing and RNA-sequencing. Clinical actionability of GAs was prospectively assessed at our MTB according to ESCAT tiers. Clinical characteristics and outcome of pts were also collected.

Results

Between Nov 2018 and March 2020, 387 pts underwent a biopsy. Molecular data from 366 pts were interpreted at the MTB. Median age was 61 (range, 24-90); 221 pts (60%) were male. Twenty-seven different tumor types were discussed; the most common were lung (n=117, 32%), gastrointestinal (n=105, 28%) and urological cancer (n=60; 16%). At least one GA was detected in 94% (366/388; 5% failed analysis). Based on ESCAT, GAs were classified according to the tumor type: 20% were tier I [N=72: 25 EGFR mutation (m), 6 ALK rearrangement (r); 6 FGFRr, 4 BRAFV600Em; 9 RETr, 9 RETm; 5 MSI-H; 3 ROS1r; 2 HER2a; 2 BRCAm; 1 METm]; 7% as tier II (n=25: 19 KRASG12Cm; 3 BRAFV600Em [other than lung/melanoma]; 2 METa; 2 HERm); 19% as tier III (n=48) and 16% as tier IV (n=59). Based on ESCAT, CGP reported clinically informative results in 117 pts (32%) and guiding treatment selection in 73 pts (20%). Clinical outcomes (progression free survival; response rate) by ESCAT tier will be presented during the meeting.

Conclusions

ESCAT classification of genomic alterations is attainable in clinical practice through MTB and helps adjusting treatment on both standard of care or investigational settings. Since ESCAT tiers update regularly, a dynamic review of therapeutic choices is advised.

Legal entity responsible for the study

Gustave Roussy.

Funding

Gustave Roussy.

Disclosure

P. Martin Romano: Research grant/Funding (institution): BMS; Research grant/Funding (institution): Astrazeneca. L. Mezquita: Advisory/Consultancy, Speaker Bureau/Expert testimony: Bristol-Myers Squibb. L. Lacroix: Research grant/Funding (institution): AstraZeneca. A. Varga: Research grant/Funding (self), Research grant/Funding (institution): AstraZeneca. C. Baldini: Advisory/Consultancy: Bristol-Myers Squibb. S. Postel-Vinay: Research grant/Funding (self), Research grant/Funding (institution): Boehringer Ingelheim; Travel/Accommodation/Expenses: AstraZeneca. L. Friboulet: Travel/Accommodation/Expenses: AstraZeneca. A. Gazzah: Research grant/Funding (institution), Non-remunerated activity/ies, Principal/sub-Investigator: AstraZeneca. J-C. Soria: Shareholder/Stockholder/Stock options: AstraZeneca. A. Hollebecque: Research grant/Funding (institution), Non-remunerated activity/ies: Bristol-Myers Squibb. B. Besse: Research grant/Funding (institution), Non-remunerated activity/ies: Boehringer Ingelheim. C. Massard: Research grant/Funding (institution), Non-remunerated activity/ies: Principal/sub-Investigator; Research grant/Funding (institution): Research Grants; Non-remunerated activity/ies: Non-financial support (drug supplied). A. Italiano: Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy: Epizyme; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy: Philips; Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy: Springworks; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Merck; Research grant/Funding (institution): PharmaMar. All other authors have declared no conflicts of interest.