Open AccessPretreatment Blood Parameters Predict Efficacy from Immunotherapy Agents in Early Phase Clinical Trials
Author(s) -
Criscitiello Carmen,
Marra Antonio,
Morganti Stefania,
Zagami Paola,
Viale Giulia,
Esposito Angela,
Curigliano Giuseppe
Publication year - 2020
Publication title -
the oncologist
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.176
H-Index - 164
eISSN - 1549-490X
pISSN - 1083-7159
DOI - 10.1634/theoncologist.2020-0518
Subject(s) - medicine , hazard ratio , clinical endpoint , confidence interval , gastroenterology , immunotherapy , oncology , lung cancer , lactate dehydrogenase , melanoma , clinical trial , cancer , cancer research , biochemistry , chemistry , enzyme
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.