115P - Gene rearrangements, actionability and access to precision medicine: Results from the ARCAGEN study

Background

Rare cancers (defined by an incidence <6/10⁵/y) have more often inaccurate diagnoses, molecular profiling and access to clinical trials. Within the EORTC-SPECTA platform, the ARCAGEN study conducted between EORTC and EURACAN was initiated in 2019 and aimed to assess the prevalence of genomic alterations, and their actionability in patients diagnosed with advanced rare cancers.

Methods

Patients with a rare adult solid tumor of one of the 10 domains of EURACAN in advanced phase were molecularly characterized (F1LCDx, F1HemeCDx or F1CDx) in the ARCAEN study as part of the SPECTA program after signing the informed consent.

Results

Within 3.5 years, 918 patients were recruited within 14 countries in Europe and evaluable. Rearrangements (including inversions and fusions) were identified in 166 patients (18%), clinically significant in 102 (11%) patients and actionable for 55 (6%). Actionable alterations were predominantly identified in FGFR2 (n=17), EGFR (n=6), ALK (n=4) and NTRK (n=2), and in patients with rare sarcoma (10 out of 66, 15%, mainly diagnostic fusions), brain (8 out of 63, 12.7%) and GI malignancies (12 out of 119, 10%). Personalized therapy was adopted for 11 out of 55 patients (20%, including 5 cholangiocarcinoma and 2 thyroid cancers), with 8 (73%) partial responses, 3 (27%) SD, for a median PFS of 12 months (range [2-24 months]) and 4 patients still on treatment at time of analysis, including 3 for longer than 15 months with RET or ALK fusion. 25 patients (45%) with actionable alterations died before accessing the recommended therapy.

Conclusions

Rearrangements in rare cancers have at least, a similar rate as in common cancers and can be targeted. However, despite identification of the alterations, treatment access remains limited.

Clinical trial identification

SPECTA - NCT02834884.

Editorial acknowledgement

Legal entity responsible for the study

European Organisation of Research and Treatment of Cancer.

Funding

Cencora, Hoffman-La Roche.

Disclosure

N. Penel: Financial Interests, Institutional, Research Grant, Research grant for clinical trials in sarcoma filed: Bayer HealthCare. L.F.L. Licitra: Financial Interests, Personal, Advisory Board, for expert opinion in advisory boards: AstraZeneca, Bayer, BMS, Eisai, MSD, Boehringer Ingelheim, Hoffmann-La Roche Ltd, Novartis, Roche, Debiopharm International SA, Sobi, Incyte Biosciences Italy srl, Doxa Pharma srl, Amgen, Nanobiotics, GSK; Financial Interests, Institutional, Research Grant, Funds received by my institution for clinical studies and research activities in which I am involved: AstraZeneca, BMS, Boehringer Ingelheim, Celgene International, Eisai, Exelixis, Debiopharm International SA, Hoffmann-La Roche ltd, IRX Therapeutics, Medpace, Merck–Serono, Merck Healthcare KGaA, MSD, Novartis, Pfizer, Roche, Adlai Nortye. N. Girard: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Pfizer, Mirati, Amgen, Novartis, Sanofi, Gilead; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Boehringer Ingelheim, Novartis, Sanofi, AbbVie, Amgen, Lilly, Grunenthal, Takeda, Owkin, Leo Pharma, Daiichi Sankyo, Ipsen; Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen; Financial Interests, Institutional, Funding: BMS, Leo Pharma; Financial Interests, Institutional, Research Grant: MSD; Other, Family member is an employee: AstraZeneca. J.A. Gietema: Financial Interests, Institutional, Research Grant, Research grant paid to the institution UMCG: Roche, Siemens, AbbVie. W.W. de Herder: Financial Interests, Personal, Advisory Board: Novartis, Ipsen, ITM; Financial Interests, Personal, Invited Speaker: Novartis; Non-Financial Interests, Leadership Role, Chairman EURACAN Domain 4 Rare Cancer of the Neuroendocrine system: EU. E. Kapiteijn: Financial Interests, Institutional, Advisory Board: Delcath, Lilly; Financial Interests, Institutional, Invited Speaker: Immunocore; Financial Interests, Institutional, Coordinating PI: BMS, Pierre-Fabre, Delcath, Novartis. I.L. Ray-Coquard: Financial Interests, Personal, Advisory Board: Roche, GSK, AstraZeneca, Mersana, Deciphera, Amgen, Oxnea, Merck Sereno, Agenus, Novartis, Macrogenics, Clovis, EQRX, adaptimmun, Eisai, SUTRO, BMS, Adaptimmune, Daiichi Sankyo, Immunogen, Seagen, PMVpharma; Financial Interests, Institutional, Other, Colibri translational research: BMS; Financial Interests, Institutional, Advisory Board, translational research NEOPREMBROV trial: MSD; Non-Financial Interests, Principal Investigator: PAOLA1; Non-Financial Interests, Other, President: Gineco. J. Blay: Financial Interests, Institutional, Invited Speaker: MSD, MSD, PharmaMar; Financial Interests, Institutional, Advisory Board: Bayer, GSK, Roche; Financial Interests, Personal, Advisory Board: Deciphera; Financial Interests, Personal, Other, member of the supervisory board. No remunerations in 2021 and 2022.: Innate pharma; Financial Interests, Personal, Member of Board of Directors: Transgene; Financial Interests, Institutional, Funding: MSD, BMS, Deciphera; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Bayer, GSK, Novartis, OSE pharma. All other authors have declared no conflicts of interest.