2314P - Quality and safety of research biopsies (RB) in oncology clinical trials

Background

The scientific benefits gained from studying RB in oncology clinical trials depends on sample quality and there are concerns that participant risk might outweigh the benefits.

Methods

RB data from patients who participated in oncology clinical trials at a single institution between January 2017 and December 2020 were analyzed for sample quality assessed by tumor content (TC) and safety. Determinants of high-quality RB and complications were investigated. Quality was compared with sample taken at external institutions and sent to our laboratory for centralized assessment in the context of multicentric breast cancer clinical trials.

Results

The cohort consisted of 6805 samples obtained from 3104 procedures performed in 1983 patients from 386 studies. The median number of samples collected per study was 5, with an average of 2.2 samples/procedure. Samples were collected mainly at screening (72%), from metastatic sites (63%), and using ultrasound-guided procedure (60%). Liver was the most biopsied organ (33%), followed by lymph nodes (13%) and breast (12%). Preservation methods were formalin-fixed and paraffin embedded (FFPE, 50.5%), snap frozen (21.5%) or alternatively stabilized (28%) according to study protocols. The median TC of the 2940 FFPE samples analyzed was 70% (95% CI, 70-70). 85% of samples had >10% TC and 60% had >50% TC. Any grade complications occurred in 15% of procedures, with pain being the most frequent (11%; 0.4% Grade 3-4). Major complications were observed in 0.9% of procedures. A higher number of complications were found for lung RB (34%; Grade 3-4, 2.6%). In multivariable logistic model, visceral site, guided procedure and number of samples collected were associated with higher TC. On treatment biopsy, non-guided procedure and visceral site were independently associated with a higher risk of major complications. In the comparative analysis with an international cohort of 2302 baseline breast cancer RB obtained from sites in 38 countries, major heterogeneity was observed across countries, with median TC ranging from 0% to 80%.

Conclusions

High quality RB have acceptable safety with low risk of major complications. Our comparative analysis suggests that while local collection of high-quality RB is feasible, quality could be improved at some centers.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Fundacion "La Caixa".

Disclosure

P.G. Nuciforo: Financial Interests, Personal, Advisory Role: Bayer, MSD Oncology; Financial Interests, Personal, Training: Targos. C. Saura Manich: Financial Interests, Personal, Advisory Role: AstraZeneca, Daiichi Sankyo, Eisai, MediTech, Novartis, Pfizer, Philips Healthcare, Pierre Fabre, Puma Biotechnology, Roche; Financial Interests, Institutional, Funding: Puma Biotechnology, Roche, Aragon Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Bayer, Bristol Myers Squibb, CytomX Therapeutics, Daiichi Sankyo, Genentech, German Breast Group, GSK, InnoUp, International Breast Cancer Study Group, Lilly, Macrogenics, Medica Scientia Innovation Research, Menarini, Millennium Pharmaceuticals, Novartis, Pfizer, Queen Mary, Sanofi/Aventis, SOLTI, Netherlands Cancer Institute. 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. 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Hoffmann-La Roche Ltd., Genentech Inc., HalioDX SAS, Hutchinson Medipharma, Janssen-Cilag International NV, Merus NV, Taiho Pharma USA Inc.; Non-Financial Interests, Other, Coordinating PI. Clinical Trials & Research: Mirati; Non-Financial Interests, Member: AACR, ASCO, EACR, EORTC, SEOM; Other, President: Oncology Master Plan – Catalonia Department of Health; Other, Advisory Committee: Advisory Committee on Pharmaceutical Provision Financing under the Spanish National Health System. E. Felip: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Eli Lilly, GSK, Janssen, Merck Sharp & Dohme, Pfizer, Sanofi, Takeda, Merck Serono, Peptomyc, F. Hoffmann-La Roche, Novartis, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol Myers Squibb, Eli Lilly, Medscape, Merck Sharp & Dohme, Peervoice, Pfizer, Amgen, F. Hoffmann-La Roche, Janssen, Medical Trends, Merck Serono, Sanofi, Takeda, TouchONCOLOGY; Financial Interests, Institutional, Other, Grant for Oncology Innovation: Merck Healthcare KGaA; Financial Interests, Institutional, Other, Fundación Merck SALUD: Fundación Merck SALUD; Financial Interests, Personal, Member of Board of Directors, Independent member: Grifols; Financial Interests, Institutional, Invited Speaker, Clinical Trial: F. Hoffmann-La Roche Ltd., Merck Sharp & Dohme Corp, AstraZeneca AB, Daiichi Sankyo Inc., Exelixis Inc., Merck KGAA, Janssen Cilag International NV, GSK Research & Development Limited, AbbVie Deutschland GmbH & Co KG, Novartis Pharmaceutica SA, Bayer Consumer Care AG, Takeda Pharmaceuticals International, Boehringer Ingelheim International GmbH, Pfizer S.L.U., Amgen Inc., Bristol Myers Squibb International Corporation (BMS), Mirati Therapeutics Inc.; Non-Financial Interests, Leadership Role, President (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Member, Member of ESMO Nominating Committee and Compliance Committee: ESMO; Non-Financial Interests, Member, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform). 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. R. Dienstmann: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Boehringer Ingelheim, Ipsen, Libbs, Lilly, Merck Sharp & Dohme, Roche, Sanofi, Servier, GSK, Takeda, Janssen, Foundation Medicine; Financial Interests, Personal, Advisory Board: Bayer, Roche; Financial Interests, Personal, Full or part-time Employment, Oncoclínicas is a private healthcare provider in Brazil. I work part time as Medical Director of the Precision Medicine and Big Data Initiative. We develop molecular tests (pathology and genomics) that are offered to patients treated in the organisation as part of support programs sponsored by pharmaceutical companies and I coordinate research activities with real-world clinico-genomics cohorts: Oncoclínicas; Financial Interests, Personal, Stocks/Shares: Trialing; Financial Interests, Personal, Research Grant: Merck. All other authors have declared no conflicts of interest.