Abstract 99P
Background
Fibroblast activation protein alpha (FAP) is expressed in several types of tumors and FAP-targeted radioligands are emerging in diagnostic and therapeutic (theranostic) approaches. We report on the expression pattern of FAP in solitary fibrous tumor (SFT) and its potential as radiotheranostic target.
Methods
We analyzed FAP mRNA expression and protein expression in SFT samples using immunohistochemistry (IHC) and multiplex immunofluorescence. Tracer uptake and detection efficacy were assessed in patients undergoing clinical 68Ga-FAPI-46 and 18F-FDG PET. 90Y-FAPI-46 radioligand therapy was offered to patients with progressive SFT and tumor response was evaluated.
Results
Among 813 patients, representing 126 tumor entities, from the prospective observational MASTER trial of the National Center for Tumor Disease and the German Cancer Consortium, SFT samples (n=34) showed the highest median FAP mRNA expression. Protein expression was confirmed in 30 of 38 (79%) SFT samples of an independent cohort; most samples showed intermediate to high FAP expression by IHC (25 of 38 samples, 66%), which was primarily located on the tumor cell surface. Nineteen patients who underwent 68Ga-FAPI-46 PET/CT imaging demonstrated higher tumor uptake (SUVmax 13.2, IQR 10.2) compared to 18F-FDG findings (3.2, IQR 3.1). 68Ga-FAPI-46 PET/CT also demonstrated higher detection efficacy with 367 detected tumor lesions in 68Ga-FAPI-46 PET/CT, 338 in contrast enhanced CT and 262 in 18F-FDG PET/CT. Eleven patients received a total of 34 cycles (median 3; IQR 2) 90Y-FAPI-46 radioligand therapy, which led to disease control in six cases and median progression free survival of 403 days.
Conclusions
In this translational study, we identified FAP as suitable theranostic target in SFT and demonstrate feasibility of FAP-directed imaging and therapy in a case series of SFT.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
R.W. Hamacher: Financial Interests, Personal, Other, Travel grant: Lilly, Novartis, PharmaMar; Financial Interests, Personal, Invited Speaker: PharmaMar, Lilly; Financial Interests, Personal, Advisory Board: PharmaMar; Financial Interests, Personal, Funding: Deutsche Forschungsgemeinschaft (DFG). P.F. Cheung: Financial Interests, Personal and Institutional, Invited Speaker: Deutsche Forschungsgemeinschaft (DFG). B.M. Schaarschmidt: Financial Interests, Personal and Institutional, Funding: PharmaCept. M.H.H. Schuler: Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Merck Serono, Novartis, Sanofi, Takeda; Financial Interests, Personal, Invited Speaker: Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, MSD, Novartis, Roche, Sanofi; Financial Interests, Institutional, Funding: AstraZeneca, Bristol Myers Squibb. S. Bauer: Financial Interests, Personal, Advisory Board, Recurring Advisory Role since 2017 in the context of clinical trial development: Deciphera; Financial Interests, Personal, Advisory Board, Advisory role in the context of clinical trial development: Blueprint Medicines; Financial Interests, Personal, Advisory Board, Advisory role for clinical trial development: Lilly; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board, Clinical trial development: Daiichi Sankyo; Financial Interests, Personal, Advisory Board, 2017: Plexxikon; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker, CME-related presentations: PharmaMar; Financial Interests, Personal, Advisory Board, Advisory role drug development: Roche, Exelixis; Financial Interests, Personal, Advisory Board, Advisory role drug development: GSK; Financial Interests, Personal, Advisory Board, Advisory Board Drug Development: Adcendo; Financial Interests, Personal, Advisory Board, Drug development: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Invited Speaker, PI for Enliven trial: Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker, Local PI for Avelumab phase I trial: Roche; Financial Interests, Institutional, Invited Speaker, PI for Intrigue, Invictus and DCC-2618-phase I trial and Vimseltinib-phase III; Lead PI for INtrigue trial, Scientific Committee for Invictus and Intrigue: Deciphera; Financial Interests, Institutional, Invited Speaker, PI for JGDJ trial phase I Olaratumab plus Doxo/Ifos: Lilly; Financial Interests, Institutional, Invited Speaker, PI for phase I trials cCGM097, HDM201, STI571-2103: Novartis; Financial Interests, Institutional, Invited Speaker, Local PI und national PI for Voyager and Navigator trial (BLU-285 / Avapritinib): Blueprint Medicines; Financial Interests, Institutional, Invited Speaker, PI (national) for Relatlimab (BMS-CA224-020): BMS; Financial Interests, Institutional, Invited Speaker, PI for IIT with ponatinib in GIST; Research Grant (institutional for IIT): Incyte; Non-Financial Interests, Personal, Advisory Role, Off-label committee (until 2021); External consultant 2022: BfArm; Non-Financial Interests, Personal, Invited Speaker, Founding Member of German Sarcoma Foundation: Deutsche Sarkomstiftung (German Sarcoma Foundation). S. Fröhling: Financial Interests, Personal, Advisory Board: Bayer, Illumina, Roche; Financial Interests, Personal, Invited Speaker: Amgen, Eli Lilly, Illumina, PharmaMar, Roche. K. Herrmann: Financial Interests, Personal, Advisory Board: Bayer, Adacap/Novartis, Curium, Boston Scientific, GE Healthcare, AstraZeneca; Financial Interests, Personal, Invited Speaker: Sirtex, Siemens Healthineers, Monrol, Sofie Biosciences, Theragnostics, Pharma 15; Financial Interests, Personal, Other, Consultant: Amgen; Financial Interests, Personal, Other, DMSB: Ymabs; Financial Interests, Personal, Advisory Board, Scientific Advisor: AdvanceCell; Financial Interests, Personal, Advisory Board, Advisor, Consultant: Janssen; Financial Interests, Personal, Advisory Board, Consultant: Eco1R; Financial Interests, Personal, Ownership Interest: Sofie Biosciences; Financial Interests, Personal, Stocks/Shares: Aktis Oncology; Non-Financial Interests, Personal, Leadership Role, Chair Oncology & Theragnostics Committee: EANM. J. Siveke: Financial Interests, Personal, Advisory Role: AstraZeneca, Bayer, Immunocore, Roche, Servier; Financial Interests, Institutional, Funding: Bristol Myers Squibb, Celgene, Roche; Financial Interests, Personal, Ownership Interest: Pharma15; Financial Interests, Personal, Member of the Board of Directors: Pharma15. H. Schildhaus: Financial Interests, Institutional, Advisory Board: MSD, BMS, Novartis; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Roche, Takeda, Agilent, ZytoVision; Financial Interests, Personal, Full or part-time Employment: Targos/DLS Inc.; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Funding: Blueprint Medicines; Other, Personal, Other, Member of the QuIP Board (Quality Assurance Organisation): QuIP GmbH. W. Fendler: Financial Interests, Personal, Funding: SOFIE Bioscience, Bayer; Financial Interests, Personal, Invited Speaker: Janssen, Bayer, Novartis, Telix; Financial Interests, Personal, Advisory Role: Janssen, Calyx, Bayer; Financial Interests, Personal, Other, image review: Parexel. All other authors have declared no conflicts of interest.