538P - Single-center retrospective analysis of patients with brain metastases included in early phase clinical trials

Background

Historically patients (pts) with brain metastases (BM) were excluded from early phase clinical trials due to concerns over prognosis, risk of toxicity or lack of brain penetrance. Recent trials allow the inclusion of pts with stable (asymptomatic and/or treated) BM, as recommended by the ASCO and Friends of Cancer Research Brain Metastases Working Group. We aimed to describe the outcomes of patients with BM enrolled in early phase clinical trials.

Methods

Retrospective cohort analysis of clinical and treatment (trt) response data of pts included in early phase clinical trials at Vall d'Hebron Institute of Oncology between January 2012 and April 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 815 pts treated at our center were analyzed; 51 pts had stable BM at inclusion, 28 (54.9%) male and 23 (45.1%) female. Most frequent types: lung (51.0%), melanoma/skin (23.5%). Forty-one pts (80.4%) received prior brain trt: 37 radiotherapy, 3 surgery and 1 both. Ten pts (19.6%) were included with asymptomatic untreated BM. Type of experimental trt: immunotherapy 72.5%, targeted therapy 21.6%, antibody-drug conjugates 5.9%. Phase of clinical trial in which pts were included: phase 1 dose escalation 23.5%, phase 1 expansion cohorts 70.6%, and phase 2 basket studies 5.6%. Median OS in pts without BM was comparable to those with: 9.1 months vs 6.3 (p=not significant); median PFS was superior in BM pts: 1.8 vs 2.6 (HR 0.52, p<0.0001). The rate of OS<3 months was 31.4% in BM pts and 33.3% had PFS>4 months. ORR and DCR were respectively 19.6% and 54.9%, intracranial ORR and DCR were 7.8% and 72.7%. Only 4 pts discontinued treatment due to isolated intracranial progression (iPD), and 2 had iPD as best response. There were no statistically significant differences in PFS and OS of pts with treated BM and asymptomatic untreated BM.

Conclusions

The trt response and survival data for pts with BM in our cohort support the recommendations of ASCO and Friends of Cancer Research on the inclusion of pts with BM in clinical trials.

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, Travel support: Merck Serono, Kyowa Kirin. C. Saura Manich: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Bristol Meyers Squibb, 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 Pharma, Sanofi-Aventis, SeaGen, Zymeworks, Genentech, Innoup, Millenium, Pharmalex Spain SLU; Financial Interests, Personal, Other, SC: Byondis B.V., GSK, Macrogenics, Menarini, Merus, Synthon Biopharpaceuticals; Financial Interests, Institutional, Research Grant: AstraZeneca, Bayer Pharma, Boehringer Ingelheim, Bristol Myers Squibb (Bristol Myers Squibb), 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, Coordinating PI: Byondis B.V.; Non-Financial Interests, 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, 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; Financial Interests, Personal, Invited Speaker: Organon, Novartis; 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, Other, Coordinator of the SEOM +MIR Section of Residents and Young Assistants: Sociedad Española de Oncología Médica (SEOM); Non-Financial Interests, Other, Speaker of the ESMO Academy: European Society for Medical Oncology (ESMO); Non-Financial Interests, Other, Volunteer member of the ASCO Annual Meeting Scientific Program Committee: Developmental Therapeutics – Immunotherapy: American Society of Clinical Oncology (ASCO); Other, Travel, accommodations, expenses: Roche, Merck Serono, Sanofi, Amgen, Array BioPharma, Servier, Bristol Myers Squibb. I. Braña: Financial Interests, Personal, Advisory Board: Achilles Therapeutics, Bristol Myers Squibb, Cancer Expert Now, eTheRNA Immunotherapies, Merck Serono, Merck Sharp & Dohme (MSD), Rakuten Pharma, Boehringer Ingellheim, PCI Biotech, Guidepoint; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Merck Serono, Merck Sharp & Dohme (MSD), Roche; Financial Interests, Institutional, Local PI: 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, Principal Investigator, Basket of baskets: Cancer Core Europe; Non-Financial Interests, Member, Head and Neck Group: EORTC; Non-Financial Interests, Member: SEOM, ASCO. A. Callejo Perez: Financial Interests, Personal, Advisory Board: Boheringer Ingelheim, Pfizer, Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Other, Travel accomodation: MSD; Financial Interests, Personal, Other, Travel acommodation: Takeda. 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, Local PI, 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, , Leadership Role, President (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Member, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform); Non-Financial Interests, Member, Member of the Scientiffic Advisory Committee: CAC Hospital Universitari Parc Taulí. E. Garralda: Financial Interests, Personal, Advisory Board: Roche, Ellipses Pharma, Boehringer Ingelheim, Janssen Global Services, Seattle Genetics, Alkermes, Thermo Fisher, MabDiscovery, Anaveon, Hengrui, F-Star Therapeutics, Sanofi, Incyte; Financial Interests, Personal, Invited Speaker: MSD, Lilly, Roche, Thermo Fisher, Novartis, SeaGen; Financial Interests, Personal, Full or part-time Employment: NEXT Oncology; Financial Interests, Institutional, Funding: Novartis, Roche, Thermo Fisher, AstraZeneca, Taiho; Financial Interests, Institutional, Research Grant: BeiGene, Janssen. M. Vieito Villar: Non-Financial Interests, Principal Investigator: Roche, Bristol Myers Squibb, Taiho, Hutchinson Pharma, Novartis, Mundipharma, Enterome, Debiopharm. All other authors have declared no conflicts of interest.