132MO - Molecular profiling of 991 prospectively recruited rare cancers patients in EUROPE: First results of ARCAGEN – an EORTC-SPECTA and EURACAN study

Background

Within the EORTC-SPECTA platform, the ARCAGEN collaborative study between EORTC and EURACAN was initiated in June 2019 and aimed to assess the prevalence of genomic alterations, high tumor mutational burden (TMB) and microsatellite instability (MSI), as well as actionability in patients diagnosed with advanced rare cancers (defined with an incidence<6/10⁵/y).

Methods

Patients with a rare adult solid tumor of one of the 10 domains or EURACAN in advanced phase were proposed for the ARACAGEN study as part of the SPECTA program.

Results

Within 3.5 years, 991 patients were enrolled within 14 countries in Europe, 918 were evaluable, receiving a molecular profile (92.60% success rate), with a median turn-around time of 13.25 days [range 11.5-17]. Molecular profiling was preferentially performed on FFPE material (FoundationOne, 73.5%), if not feasible, liquid biopsy was used as a rescue (FoundationOne Liquid, 26.5%). The 3 most common histotypes were cancer of unknown primary (CUP, 103, 11.2%), mesothelioma (80, 8.7%), cholangiocarcinoma (72, 7.8%). Clinically relevant molecular alterations were identified in 606 patients (66%), with top alterations seen in TP53 (28.5% of all enrolled patients), CDKN2A/B (16.8%), KRAS (9.2%). The TMB was above 10 for 53 patients (5.3%) and 9 MSI-high patients were identified. A differential profile was seen between FFPE and blood analysis due to CHIP identification (DNMT3A, MLL2, TET2 for example). Altogether, 456 patients (46%) received a therapy recommendation based on the molecular analysis: 63 (6.8%) patients for an already approved treatment (ESCAT 1A); 232 (25.3%) for an off-label use of an approved treatment in another indication with similar molecular alteration (ESCAT IC, II or III); and 161 (17.5%) for a clinical trial. Response rate, duration of response and survival will be presented.

Conclusions

Close to 50% of patients with rare cancers received a therapeutic recommendation based on molecular characterization, a majority within clinical trials. Molecular characterization should be recommended routinely for rare cancers in advanced phase.

Clinical trial identification

SPECTA NCT02834884.

Editorial acknowledgement

Legal entity responsible for the study

EORTC.

Funding

Hoffman-La Roche.

Disclosure

M. Morfouace: Financial Interests, Personal, Other, Employee: Merck Healthcare. J. Oliveira: Financial Interests, Personal, Other, Advisory board, Invited Speaker: AstraZeneca, Roche, Novartis, Janssen; Financial Interests, Personal, Invited Speaker: GSK, BMS, MSD, Bayer; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Institutional, Funding, Investigator Initiated Clinical Trial funding: AstraZeneca. B. Brasiuniene: Financial Interests, Personal, Other, lecture, advisory board, publications, expert testimony; reimbursement of travel expenses: sia ; Financial Interests, Personal, Writing Engagement, editor work in the local journal: UAB; Financial Interests, Personal, Advisory Board, lecture - speaker, expert testimony; reimbursement of travel expenses: AstraZeneca Lietuva UAB; Financial Interests, Personal, Invited Speaker, lecture-speaker: Merck Serono UAB; Financial Interests, Personal, Advisory Board, lecture-speaker, writing engagement, expert testimony: ElI Lilly Lietuva UAB; Financial Interests, Personal, Advisory Board, Meeting, Conference, Scientific Programme Organization, Search for the Speakers, Chair of The Meeting, Speaker: Nacionalinis mokymų centras VŠĮ; Financial Interests, Personal, Invited Speaker, Lecture Presentation: Sevier pharma; Financial Interests, Personal, Invited Speaker, Invited Speaker, Writing Engagement: Baltmeda UAB; Financial Interests, Personal, Invited Speaker, Lecture, Speaker, Expert Testimony: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker, Invited Speaker (chair of the season): Esmo; Financial Interests, Personal, Invited Speaker: Medison Pharma Lithuania; Financial Interests, Personal, Local PI, working in clinical trials: Novartis Pharma AG; Financial Interests, Personal and Institutional, Coordinating PI, Working with Clinical Trial: EORTC; Financial Interests, Personal, Local PI, working with clinical trial: Ergomed, AstraZeneca Lietuva UAB; Financial Interests, Personal, Steering Committee Member, SC member for ENGOT-EN10 clinical trial DUO-E: AstraZeneca; Financial Interests, Personal and Institutional, Local PI, Work with Clinical Trial: Labcorp Drug development; Financial Interests, Personal and Institutional, Local PI, Work with Clinical Trials: NSGO, PSI CRO AG; Non-Financial Interests, Member: Lithuanian Society of Oncologist; Non-Financial Interests Member, Member of Gynecological Cancer Group and Melanoma Group: EORTC; Non-Financial Interests, Member, member of NSGO and NSGO-CTU Scientific Committee Member: NSGO - Nordic Society of Gynecological oncology; Non-Financial Interests, Member: The society of Lithuanian medical oncologists; Non-Financial Interests, Member of ESMO and POWG of ESMO: ESMO; Other, Assoc. Prof position: Vilnius University of Lithuania Faculty of Medicine. L. Greillier: Financial Interests, Personal, Advisory Board: AbbVie, AstraZeneca, BMS, MSD, Novartis, Sanofi, Takeda, Roche; Financial Interests, Personal, Invited Speaker: Lilly, Pfizer; Financial Interests, Institutional, Local PI: AstraZeneca, AbbVie, BMS, MSD, Novartis, Takeda, Pfizer, PharmaMar; Financial Interests, Institutional, Coordinating PI: Sanofi; Financial Interests, Personal, Local PI: Roche. H.J. Klumpen: Financial Interests, Institutional, Invited Speaker, Current Treatments of Cholangiocarcinoma: Medtalk; Financial Interests, Institutional, Invited Speaker, PODCAST on treatment of HCC: CCO; Financial Interests, Institutional, Advisory Board: Janssen, AstraZeneca; Financial Interests, Institutional, Local PI, IMBRAVE 050: ROCHE; Financial Interests, Institutional, Local PI, FIGHT 302: INCYTE; Financial Interests, Institutional, Local PI, LEAP 012: MSD; Financial Interests, Institutional, Local PI, TAS120: Taiho; Financial Interests, Institutional, Local PI, COMPETE, COMPOSE: ITM Solucin GmbH; Financial Interests, Institutional, Local PI, KEYNOTE 966: MSD; Financial Interests, Institutional, Local PI, COSMIC 312: Exelixis; Other, Subdomain leader G5.1: EURACAN; Other, In the Netherlands: Member National Guideline Committee For Biliary Tract Cancer; Other, in the Netherlands: Member of the National guideline committee for HCC. L.F.L. Licitra: Financial Interests, Personal, Advisory Board, for Expert Opinion in Advisory Boards: AstraZeneca, Bayer, BMS, Eisai, MSD, Merck–Serono, Boehringer Ingelheim, Hoffmann-La Roche Ltd, Novartis, Roche, Debiopharm International SA, Sobi, Incyte Biosciences Italy srl, Doxa Pharma srl, Amgen, Nanobiotics and 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, Buran. 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; Non-Financial Interests, Officer, International Thymic Malignancy Interest Group, President: ITMIG; 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. de Herder: Financial Interests, Personal, Advisory Board: Novartis, Ipsen; Financial Interests, Personal, Invited Speaker: Novartis, Ipsen; Non-Financial Interests, Leadership Role, Chairman EURACAN Domain 4 Rare Cancer of the Neuroendocrine System: EU. E. Kapiteijn: Financial Interests, Institutional, Advisory Board: BMS, Novartis, Pierre Fabre, Merck, Delcath, Bayer, Lilly; Financial Interests, Institutional, Coordinating PI: BMS, Pierre-Fabre, Delcath. A. Idbaih: Financial Interests, Personal, Advisory Board, Advisory board: Novocure, Leo Pharma, Boehringer Ingelheim, Novartis; Financial Interests, Institutional, Local PI, Clinical research: Enterome, Bristol Myers Squibb; Financial Interests, Institutional, Coordinating PI, Clinical research: Carthera; Financial Interests, Institutional, Local PI, Basic/Translational research: Carthera; Financial Interests, Institutional, Local PI, Basic and Translational research: Sanofi, Nutrithéragène, Servier, Transgene; Other, Travel Funding: Carthera, Leo Pharma, Novocure, Enterome. I.L. Ray-Coquard: Financial Interests, Personal, Advisory Board: Roche, GSK, AstraZeneca, Mersana, Deciphera, Amgen, Oxnea, Merck Sereno, Agenus, Novartis, Macrogenics, Clovis, EQRX, Adaptimmune, Eisai, SUTRO, BMS, Adaptimmune, Daiichi Sankyo; 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, Personal, Advisory Board: Bayer, Deciphera, GSK, Roche; Financial Interests, Personal, Invited Speaker: PharmaMar; Financial Interests, Institutional, Invited Speaker: MSD, MSD; Financial Interests, Personal, Other, Member of The Supervisory Board: Innate Pharma; 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.