All patients received a platinum-based doublets chemotherapy. After a median follow-up of 18.7 mo, mPFS and mOS were 4.3 (95% CI 2.7C6.4) and 11.4 (95% CI 7.7C13.3) mo, respectively. that is markedly up-regulated during various inflammatory conditions [25]. In cancer patients, elevated levels of this protein are not only exclusively connected to the physiological tumour-related inflammation, but also reflect a specific tumour production as potential mechanism of immune evasion, considering the relevant immune-modulating properties of SAA [26]. In this study, we evaluated the association between blood SAA levels and clinical benefit in advanced NSCLC patients during treatment with first-line pembrolizumab, with the final aim to investigate if SAA could represent a potential predictive biomarker for response to anti-PD-1 brokers. Methods In this exploratory, observational, prospective, single-center study, blood SAA was collected to be evaluated as a candidate biomarker for first-line pembrolizumab (200?mg iv every 3?weeks) in patients with histologically or cytologically confirmed stage IV NSCLC with PD-L1 TPS of 50% or greater and no sensitizing mutations or and translocations (P cohort). A control cohort of patients with advanced NSCLC and PD-L1 TPS ranges from 0 to 49%, exclusively treated with chemotherapy (CT Cohort), were also prospectively evaluated for SAA. Patients of both cohorts received the treatments at Fondazione Policlinico Universitario A. Gemelli IRCCS. Patients entry criteria According to inclusion criteria, patients had undergone no previous systemic therapy for metastatic disease, and had an Eastern Cooperative Oncology OSMI-4 Group (ECOG) performance-status (PS) score of 0 or 1 (on a 5-point scale, with 0 indicating no symptoms and higher scores indicating increasing disability). At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) and adequate hematologic, hepatic, and renal functions were required, in addition to normal basal levels of TSH, fT3, fT4 and ACTH for the P cohort. Exclusion criteria for receiving pembrolizumab were symptomatic interstitial lung diseases, autoimmune diseases and systemic immunosuppression. Patients with brain metastases were eligible if asymptomatic or already treated with cranial radiotherapy. Progression was defined according to RECIST 1.1 criteria. CT scan evaluation was performed by a designated radiologist at baseline and every 9?weeks during the treatment. PD-L1 expression was assessed Rabbit polyclonal to PLD4 in formalin-fixed tumor samples at local laboratory by a designated pathologist with the use of the commercially available PD-L1 IHC 22C3 pharmDx assay (Dako North America). All adverse events were graded according to the National Malignancy Institute Common Terminology Criteria for Adverse Events, version 4.0. Study protocol was reviewed and approved by the local institutional review board and Ethical Committee (Prot. 26,496/19, ID 2640, June 20th, 2019) and conducted according to the principles of Declaration of Helsinki and EU General Data Protection Regulation (GDPR, 25.05.18). Patients enrolled in the study signed a written informed consent for biomarkers analysis and clinical data collection OSMI-4 at the beginning of therapy. Patients data were anonymized before analysis. SAA assessment Blood samples were collected at baseline (day of the first administration of pembrolizumab), before the start of the infusion for both cohorts; the same procedure was performed every 9?weeks OSMI-4 in the only P cohort until withdrawal from treatment for either toxicity or disease progression. SAA plasma concentration was measured by a commercial enzyme-linked immunosorbent assay (ELISA) (Siemens Healthineers, Milano, Italy). Endpoints and statistical analysis No power analysis was done to calculate the sample size given the explorative and initial aim of the study. The primary end-point response rate (RR) was calculated as the proportion of partial and complete responses assessed by radiological imaging. The secondary end-points were progression-free survival (PFS), defined as the time from randomization until first evidence of objective tumor progression or death from any cause and overall survival (OS), as the time from starting treatment to death for any cause. The endpoints were evaluated according to the SAA value at baseline in both cohorts and during treatment only in the P cohort. SSA was analyzed both as continuous and discontinuous variable (low OSMI-4 versus high), using a prefixed threshold value. ROC curve analysis was used to determine the value of SAA levels to adopt as cut-off, which more accurately predict response to pembrolizumab. The association of SAA level with clinico-pathological characteristics and RR was evaluated by Fishers exact test, number After a median (m) follow-up time of 18.5 mo, the mPFS of overall population was 8 (95% CI 4.4C17.4) mo. The.