Abstract 99P
Background
Phase 1 trials permit the inclusion of patients (pts) with asymptomatic and/or treated brain metastasis (BM). Yet, patient selection is challenging. Understanding correlations between molecular alterations and treatment efficacy is crucial. We aimed to analyze treament responses and molecular correlations in BM pts enrolled in early phase trials.
Methods
Retrospective cohort analysis of clinical, molecular and treatment response data of pts included in early phase clinical trials at Vall d'Hebron Institute of Oncology between January 2012 and July 2023. Objective response rate (ORR) and disease control rate (DCR) were calculated. Median progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method, survival between groups was compared using log-rank test and Cox regression.
Results
A total of 825 pts treated at our center were analyzed; 59 pts had asymptomatic and/or treated BM at inclusion, 28 (47.5%) male and 31 (52.5%) female. The most frequent tumor type was lung (49.2%), cutaneous (23.7%), head and neck (13.6%). Forty-nine pts (83.0%) received prior brain treatment (RT 78%, surgery 7.8%). A total of 33 pts (55.9%) underwent NGS analysis, 5 on blood (8.5%) and 28 on tissue (47.5%); 14 pts (23.7%) were included in genomically matched available clinical trials (GMt). The OS in pts without BM was comparable to those with: 9.1 months (m) vs 7.6 m (HR 0.91, p=0.57); median PFS was superior in BM pts: 1.8 vs 3.2 m (HR 0.53, p<0.0001). In BM pts the rate of OS<3 m was 22.0% and 45.8% had PFS>4 m. Only 5 pts out of 59 discontinued treatment due to isolated intracranial progression (iPD), and only 2 had iPD as best response. A trend towards better PFS and OS was observed for pts enrolled in GMt as compared to non-matched, PFS 5.5 vs 2.1 m (HR 0.71, p=0.324) and OS 26.48 vs 6.38 m (HR 0.56, p=0.171). In pts included in GMt ORR and DCR were statistically better than non-matched. ORR in GMt was 57.1% vs 25.4% in non-matched, and intracranial ORR was 42.6% vs 11.9%. DCR in GMt was 71.4% vs 59.3% in non-matched, and intracranial DCR was 85.7% vs 67.8%.
Conclusions
Our series supports the inclusion of pts with stable BM in early clinical trials. Increased ORR and DCR in pts included GMt may supports the use of NGS to guide treatment in pts with BM.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
This research has been funded by the Comprehensive Program of Cancer Immunotherapy & Immunology II (CAIMI-II) supported by the BBVA Foundation (grant 53/2021). The research leading to these results has received funding from ”la Caixa” Foundation (LCF/PR/CE07/50610001). Cellex Foundation for providing research facilities and equipment.
Disclosure
A. Hernando Calvo: Other, Personal, Other, Travel support: Merck Serono, Kyowa Kirin. O. Mirallas: Financial Interests, Personal, Invited Speaker: ROVI; Financial Interests, Institutional, Invited Speaker: Roche, Merck; Other, Personal, Other, Travel Expenses: Kyowa Kirin, Almirall; Other, Personal, Other, Travel Expenses and Conference Fee: Sanofi. C. Saura Manich: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Eisai, Exact Sciences, Exeter Pharma, F. Hoffmann - La Roche Ltd., Gilead, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Philips, Piere Fabre, PintPharma, Puma, Roche Farma, Sanofi.-Aventis, Seagen, Zymeworks, Pharmalex Spain SLU; Financial Interests, Personal, Expert Testimony: Boehringer Ingelheim, Bristol Meyers Squibb, Genentech, Innoup, Millennium; Financial Interests, Personal, Other, SC: Byondis B.V., GSK, Macrogenics, Menarini, Merus, Synthon Biopharmaceuticals; Financial Interests, Institutional, Research Grant: AstraZeneca, Bayer Pharma, Boehringer Ingelheim, Bristol Myers Squibb (BMS), Cytomx Therapeutics, Daiichi Sankyo, Eli Lilly and Company, F. Hoffmann-La RocheLtd., Genentech, GSK, Immunomedics, Innoup Farma, Macrogenics, Menarini Ricerche, Merus, Novartis, Pfizer, Puma, Roche, Sanofi-Aventis, Seattle Genetics; Financial Interests, Institutional, Invited Speaker: Byondis B.V.; Non-Financial Interests, Personal, Member: Spanish Society of Medical Oncology (SEOM), American Society for Clinical Oncology (ASCO), Geicam (Spanish Breast Cancer Research Group), European Society for Medical Oncology (ESMO), Sinology Society of the Official College of Physicians of Barcelona (COMB); Non-Financial Interests, Personal, Member, Junta Directiva y Comité Científico: SOLTI group (Academic research group in breast cancer). M.E. Elez Fernandez: Financial Interests, Personal, Advisory Board: Hoffman La - Roche, Servier, Amgen, Merck Serono, Sanofi, Bayer, Pierre Fabre, MSD, Takeda; Financial Interests, Personal, Invited Speaker: Organon, Novartis, Pfizer; Financial Interests, Personal, Other, Educational training: Seagen International GmbH; Financial Interests, Institutional, Funding: Hoffmann-La Roche Ltd., Sanofi Aventis Recherche & Développement, Amgen Inc., Boehringer Ingelheim, Novartis Farmacéutica SA, Bristol Myers Squibb International Corporation, BeiGene, HalioDX SAS, Janssen-Cilag SA, Merck Health KGAA, Merck Sharp & Dohme de España SA, PharmaMar SA, Servier, Taiho Pharma USA Inc, Hutchison MediPharma International, Menarini, Merus NV, Pfizer, Mirati, Array Biopharma Inc, AstraZeneca Pharmaceuticals LP, Celgene International SARL, Debiopharm International SA, Genentech Inc, MedImmune; Non-Financial Interests, Personal, Other, Coordinator of the SEOM +MIR Section of Residents and Young Assistants: Sociedad Española de Oncología Médica (SEOM); Non-Financial Interests, Personal, Other, Speaker of the ESMO Academy: European Society for Medical Oncology (ESMO); Non-Financial Interests, Personal, Other, Volunteer member of the ASCO Annual Meeting Scientific Program Committee: Developmental Therapeutics – Immunotherapy: American Society of Clinical Oncology (ASCO); Other, Personal, Other, Travel, accommodations, expenses: Roche, Merck Serono, Sanofi, Amgen, Array BioPharma, Servier, Bristol Myers Squibb. E. Muñoz Couselo: Financial Interests, Personal, Advisory Board: BMS, Novartis, Sanofi, Pierre Fabre, Sun Pharma, MSD; Financial Interests, Personal, Invited Speaker: Novartis, Roche, BMS, Sanofi, MSD, Pierre Fabre. I. Braña: Financial Interests, Personal, Advisory Board: Achilles Therapeutics, Bristol Myers Squibb, eTheRNA Immunotherapies, Merck Sharp & Dohme (MSD), Rakuten Pharma, PCI Biotech, Guidepoint; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Merck Serono, Merck Sharp & Dohme (MSD), Roche; Financial Interests, Personal, Expert Testimony: Cancer Expert Now, Merck Serono, Boehringer Ingelheim; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, GSK, Gliknik, Incyte, ISA pharmaceuticals, Janssen Oncology, Kura, Merck Serono, Debiopharm, Merck Sharp & Dohme (MSD), Nanobiotix, Novartis, Northern Biologics, Regeneron, Pfizer, Seattle Genetics, Shattuck Labs, VCN Biosciences, Roche, Immutep, MacroGenics, Sanofi, PharmaMar, Odonate Therapeutics, Bicycle Therapeutics, Dragonfly therapeutics, Gilead; Non-Financial Interests, Personal, Principal Investigator, Basket of baskets: Cancer Core Europe; Non-Financial Interests, Personal, Member, Head and Neck Group: EORTC; Non-Financial Interests, Personal, Member: SEOM, ASCO. J.C. Galceran: Financial Interests, Personal, Advisory Board: Astellas Pharma, AstraZeneca, Bayer, Johnson & Johnson, MSD Oncology, Novartis (AAA), Roche, Sanofi; Financial Interests, Institutional, Invited Speaker: Janssen-Cilag International NV, Lilly, S.A, Medimmune, Novartis Farmacéutica, S.A, Sanofi-Aventis, S.A; Other, Personal, Other, Member of the Commission: Catalan Program of Ambulatory Medication Commission (CAHMDA). E. Felip: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Gilead, GSK, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Peptomyc, Regeneron, Sanofi, Takeda, Turning Point, Pfizer; Financial Interests, Personal, Invited Speaker: Amgen, Daiichi Sankyo, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, PeerVoice, Pfizer, Sanofi, Takeda, Touch Oncology, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Merck Sharp & Dohme; Financial Interests, Personal, Member of Board of Directors, Independent member: Grifols; Financial Interests, Institutional, Invited Speaker, Clinical Trial: AstraZeneca AB, AbbVie, Amgen, Bayer Consumer Care AG, Beigene, Boehringer Ingelheim GmbH, Bristol Myers Squibb International Corporation, Daiichi Sankyo Inc., Exelixis Inc., F. Hoffmann-La Roche Ltd., Genentech Inc., GSK Research and Development Limited, Janssen Cilag International NV, Merck Sharp & Dohme Corp, Merck KGAA, Mirati Therapeutics Inc, Novartis Pharmaceutica SA, Pfizer, Takeda Pharmaceuticals International; Non-Financial Interests, Personal, Leadership Role, President (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Personal, Member, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform); Non-Financial Interests, Personal, Member, Member of the Scientific Advisory Committee: CAC Hospital Universitari Parc Taulí. E. Garralda: Financial Interests, Personal, Invited Speaker: MSD, Roche, Thermo Fisher, Novartis, Seagen; Financial Interests, Personal, Advisory Board: Roche, Ellipses Pharma, Boehringer Ingelheim, Janssen Global Services, Seattle Genetics, Thermo Fisher, MabDiscovery, Anaveon, Hengrui, F-Star Therapeutics, Sanofi, Incyte, Medscape; Financial Interests, Personal, Full or part-time Employment: NEXT Oncology; Financial Interests, Personal, Stocks/Shares: 1TRIALSP; Financial Interests, Institutional, Funding: Novartis, Roche, Thermo Fisher, AstraZeneca, Taiho; Financial Interests, Institutional, Research Grant: Beigene, Janssen. M. Vieito Villar: Non-Financial Interests, Personal, Principal Investigator: Roche, BMS, Taiho, Hutchinson Pharma, Novartis, Mundipharma, Enterome, Debiopharm. All other authors have declared no conflicts of interest.