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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

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 r...

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Autores principales: García-Corbacho, Javier, Indacochea, Alberto, González Navarro, Azucena E., Victoria, Iván, Moreno, Débora, Pesántez, David, Angelats, Laura, Modrego-Sanchez, Andrea, Sanfeliu, Esther, Castillo, Oleguer, Blasco, Paula, Mezquita, Laura, Viñolas, Nuria, Nogué, Miquel, Galván, Patricia, Adamo, Barbara, Basté, Neus, Sauri, Tamara, Juan, Manel, Prat, Aleix, Schettini, Francesco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10198872/
https://www.ncbi.nlm.nih.gov/pubmed/36625938
http://dx.doi.org/10.1007/s00262-022-03360-9
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author García-Corbacho, Javier
Indacochea, Alberto
González Navarro, Azucena E.
Victoria, Iván
Moreno, Débora
Pesántez, David
Angelats, Laura
Modrego-Sanchez, Andrea
Sanfeliu, Esther
Castillo, Oleguer
Blasco, Paula
Mezquita, Laura
Viñolas, Nuria
Nogué, Miquel
Galván, Patricia
Adamo, Barbara
Basté, Neus
Sauri, Tamara
Juan, Manel
Prat, Aleix
Schettini, Francesco
author_facet García-Corbacho, Javier
Indacochea, Alberto
González Navarro, Azucena E.
Victoria, Iván
Moreno, Débora
Pesántez, David
Angelats, Laura
Modrego-Sanchez, Andrea
Sanfeliu, Esther
Castillo, Oleguer
Blasco, Paula
Mezquita, Laura
Viñolas, Nuria
Nogué, Miquel
Galván, Patricia
Adamo, Barbara
Basté, Neus
Sauri, Tamara
Juan, Manel
Prat, Aleix
Schettini, Francesco
author_sort García-Corbacho, Javier
collection PubMed
description 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 < 0.001). Immunotherapy-naïve status was independently associated with better PFS (p = 0.005). Time-to-best response (TTBR) and ORR (p < 0.001 both) were associated with better OS at univariate analysis. PFS and DOR were moderately correlated with OS (p < 0.001 both). A PD-L1 10% cut-off detected worse/best responders in terms of ORR (univariate p = 0.011, multivariate 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00262-022-03360-9.
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spelling pubmed-101988722023-05-21 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 García-Corbacho, Javier Indacochea, Alberto González Navarro, Azucena E. Victoria, Iván Moreno, Débora Pesántez, David Angelats, Laura Modrego-Sanchez, Andrea Sanfeliu, Esther Castillo, Oleguer Blasco, Paula Mezquita, Laura Viñolas, Nuria Nogué, Miquel Galván, Patricia Adamo, Barbara Basté, Neus Sauri, Tamara Juan, Manel Prat, Aleix Schettini, Francesco Cancer Immunol Immunother Research 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 < 0.001). Immunotherapy-naïve status was independently associated with better PFS (p = 0.005). Time-to-best response (TTBR) and ORR (p < 0.001 both) were associated with better OS at univariate analysis. PFS and DOR were moderately correlated with OS (p < 0.001 both). A PD-L1 10% cut-off detected worse/best responders in terms of ORR (univariate p = 0.011, multivariate 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00262-022-03360-9. Springer Berlin Heidelberg 2023-01-10 2023 /pmc/articles/PMC10198872/ /pubmed/36625938 http://dx.doi.org/10.1007/s00262-022-03360-9 Text en © The Author(s) 2023, corrected publication 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research
García-Corbacho, Javier
Indacochea, Alberto
González Navarro, Azucena E.
Victoria, Iván
Moreno, Débora
Pesántez, David
Angelats, Laura
Modrego-Sanchez, Andrea
Sanfeliu, Esther
Castillo, Oleguer
Blasco, Paula
Mezquita, Laura
Viñolas, Nuria
Nogué, Miquel
Galván, Patricia
Adamo, Barbara
Basté, Neus
Sauri, Tamara
Juan, Manel
Prat, Aleix
Schettini, Francesco
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10198872/
https://www.ncbi.nlm.nih.gov/pubmed/36625938
http://dx.doi.org/10.1007/s00262-022-03360-9
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