Abstract 102P
Background
The rapid and widespread implementation of comprehensive genomic profiling programmes in oncology raised questions regarding clinical utility. There are uncertainties surrounding the identification and therapeutic implications of actionable mutations. Despite available data suggesting that >40% of patients profiled exhibit at least one actionable mutation, access to target therapies is a relevant potential roadblock to the progression of precision oncology.
Methods
FPG500 (IRB approval 3837; NCT06020625) is an interventional monocentric prospective study enrolling selected cancer patients for comprehensive cancer genome profiling (CGP). When feasible, sequencing is performed with the TruSight Oncology 500 high throughput assay (TSO500HT, Illumina). The assay, internally validated, identifies single nucleotide variants (SNVs), insertions/deletions (indels), copy number variations (CNVs), fusions and splicing variants in 523 and 55 genes for DNA and RNA, respectively. Molecular findings are reported according to the European Society of Medical Oncology Scale for Clinical Actionability of molecular Targets (ESCAT) recommendations.
Results
From January 2022 to June 2023, 2230 patients have been profiled. CGP was feasible in 85% of patients. Overall, 51% of patients were shown to have at least one actionable genomic alteration according to the ESCAT classification (level I, II, III, IV). The rate of patients with level I actionable genomic alterations was 52% while 48% had level II/III/IV genomic alterations (Table 102P). Table: 102P
Actionable genomic alterations (*Level I alterations)
| GENE | Breast | Biliary tract | Colorectum | Uterus | GIST | Lung | Melanoma | Ovary | Pancreas | Prostate | Thyroid | Total |
| ALKr | 0 | 0 | 0 | 0 | 0 | 24* | 0 | 2 | 0 | 0 | 0 | 26 |
| BRAF | 0 | 2 | 25* | 6 | 0 | 30* | 24* | 14 | 1 | 1 | 3 | 106 |
| BRCA1 | 1* | 1 | 5 | 10 | 0 | 9 | 1 | 136* | 1* | 3* | 0 | 167 |
| BRCA2 | 1* | 1 | 5 | 25 | 0 | 23 | 1 | 59* | 5* | 6* | 0 | 126 |
| EGFR | 1 | 2 | 13 | 3 | 0 | 91* | 0 | 11 | 9 | 0 | 0 | 130 |
| ERBB2 | 4* | 5 | 15 | 18 | 0 | 17* | 1 | 14 | 4 | 0 | 0 | 78 |
| FGFR2r | 0 | 1* | 1 | 0 | 0 | 0 | 0 | 5 | 1 | 0 | 0 | 8 |
| IDH1 | 0 | 4* | 0 | 0 | 0 | 2 | 3 | 0 | 0 | 0 | 0 | 9 |
| KIT | 0 | 0 | 0 | 0 | 4* | 2 | 1 | 3 | 0 | 0 | 0 | 10 |
| KRAS | 1 | 13 | 155* | 73 | 0 | 123* | 0 | 66 | 108 | 1 | 1 | 541 |
| MET | 0 | 1 | 3 | 0 | 0 | 33* | 1 | 10 | 4 | 0 | 0 | 52 |
| METr | 0 | 1 | 0 | 0 | 0 | 24* | 1 | 0 | 0 | 0 | 0 | 26 |
| MLH1 | 0 | 0 | 2* | 11* | 0 | 1 | 0 | 3 | 1 | 1 | 0 | 19 |
| MSH2 | 0 | 0 | 1* | 27* | 0 | 0 | 0 | 2 | 0 | 1 | 0 | 31 |
| MSH6 | 0 | 0 | 2* | 22* | 0 | 1 | 0 | 11 | 2 | 0 | 0 | 38 |
| NTRK1r | 0 | 0 | 0 | 0 | 0 | 0 | 1* | 0 | 0 | 0 | 0 | 1 |
| NTRK3r | 0 | 0 | 1* | 0 | 0 | 2* | 0 | 0 | 0 | 0 | 0 | 3 |
| PDGFRα | 0 | 0 | 0 | 0 | 3* | 3 | 0 | 1 | 0 | 0 | 0 | 7 |
| PIK3CA | 3* | 0 | 45 | 196 | 0 | 30 | 2 | 96 | 3 | 3 | 2 | 380 |
| PMS2 | 0 | 0 | 0 | 2* | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 4 |
| RETr | 0 | 0 | 0 | 0 | 0 | 12* | 0 | 0 | 0 | 0 | 0 | 12 |
| ROS1r | 0 | 0 | 0 | 0 | 0 | 8* | 0 | 10 | 2 | 0 | 0 | 20 |
| Total | 11 | 31 | 273 | 393 | 7 | 435 | 36 | 445 | 141 | 16 | 6 | 1794 |
Conclusions
Our results support the role of extensive CGP as a tool for detecting targetable alterations thus potentially allowing patients‘ access to innovative treatments. Information on therapeutic choices following profiling and prognostic outcomes is currently being gathered.
Clinical trial identification
NCT06020625.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
C. Nero: Financial Interests, Personal, Other, Travel Support: Illumina, MSD; Financial Interests, Personal, Other, Honoraria: VEEVA, GSK, Altems. E. Bria: Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca, Pfizer, Novartis, Roche; Financial Interests, Personal, Other, Consultant: Pfizer. L. Salvatore: Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca, Bayer, Merck, Amgen. R. Iacovelli: Financial Interests, Personal, Advisory Board: Pfizer, Janssen, Sanofi, MSD, Novartis. A. Fagotti: Financial Interests, Personal, Research Grant: AstraZeneca, MSD; Financial Interests, Personal, Other, Consultant: J&J, Menarini. D. Lorusso: Financial Interests, Personal, Funding: Clovis, GSK, MSD, GenMab. G. Tortora: Financial Interests, Personal, Advisory Board: BMS, Novartis. N. Normanno: Financial Interests, Personal, Advisory Board: MSD, Bayer, Illumina; Financial Interests, Personal, Funding: Merck, ThermoFisher. G. Scambia: Financial Interests, Personal, Other, Honoraria: Clovis; Financial Interests, Personal, Other, Consultant: Tesaro, J&J. All other authors have declared no conflicts of interest.