1. Determinants of activity and efficacy of anti-PD1/PD-L1 therapy in patients with advanced solid tumors recruited in a clinical trials unit: a longitudinal prospective biomarker-based study
- Author
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Javier García-Corbacho, Alberto Indacochea, Azucena E. González Navarro, Iván Victoria, Débora Moreno, David Pesántez, Laura Angelats, Andrea Modrego-Sanchez, Esther Sanfeliu, Oleguer Castillo, Paula Blasco, Laura Mezquita, Nuria Viñolas, Miquel Nogué, Patricia Galván, Barbara Adamo, Neus Basté, Tamara Sauri, Manel Juan, Aleix Prat, Francesco Schettini, [García-Corbacho J] Medical Oncology Department, Hospital Clinic of Barcelona, Barcelona, Spain. Medical Oncology Department (UGCI), Virgen de La Victoria and Regional University Hospital / IBIMA, Málaga, Spain. [Indacochea A] Medical Oncology Department, Hospital Clinic of Barcelona, Barcelona, Spain. Medical Oncology Department, Hospital General de Granollers, Granollers, Spain. [González Navarro AE] Immunology Department, Hospital Clinic of Barcelona, Barcelona, Spain. [Victoria I, Moreno D, Pesántez D] Medical Oncology Department, Hospital Clinic of Barcelona, Barcelona, Spain. [Nogué M] Medical Oncology Department, Hospital General de Granollers, Granollers, Spain, and Hospital General de Granollers
- Subjects
aminoácidos, péptidos y proteínas::proteínas::proteínas de membranas::receptores de superficie celular::receptores inmunológicos::receptores inhibidores y coestimuladores de células T::receptor 1 de la muerte celular programada [COMPUESTOS QUÍMICOS Y DROGAS] ,Cancer Research ,Oncology ,Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Costimulatory and Inhibitory T-Cell Receptors::Programmed Cell Death 1 Receptor [CHEMICALS AND DRUGS] ,Marcadors bioquímics ,terapéutica::terapia biológica::inmunomodulación::inmunoterapia [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Immunology ,Immunoteràpia ,Immunology and Allergy ,Biological Factors::Biomarkers [CHEMICALS AND DRUGS] ,factores biológicos::biomarcadores [COMPUESTOS QUÍMICOS Y DROGAS] ,Tumors - Abstract
Immune-checkpoint inhibitors (ICI) have revolutionized the therapeutic landscape of cancer. However, optimal patient selection is still an unmet need. One-hundred-forty-six patients with metastatic cancer candidates to ICI at the Hospital Clinic of Barcelona Clinical Trials Unit were prospectively recruited in this observational study. Blood samples were collected at different timepoints, baseline LIPI score calculated and pre-ICI archived tissues retrieved to evaluate PD-L1, tumor-infiltrating lymphocytes (TILs) and PD1 mRNA levels. Tumor assessments were centrally reviewed by RECIST 1.1 criteria. Associations with overall response rates (ORR), durable clinical benefit (DCB), progression-free survival (PFS) and overall survival (OS) were performed with univariable/multivariable logistic and Cox regressions, where appropriate. At a median follow-up of 26.9 months, median PFS and OS were 2.7 and 12.9 months. Response rates were 17.8% with duration of response (DOR) of 4.4 months. LIPI score was independently associated with PFS (p = 0.025) and OS (p p = 0.005). Time-to-best response (TTBR) and ORR (p p p = 0.028) and DCB (univariate p = 0.043). PD1 mRNA levels were strikingly associated to complete responses (p = 0.021). To resume, in our prospective observational pan-cancer study, baseline LIPI score, immunotherapy-naïve status, cancer type and RT before starting ICI were the most relevant clinical factors independently correlated with immunotherapy outcomes. Longer TTBR seemed to associate with better survival, while PD1 mRNA and PD-L1 protein levels might be tumor-agnostic predictive factors of response to ICI and should be furtherly explored.
- Published
- 2023
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