Pretreatment Blood Parameters Predict Efficacy from Immunotherapy Agents in Early Phase Clinical Trials.
Journal
The oncologist
ISSN: 1549-490X
Titre abrégé: Oncologist
Pays: England
ID NLM: 9607837
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
04
06
2020
accepted:
21
07
2020
pubmed:
14
8
2020
medline:
22
5
2021
entrez:
14
8
2020
Statut:
ppublish
Résumé
Peripheral blood parameters are correlated to immune-checkpoint inhibitor efficacy in solid tumors, such as melanoma and non-small cell lung cancer. Few data are currently available on the prognostic role of these immune-inflammatory biomarkers for other solid tumors and immunotherapy combinations. From August 2014 to May 2019, 153 patients with metastatic solid tumors were enrolled in phase I clinical trials testing immunotherapy both as single agents and as combinations. Primary endpoint was to evaluate the impact of baseline blood parameters on progression-free survival (PFS) and overall survival (OS). The most common tumor types were gastrointestinal, breast, and gynecological cancers (22.9%, 22.2%, and 15.0%, respectively). Higher lactate dehydrogenase (LDH) and derived neutrophil-to-lymphocyte ratio (dNLR) were independently associated with reduced PFS (hazard ratio [HR], 1.97; 95% confidence interval [CI], 1.30-2.99; p = .001, and HR, 2.29; 95% CI, 1.39-3.77; p = .001, respectively) and reduced OS (HR, 2.04; 95% CI, 1.26-3.28; p = .004, and HR, 2.06; 95% CI, 1.12-3.79; p = .02, respectively). In the subgroup analysis, (single agent vs. combination), patients at "good" (dNLR <3 and LDH < upper limit of normal [ULN]) and "intermediate and poor" (dNLR >3 and/or LDH > ULN) risk had higher and lower PFS, respectively (p for interaction = .002). Conversely, patients receiving monotherapy presented statistically significant difference in OS according to the risk group, whereas this effect was not observed for those treated with combinations (p for interaction = .004). Elevated LDH and dNLR are associated with poorer survival outcomes in patients treated with immunotherapy in phase I clinical trials, regardless of tumor type. These parameters represent an easy tool that might be considered as stratification factors in immunotherapy-based clinical trials. In this retrospective cohort study of 153 patients with metastatic solid tumors treated with immunotherapy in the context of phase I clinical trials, elevated baseline lactate dehydrogenase and derived neutrophil-to-lymphocyte ratio were associated with reduced survival regardless of tumor subtype. If prospectively validated, these parameters might represent low-cost and easy biomarkers that could help patient selection for early phase immunotherapy trials and be applied as a stratification factor in randomized studies testing immunotherapy agents.
Sections du résumé
BACKGROUND
Peripheral blood parameters are correlated to immune-checkpoint inhibitor efficacy in solid tumors, such as melanoma and non-small cell lung cancer. Few data are currently available on the prognostic role of these immune-inflammatory biomarkers for other solid tumors and immunotherapy combinations.
MATERIAL AND METHODS
From August 2014 to May 2019, 153 patients with metastatic solid tumors were enrolled in phase I clinical trials testing immunotherapy both as single agents and as combinations. Primary endpoint was to evaluate the impact of baseline blood parameters on progression-free survival (PFS) and overall survival (OS).
RESULTS
The most common tumor types were gastrointestinal, breast, and gynecological cancers (22.9%, 22.2%, and 15.0%, respectively). Higher lactate dehydrogenase (LDH) and derived neutrophil-to-lymphocyte ratio (dNLR) were independently associated with reduced PFS (hazard ratio [HR], 1.97; 95% confidence interval [CI], 1.30-2.99; p = .001, and HR, 2.29; 95% CI, 1.39-3.77; p = .001, respectively) and reduced OS (HR, 2.04; 95% CI, 1.26-3.28; p = .004, and HR, 2.06; 95% CI, 1.12-3.79; p = .02, respectively). In the subgroup analysis, (single agent vs. combination), patients at "good" (dNLR <3 and LDH < upper limit of normal [ULN]) and "intermediate and poor" (dNLR >3 and/or LDH > ULN) risk had higher and lower PFS, respectively (p for interaction = .002). Conversely, patients receiving monotherapy presented statistically significant difference in OS according to the risk group, whereas this effect was not observed for those treated with combinations (p for interaction = .004).
CONCLUSION
Elevated LDH and dNLR are associated with poorer survival outcomes in patients treated with immunotherapy in phase I clinical trials, regardless of tumor type. These parameters represent an easy tool that might be considered as stratification factors in immunotherapy-based clinical trials.
IMPLICATIONS FOR PRACTICE
In this retrospective cohort study of 153 patients with metastatic solid tumors treated with immunotherapy in the context of phase I clinical trials, elevated baseline lactate dehydrogenase and derived neutrophil-to-lymphocyte ratio were associated with reduced survival regardless of tumor subtype. If prospectively validated, these parameters might represent low-cost and easy biomarkers that could help patient selection for early phase immunotherapy trials and be applied as a stratification factor in randomized studies testing immunotherapy agents.
Identifiants
pubmed: 32785940
doi: 10.1634/theoncologist.2020-0518
pmc: PMC7648370
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1732-e1742Informations de copyright
© AlphaMed Press 2020.
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