However, no previous reports have compared the efficacy of anti\PD\1 antibodies between NSCLC patients with and without MPE. and a poor performance status (PS) were all correlated with a lower efficacy of PD\1/PD\L1 checkpoint inhibitors, compared to wild\type, Sinomenine hydrochloride smoker status, and a good PS, respectively.10, 11, 12, 13, 14, 15 A previous study also reported that the presence of liver or lung metastases was a negative predictor of anti\PD\1 efficacy in patients with advanced NSCLC. However, no previous reports have compared the efficacy of anti\PD\1 antibodies between NSCLC patients with and without MPE. Thus, we retrospectively investigated the efficacy of anti\PD\1 antibodies in advanced NSCLC patients with or without MPE. Methods Patients We retrospectively reviewed the medical records of patients with advanced or recurrent NSCLC who received nivolumab or pembrolizumab as first, second, or third\line treatment between 1 December 2015 and 31 March 2018 at the National Cancer Center Hospital, Japan. The end of the follow\up period was 31 Sinomenine hydrochloride July 2018. Patients with positive pleural fluid cytology results, pleural effusion requiring drainage, or presenting with multiple pleural nodules and nodular pleural thickening with pleural effusion on a computed tomography (CT) scan were diagnosed as having MPE. We diagnosed the presence of MPE before commencing anti\PD\1 antibody treatment. Tumor response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 using CT images. We did not consider an increase in pleural effusion as a progressive event. PFS was defined as the interval between the first dose of anti\PD\1 antibody treatment and the date of clinical or radiographic disease progression or death from any cause; in the absence of confirmation of disease progression or death, data were censored at the last date the patient was known to be alive. OS was defined as the interval between the first dose of anti\PD\1 antibody treatment and the date of death from any cause; in the absence of confirmation of death, data were censored at the last date the patient was known to be alive. PD\L1 expression in the tumor cells of patients with NSCLC was analyzed using the commercially available PD\L1 immunohistochemistry 22C3 pharmDx assay (Dako; Agilent Technologies, Santa Clara, CA, USA).16 Positive PD\L1 expression in 1% of all tumor cells was classified as a positive result, while positive PD\L1 expression in 50% was classified as strongly positive, consistent with the methodology used in other studies involving anti\PD\1 antibodies (Fig ?(Fig11).1, 17, 18 Open in a separate window Figure 1 Immunohistochemical analysis of PD\L1 expression in (a) strongly positive (?50%) and (b) positive (?1%) tumor cells. Statistical analysis Baseline characteristics were compared between patients with and without MPE using the Fisher’s exact test for categorical variables. PFS and OS curves were estimated using the KaplanCMeier method, and variations according to the absence or presence of MPE ER81 were evaluated using a log\rank test. Univariate and multivariate analyses were performed using Cox proportional risk regression models for performance status, smoking status, mutational status, PD\L1 expression status, treatment collection, and the presence of MPE. The covariates other than MPE were used based on the results of recent tests suggesting that they might affect the effectiveness of PD\1/PD\L1 checkpoint inhibitors.1, 11, 13, 14, 15, 17, 19, 20 All ideals were based on a one\sided hypothesis, and ideals 0.05 were considered statistically significant. All statistical analyses were performed using JMP Pro version 13.0.0 (SAS Institute, Cary, NC, USA). Results Patient characteristics A total of 252 individuals with advanced or recurrent NSCLC given nivolumab or pembrolizumab were recognized. The patient characteristics are summarized in Table ?Table1.1. Twelve percent of the individuals experienced an Eastern Cooperative Oncology Group PS of 2, 19% were by no means\smokers, 7.9% had mutations, 13% had a Sinomenine hydrochloride PD\L1 negative status, and 84% received an anti\PD\1 antibody as second or third\line treatment. Sinomenine hydrochloride Of the 252 individuals, 33 individuals experienced MPE (cytologically confirmed malignant cells, mutated20 (7.9)17 (7.8)3 (9.1)0.61PD\L1 22C3 status0.33 1%33 (13)27 (12)6 (18) 1%132 (52)114 (52)18 (55)Mind metastasis55 (22)50 (23)5 (15)0.23Treatment collection0.062141 (16)32 (15)9 (27)2/3211 (84)187 (85)24 (73)Anti\PD\1 antibody0.34Nivolumab179 (71)157 (72)22 (67)Pembrolizumab73 (29)62 (28)11 (33) Open in a separate windowpane ECOG PS, Eastern Cooperative Oncology Group performance status. Efficacy The overall response rate (ORR) was related in individuals with and without MPE (ORR 24% vs. 26%; = 1.00). The PFS and OS of individuals with MPE were significantly shorter than in individuals without MPE (median PFS 3.0 vs. 5.8?weeks,.