All times are listed in CET (Central European Time).
- Jean-Yves Blay (Lyon, France)
- Claudia María Valverde Morales (Barcelona, Spain)
55O - IMADGIST: A randomized study of 6 vs 3 years of adjuvant imatinib in patients with localized GIST at high risk of relapse
- Axel Le Cesne (Villejuif, France)
Abstract
Background
Adjuvant imatinib is indicated after complete resection of primary, localized, KIT-positive GIST at high risk of recurrence. A large proportion of these patient relapse after the end of adjuvant imatinib. Whether prolonging adjuvant imatinib beyond 3 years may enable to reduce the risk of GIST recurrence has not been explored in a randomized setting.
Methods
IMADGIST (NCT02260505) is a multicenter open-label, randomized, phase III study evaluating maintenance of imatinib at the last dose routinely taken by the patient in the 3-year period prior to randomization (either 300 or 400 mg/d) compared to Interruption of imatinib treatment (STOP arm) from the day of randomization. Primary endpoint is Disease-Free Survival (DFS). Secondary endpoints include Overall Survival, (OS) Time to Imatinib Resistance, Rate of Complete Response after reintroduction, Safety and Quality of Life. A sample size of 134 patients was calculated to detect an improvement of 15% in 3-year DFS rate (75% vs. 90% in the
Results
From December 24th, 2014 to April 4th, 2023; 136 patients aged ≥ 18, ECOG PS ≤2, with confirmed diagnosis of localized GIST with documented KIT (CD117) positivity, complete surgical R0 or R1, and a risk of tumor recurrence ≥35% according to National Comprehensive Cancer Network Task Force on GIST (NCCN) risk classification were randomised by 14 French anticancer centers. Sixty five patients were randomized to the 3-year arm vs 71 in the 6 year arm. 63 and 73 patients with moderate ([35-70%]) or high (>70%) NCCN risk, respectively, were included. The final analysis is scheduled for Janaury 31st, 2024. THe results will be presented at the congress.
Conclusions
Data cut of was set to September 30th, 2023. Statistical analysis is in progress and results will be presented at the time of the congress.
Clinical trial identification
IMADGIST (NCT02260505).
Editorial acknowledgement
none
Legal entity responsible for the study
Centre Léon Bérard.
Funding
Programme Hospitalier de Recherche Clinique & Institut National du Cancer (INCA) & EURACAN.
Disclosure
A. Le Cesne, O. Bouche, M. Toulmonde, E. Bompas, F. Bertucci, L. Chaigneau, B. Landi, M. Pracht, S. Metzger, D. Perol: Financial Interests, Institutional, Research Grant: Novartis. O. Bouche: Financial Interests, Institutional, Research Grant: Novartis. N. Penel: Financial Interests, Institutional, Research Grant, Research grant for clinical trials in sarcoma filed: BAYER HealthCare. M. Brahmi: Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Invited Speaker: Amgen, PharmaMar, Deciphera. W. Lahlou: Financial Interests, Personal, Research Grant: Novartis. 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, Personal, Principal Investigator: PAOLA1; Non-Financial Interests, Personal, Other, President: GINECO. J-Y. 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.
56O - A phase Ia/Ib study of the MDM2-p53 antagonist brigimadlin (BI 907828): Safety and efficacy in patients with dedifferentiated liposarcoma
- Peter Reichardt (Berlin, Germany)
Abstract
Background
Targeting the MDM2–p53 interaction represents a potential therapeutic option in liposarcoma. In an earlier analysis of this phase Ia/Ib study (NCT03449381), brigimadlin, a highly potent, orally available MDM2–p53 antagonist showed promising safety and efficacy in patients (pts) with advanced solid tumours including DDLPS. Here we focus on safety and efficacy in pts with DDLPS.
Methods
In the phase Ia dose escalation, the recommended dose for expansion was defined as 45 mg on Day 1 of 21-day cycles (q3w; LoRusso et al.,
Results
As of 7 November 2023, 190 pts have been enrolled across phase Ia/Ib to receive brigimadlin q3w (52.6% male; 80.0% white; 55.8%/43.7% ECOG PS 0/1; median 2 prior lines of therapy). In 90 pts with DDLPS who received brigimadlin q3w, median PFS was 8.1 months. In 86 response-evaluable pts, one complete response and 15 partial responses were observed (ORR: 18.6%), and a best response of stable disease was observed in 60 pts (disease control rate: 88.4%). In pts with DDLPS treated in phase Ib (n=84), any-grade TRAEs were reported in 78 (92.9%) pts, most commonly nausea (n=63, 75.0%), fatigue (n=52, 61.9%) and neutropenia (n=45, 53.6%). Grade ≥3 TRAEs were reported in 36 (42.9%) pts, most commonly thrombocytopenia (n=19, 22.6%), neutropenia (n=19, 22.6%) and anaemia (n=8, 9.5%). Adverse events leading to treatment discontinuation occurred in 4 (4.8%) pts. An analysis of radiomic features of tumours will be presented.
Conclusions
Brigimadlin q3w demonstrated manageable toxicity and encouraging efficacy with a high rate of disease control in DDLPS pts. Brigimadlin is being evaluated versus doxorubicin as first-line treatment for pts with advanced DDLPS in the phase II/III Brightline-1 study (NCT05218499), for which the FDA has granted a Fast Track Designation.
Clinical trial identification
NCT03449381.
Editorial acknowledgement
Medical writing support for the development of this abstract under the direction of the authors was provided by Jim Sinclair, PhD, of Ashfield MedComms, an Inizio company, and was funded by Boehringer Ingelheim.
Legal entity responsible for the study
Boehringer Ingelheim.
Funding
Boehringer Ingelheim.
Disclosure
P. Schöffski: Financial Interests, Personal, Advisory Role: Deciphera, Ellipses Pharma, Transgene, Exelixis, Boehringer Ingelheim, Studiecentrum voor Kernenergie (SCK CEN), SQZ Biotechnology, Adcendo, PharmaMar, Merck, Medpace, Cogent Biosciences, Eisai, Curio Science, LLX Solutions, Servier, Biolumina, Genmab, Sanofi, Regeneron, Moleculin Biotech, Avacta Life Sciences, Amryt Pharma, UCB, Boxer Capital; Financial Interests, Institutional, Funding: CoBioRes NV, Eisai, G1 Therapeutics, PharmaMar, Genmab, Merck, Sartar Therapeutics, ONA therapeutics, Adcendo. P. Lorusso: Financial Interests, Personal, Advisory Board: AbbVie, Roche-Genentech, Takeda, Agenus, IQVIA, Pfizer, GSK, QED Therapeutics, AstraZeneca, AstraZeneca, EMD Serono, Kyowa Kirin Pharmaceutical Development, Kineta, Inc., Zentalis Pharmaceuticals, Molecular Templates, ABL Bio, STCube Pharmaceuticals, I-Mab, Seagen, imCheck, Relay Therapeutics, Stemline, Compass BADX, Mekanistic, Mersana Therapeutics, BAKX Therapeutics, Scenic Biotech, Qualigen, Roivant Sciences, NeuroTrials, Actuate Therapeutics, Atreca Development, Cullinan, Quanta Therapeutics, Schrodinger; Financial Interests, Personal, Other: SOTIO, Amgen CodeBreak 202, DrenBio, Boehringer Ingelheim. N. Yamamoto: Financial Interests, Personal, Other: Chugai Pharma, ONO Pharmaceuticals, Daiichi Sankyo/UCB Japan, Eisai; Financial Interests, Personal, Advisory Role: Eisai, Takeda, Boehringer Ingelheim, Cimic, Healios, Merck; Financial Interests, Institutional, Funding: Chiome Bioscience, Otsuka, Chugai Pharmaceuticals, Taiho Pharmaceuticals, Eisai, Astellas Pharma, Novartis, Daiichi Sankyo, Lilly Japan, Boehringer Ingelheim, Takeda, Kyowa Hakko Kirinn, Bayer, Pfizer, ONO Pharmaceutical, Janssen, MSD, AbbVie, Bristol Myers Squibb, Merck Serono, GSK, Sumitomo Dainippon, Carna Biosciences, Genmab/Seattle Genetics, Shionogi, Kaken Pharmaceutical, AstraZeneca, CMIC, Rakuten Medical. P. Reichardt: Financial Interests, Personal, Full or part-time Employment: Helios Klinikum Berlin-Buch GmbH; Financial Interests, Personal, Advisory Role: Bayer, Novartis, Roche, Deciphera, Mundibiopharma, PharmaMar, Blueprint Medicines, GSK, Boehringer Ingelheim; Financial Interests, Personal, Other: Clinigen, Deciphera, PharmaMar, Boehringer Ingelheim; Non-Financial Interests, Personal, Other: Chairman of the German Sarcoma Foundation. L. Schwartz: Financial Interests, Personal, Advisory Role: DSMB Member Regeneron, BMS, Merck. C. Hu, H.T. Landsteiner, G. Jayadeva: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. M. Gounder: Financial Interests, Personal, Other: Flatiron Health, PER, Medscape, Guidepoint Global, touchIME, Med Learning Group, More Health, More Health, Great Debates and Updates, GLG, OncLive/MJH Life Sciences, Epizyme, Desmoid Tumor Research Foundation; Financial Interests, Personal, Advisory Role: Daiichi Sankyo, Karyopharm Therapeutics, Epizyme, Bayer, Springworks Therapeutics, TYME, Boehringer Ingelheim, Ayala Pharmaceuticals, Rain Therapeutics, Regeneron; Financial Interests, Personal, Speaker’s Bureau: Amgen, Karyopharm Therapeutics, Boehringer Ingelheim; Financial Interests, Personal, Royalties: UpToDate; Financial Interests, Institutional, Royalties: GODDESS PRO Desmoid Tumor; Non-Financial Interests, Personal, Other: Foundation Medicine, Athenex. All other authors have declared no conflicts of interest.
Invited Discussant abstracts 55O and 56O
- Cesar Serrano (Barcelona, Spain)
Q&A and discussion
40O - Diagnostic trajectories of rare cancer patients in the Netherlands: Results from a nationwide cross-sectional survey
- Olga Husson (Amsterdam, Netherlands)
Abstract
Background
Diagnosing rare cancers is challenging, often involving prolonged diagnostic trajectories. This study examined the diagnostic journey of rare cancer patients and explored differences between subgroups (solid vs. non-solid tumours and 10 EURACAN domains).
Methods
Recruited via patient advocacy groups, 1,540 patients answered a nationwide online survey about their diagnostic journey, including time between first general practitioner (GP) consultation to hospital referral, initial diagnosis accuracy, and number of hospital visits before final diagnosis. Diagnostic journeys were compared between rare cancer subgroups.
Results
Diagnostic timelines varied from <3 up to >12 months, with most patients consulting GPs (76%) and being referred to a hospital within >3 months (76.3%). Extended GP-to-hospital waits mainly impacted neuroendocrine tumour (NET; 21.7%), endocrine tumour (17.5%) and haematological patients (13.4%). Once at the hospital, 14.5% of patients waited >3 months for a final diagnosis. Almost a third of patients (32.1%) reported receiving an incorrect diagnosis, and 44.6% of them underwent treatment or took medication for the (perceived) incorrect diagnosis. Correct initial diagnosis varied significantly between solid and non-solid groups (p<0.001). Non-solid cancer patients often received a correct diagnosis in a single hospital visit (75%), while solid cancer patients needed 2 or more visits (57.7%). Sarcoma patients most often reported having received >1 incorrect initial diagnoses (19.5%). Rare skin cancer and non-cutaneous melanoma, head and neck, and thoracic cancer patients often visited multiple hospitals before receiving an accurate diagnosis (56.7%, 53.8% and 50.0%).
Conclusions
Delays in diagnosis and diagnostic accuracy pose serious challenges for patients with rare cancers. Risk groups for longer journeys include NET or endocrine tumours patients, while sarcoma patients face higher incorrect initial diagnoses. Diverse diagnostic journeys emphasize the need for regional clinical networks for rare cancers to quicken and ensure a correct diagnosis.
Legal entity responsible for the study
The Netherlands Cancer Institute.
Funding
European Organization for Research and Treatment of Cancer - Quality of Life Group (EORTC QLG).
Disclosure
All authors have declared no conflicts of interest.
146O - Measuring health-related quality of life in solid rare cancer patients according to EURACAN domains: A progress report of an EORTC Quality of Life group (QLG) study
- Catarina S. Simoes Padilla (Amsterdam, Netherlands)
Abstract
Background
Patients with a rare cancer report lower health-related quality of life (HRQoL) than common cancer patients. Specific HRQoL measures are required to better assess the unique physical and psychosocial issues faced by rare cancer patients. This EORTC Quality of Life Group (QLG) study investigates how HRQoL is currently measured in clinical research among these patients, identifies HRQoL issues patients face due to the disease’s rarity, and evaluates the content validity of EORTC HRQoL questionnaires. Initiated in 2023, here we present an update of the study.
Methods
A mixed-method study is used by two systematic literature reviews (one on HRQoL measures currently used and one on healthcare experiences) and a global, multicentre study collecting qualitative (interviews) and quantitative (questionnaires) data on HRQoL of rare cancer patients with a solid tumour. The EURACAN domain division is used to analyse HRQoL differences in subgroup of patients. Data from patients and healthcare professionals assess content validity, importance and relevance of items in existing EORTC questionnaires (tumour-specific modules and stand-alone healthcare-related questionnaires).
Results
The first review yielded 18,704 articles, with 1416 screened, and 608 data-extracted. Early results reveal the EORTC C30 questionnaire as the most common used HRQoL measurement. Over half of the studies utilize general and tumour-specific instruments. The second review on healthcare system issues has yet to start. Qualitative and quantitative analysis are ongoing. Out of the planned 500 patient interviews and questionnaires, 184 have been completed, enabling analysis in 11 of the 20 EURACAN (sub)domains. Out of 150 planned interviews and questionnaires with healthcare professionals, 114 have been gathered.
Conclusions
Preliminary results confirm the lack of specific HRQoL measures for rare cancer patients. The results of the second part of this project will help the development of a guidance document to advise on how to best measure HRQoL in solid rare cancers. Given the large diversity, a flexible strategy is expected (e.g., construction of item lists with validated items from the EORTC QLG Item Library).
Legal entity responsible for the study
EORTC QLG.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
51O - The European Prospective Investigation into Cancer and nutrition cohort (EPIC): A gateway to rare cancer epidemiological research – Insights from the EPIC Rare Cancers Working Group
- Matthieu Foll (Lyon, France)
Abstract
Background
Despite its pivotal role in cancer epidemiology, the EPIC study's potential for rare cancer research has been underutilized, primarily due to the complexity of curating comprehensive data. The collaboration with the RARECAREnet project has enabled the utilization of EPIC's data for rare cancer investigations.
Methods
The EPIC study's cohort of over 500,000 participants, recruited across Europe, provided a rich data set of lifestyle, diet, and health information. Rare cancers were identified according to the RARECAREnet classification, which includes incidence-based categorization and detailed morphological and site-specific information. To maximize the utility of this data, an R shiny web application was developed, aimed at enabling data exploration.
Results
Among the EPIC participants, 8,851 rare cancer cases were identified, encompassing a wide range of cancer sites and morphologies. The basic descriptive epidemiology of these cases aligns with previously reported statistics, such as sex ratio and incidence rates. Crucially, the R shiny web application offers the ability to explore this database interactively. This tool is designed for preliminary data analysis and hypothesis testing, aiding researchers in assessing the feasibility and potential of initiating detailed epidemiological studies on specific rare cancers.
Conclusions
The EPIC rare cancers database, enhanced by the development of an interactive web application, represents a significant step forward in rare cancer research. It's vital to promote awareness of this resource within the research community, especially in light of the anticipated 2024 participant follow-up update, expected to yield critical sample sizes necessary for rare cancer studies and making it an essential tool for advancing research in this field.
Legal entity responsible for the study
The authors.
Funding
International Agency for Research on Cancer.
Disclosure
All authors have declared no conflicts of interest.
Invited Discussant abstracts 40O, 146O and 51O
- Joanna Szkandera (Graz, Austria)