Abstract 548P
Background
Genetic profiling (GP) might help identify potential targets for targeted therapies. At the same time, selected CT offer comprehensive gene panel testing during the pre-screening phase. Here, we have studied our experience using these panels.
Methods
We selected 14 CT from our Early Drug Development Clinical Trial Unit at Hospital Clinic of Barcelona that included analysis of gene panels in tumor (Foundation One, ArcherDX, Therascreen and Sophia Genetics) or plasma (Resolution Bioscience ctDx). These panels analyzed mutations, fusions, amplifications, microsatellite instability (MSI) and tumor mutational burden (TMB), among others. We collected information about types of cancers, molecular alterations and therapies chosen according to the results of GP. Descriptive statistics were used.
Results
From March 2017 to April 2020 we analyzed 286 samples from 257 patients (pts) with urothelial (26.8%), prostate (25.3%), CNS (18.3%), ovarian (8.6%), colorectal (5.1%), breast (4.7%), endometrial (2.7%), esophagogastric (2.7%), pancreatic (1.9%), cervix (1.2%), HNSCC (0.8%), cholangiocarcinoma (0.8%), renal (0.4%), fallopian tube (0.4%) and paraganglioma (0.4%). 205 pts (79.8%) had ≥ 1 genetic alteration. The most frequently altered genes were TP53 (92 pts, 55.1%), TERT (52 pts, 28.9%), MLL3 (4 pts, 28.3%), SPTA1 (3 pts, 21.4%), CDKN2A (34 pts, 21.1%), PTEN (33 pts, 20.5%), CDKN2B (27 pts, 20.1%), ATM (40 pts, 19.6%) and MLL2 (26 pts, 19.5%). TMB ranged from 0 to 12.61 mut/Mb. MSI was found in 2 pts (2.5%). 23 pts (9%) received a matched therapy (Table): 12 pts (52.1%) were included in the same CT for which the pre-screening was performed, 7 pts (30.4%) were included in a different CT, and 4 pts (17.3%) received an off-label matched drug. Table: 548P
Cancer type | Molecular alteration | Treatment administered |
Urothelial | FGFR3 | Erdafitinib |
FGFR3 | Erdafitinib + Cetrelimab | |
FGFR3 | Pemigatinib | |
ERBB2 and FGFR3 | Afatinib → B-701 | |
FGFR3 | Vofatamab | |
ERBB2 | Afatinib | |
FGFR3 | B-701 | |
Prostate | ATM | Niraparib |
BRCA2 | Olaparib | |
BRCA2 | Rucaparib | |
BRCA2 | Niraparib | |
CNS | EGFR | Depatuximab |
EGFR | Depatuximab | |
EGFR | AMG 596 | |
Colorectal | RAD51D | Olaparib + Pembrolizumab |
ATM | Olaparib + Pembrolizumab | |
CHEK2 | Olaparib + Pembrolizumab | |
Ovarian | BRCA1 | Rucaparib |
BRCA1 | Rucaparib | |
BRCA1 | Olaparib | |
Endometrial | MSI-H | Pembrolizumab |
Pancreatic | ATM and MSI | Olaparib + Pembrolizumab |
Paraganglioma | NTRK1 | Entrectinib → LOXO195 |
Conclusions
Comprehensive gene panel testing offered through CT allow the identification of molecular targets and the possibility to recruit. However, the possibility for a patient to enter a CT with a matched therapy was <10%.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
B. Mellado Gonzalez: Honoraria (self), Research grant/Funding (self): Astellas; Honoraria (self), Research grant/Funding (self), Non-remunerated activity/ies: Jansen; Honoraria (self), Research grant/Funding (self), Non-remunerated activity/ies: Sanofi; Honoraria (self), Research grant/Funding (self), Non-remunerated activity/ies: Roche; Non-remunerated activity/ies: BMS; Honoraria (self), Non-remunerated activity/ies: Merck; Honoraria (self), Non-remunerated activity/ies: Pfizer; Research grant/Funding (self): Bayer. E. Pineda: Speaker Bureau/Expert testimony: Sanofi; Advisory/Consultancy: Amgen. L. Gaba: Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZenca; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Tesaro; Advisory/Consultancy, Speaker Bureau/Expert testimony: GSK. L. Ferrer Mileo: Honoraria (self): Pfizer; Honoraria (self): Kyowa Kirin. J. Maurel: Advisory/Consultancy: Sirtex; Advisory/Consultancy: Servier; Advisory/Consultancy: Pierre-Fabre; Advisory/Consultancy: Advance Medical; Advisory/Consultancy: Shire; Advisory/Consultancy: AstraZenca; Advisory/Consultancy: Bayer; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Roche. O. Martinez Saez: Speaker Bureau/Expert testimony: Eisai. N. Chic: Speaker Bureau/Expert testimony: Eisai. N. Baste: Advisory/Consultancy: Merck; Advisory/Consultancy: BioNtech; Advisory/Consultancy: Nanobiotix; Advisory/Consultancy: BMS; Speaker Bureau/Expert testimony: MSD; Speaker Bureau/Expert testimony: AstraZenca; Speaker Bureau/Expert testimony: Eisai. N. Vinolas Segarra: Advisory/Consultancy: Roche; Advisory/Consultancy: Boeringher Ingelheim; Advisory/Consultancy: Pierre-Fabre; Advisory/Consultancy: BMS; Advisory/Consultancy: Pfizer; Advisory/Consultancy: MSD; Advisory/Consultancy: Lilly; Advisory/Consultancy: AstraZenca. A. Prat: Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Amgen; Speaker Bureau/Expert testimony: BMS; Speaker Bureau/Expert testimony: Daiichi Sankyo; Advisory/Consultancy: Puma; Advisory/Consultancy: Oncolytics Biotech; Advisory/Consultancy: MSD; Advisory/Consultancy: Lilly; Speaker Bureau/Expert testimony: Nanostring technologies. J. Garcia-Corbacho: Speaker Bureau/Expert testimony: Bayer; Advisory/Consultancy: SOLTI; Travel/Accommodation/Expenses, ASCO2020 conference registration: BMS. All other authors have declared no conflicts of interest.