Abstract 49P
Background
Early-onset cancer (EOC) exhibits unique biological and clinical features. Most cases are sporadic cancers, with environmental factors (e.g. diet, pollution) driving metabolic inflammation, which promotes cell proliferation and immune suppression. This study aims to assess clinical outcomes in EOC patients (pts) enrolled in early clinical trials (ECT) with PD-1/PD-L1 immune checkpoint inhibitors (ICIs), with the goal of identifying patterns to inform future trial designs.
Methods
A retrospective study of pts treated with ICIs at VHIO's Phase I unit (2018–2023) using the 'Inmunomics' database. We compared EOC (18-49 years) to late-onset cancer (LOC, 50+ years). Demographic and treatment data were analyzed using Chi-squared/Fisher’s tests for categorical and Wilcoxon rank-sum test for continuous variables. Kaplan-Meier curves were fitted for progression-free survival (PFS) on ECT with ICIs, and overall survival (OS) from start of ECT with ICIs.
Results
Of 428 pts treated with ICIs, 114 (30%) were classified as EOC. No differences in ECOG, presence of liver metastases (mets), or prevalence of “hot” tumor type (ICI single agent approved) were observed between EOC and LOC (p>0.05). EOC pts had more prior treatment lines (3 vs. 2, p=0.03), while LOC pts had more comorbidities and stage IV at diagnosis (p=0.014). Tumor types in EOC included breast (23%) and melanoma (21%), while LOC included microsatellite stable colorectal (25%), and gastrointestinal non-CRC (18%). In univariate analysis, derived neutrophil-to-lymphocyte ratio (dNLR), LDH, albumin, liver mets, and sum of target lesions (TL) were significant predictors of OS (p<0.05). Multivariate analysis confirmed low LDH, high albumin, and smaller sum of TL as independent factors for better OS (p<0.05). After propensity score matching for gender, tumor types, prior ICI treatments, and previous lines of treatment, no differences in median OS (9.8 versus 10.7, HR=1; 95%CI 0.7-1.4) or median PFS (1.9 versus 2.1, HR=0.8; 95%CI 0.6-1.1) were found between EOC and LOC, respectively.
Conclusions
One-third of pts treated in ECT with PD1/L1 inhibitors have EOC, with PFS and OS comparable to LOC. Outcomes are strongly determined by laboratory parameters (LDH, albumin), and tumor burden at study entry.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
VHIO.
Funding
La Caixa, BBVA, AECC.
Disclosure
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; Other, Personal, Other, Travel expenses: Recordati. A. Hernando Calvo: Financial Interests, Personal, Expert Testimony: Merus; Financial Interests, Institutional, Research Grant: Gilead; Other, Personal, Other, Travel support: Merck Serono, Kyowa Kirin, Bristol Myers Squibb. M.J. Lostes Bardaji: Non-Financial Interests, Personal, Affiliate: SEOM, ESMO. 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 Ingellheim; 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. R.D.A. Toledo: Financial Interests, Institutional, Research Grant, Research Funding: Novartis, AstraZeneca, Beigene Pharmaceuticals. M. Vieito: Financial Interests, Personal, Invited Speaker: Novocure; Financial Interests, Personal, Other, Steering committee member: BMS; Non-Financial Interests, Personal, Principal Investigator: Roche, BMS, Taiho, Hutchinson Pharma, Novartis, Mundipharma, Enterome, Debiopharm. R. Dienstmann: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Boehringer Ingelheim, Ipsen, Libbs, Lilly, Merck Sharp & Dohme, Roche, Sanofi, Servier, GSK, Takeda, Janssen, Gilead, Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Roche, Foundation Medicine; 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; Financial Interests, Institutional, Research Grant: Novartis, AstraZeneca, Daiichi-Sankyo, GSK. E. Garralda: Financial Interests, Personal, Advisory Board: Roche, Ellipses Pharma, Boehringer Ingelheim, Janssen Global Services, Seattle Genetics, Anaveon, Hengrui, Sanofi, Incyte, Medscape, Skypta, Sotio, AbbVie, Astex Therapeutics, Alentis Therapeutics, Marengo Therapeutics, Medpace, Pfizer, Amgen, GenMab, GreyWolf, Gilead, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: MSD, Roche, Novartis, SeaGen, PPD, Aran, The Ricky Rubio Fundation, ESMO, Fundación SEOM, CDDF, Springer Nature, Karger, Doctaforum, Tactics, AEFI, Fundación ECO, ESO (European School of Oncology), MeetingPharma, AstraZeneca, Alcura, Horizon CME; Financial Interests, Personal, Full or part-time Employment: NEXT Oncology; Financial Interests, Personal, Stocks/Shares: 1TRIALSP; Financial Interests, Institutional, Research Grant: Novartis, Roche, Thermo Fisher, AstraZeneca, Taiho, Beigene, Janssen, Anaveon. All other authors have declared no conflicts of interest.