BackgroundHigh tumor mutational burden (TMB-H) is correlated with enhanced objective response rate (ORR) and progression-free survival (PFS) for certain cancers receiving immunotherapy. This study aimed to investigate the safety and efficacy of toripalimab, a humanized programmed death-1 (PD-1) antibody, in advanced gastric cancer (AGC), and the predictive survival benefit of TMB and PD-L1.Patients and methodsWe reported on the AGC cohort of phase Ib/II trial evaluating the safety and activity of toripalimab in patients with AGC, oesophageal squamous cell carcinoma, nasopharyngeal carcinoma and head and neck squamous cell carcinoma. In cohort 1, 58 chemo-refractory AGC patients received toripalimab (3 mg/kg d1, Q2W) as a monotherapy. In cohort 2, 18 chemotherapy-naive AGC patients received toripalimab (360 mg d1, Q3W) with oxaliplatin 130 mg/m2 qd, d1, capecitabine 1000 mg/m2 b.i.d., d1–d14, Q3W as first-line treatment. Primary end point was ORR. Biomarkers such as PD-L1 and TMB were evaluated for correlation with clinical efficacy.ResultsIn cohort 1, the ORR was 12.1% and the disease control rate (DCR) was 39.7%. Median PFS was 1.9 months and median OS was 4.8 months. The TMB-H group showed significant superior OS than the TMB-L group [14.6 versus 4.0 months, HR = 0.48 (96% CI 0.24–0.96), P = 0.038], while PD-L1 overexpression did not correlate with significant survival benefit. A 77.6% of patients experienced at least one treatment-related adverse event (TRAE), and 22.4% of patients experienced a grade 3 or higher TRAE. In cohort 2, the ORR was 66.7% and the DCR was 88.9%. A 94.4% of patients experienced at least one TRAE and 38.9% of patients experienced grade 3 or higher TRAEs.ConclusionsToripalimab has demonstrated a manageable safety profile and promising antitumor activity in AGC patients, especially in combination with XELOX. High TMB may be a predictive marker for OS of AGC patients receiving toripalimab as a single agent.Trial registrationClinicalTrials.gov NCT02915432.

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The prevention of chemotherapy‐induced nausea and vomiting was one of the most challenging supportive care issues in oncology, especially to highly emetogenic chemotherapy (HEC). A total of 645 patients were randomized into fosaprepitant group (fosaprepitant/placebo 150 mg d1 in combination with granisetron and dexamethasone) or aprepitant group (aprepitant/placebo 125 mg d1; 80 mg d2‐d3 plus granisetron and dexamethasone).The primary endpoint was the percentage of patients who had a complete response (CR) over the entire treatment course (0–120 hr, overall phase [OP]). It was assessed by using a non‐inferiority model, with a non‐inferiority margin of 10%. The difference of the CR rate was compared between two groups with chi‐square analysis. Six hundred and twenty‐six patients were included in the per protocol analysis. The percentage of patients with a CR in the fosaprepitant group was not inferior to that in the aprepitant group (90.85% versus 94.17%, p = .1302) during OP. Whether the cisplatin‐based chemotherapy or not, the CR rate of the fosaprepitant group was not inferior to that of the aprepitant group. Both regimens were well tolerated. The most common adverse event was constipation. Fosaprepitant provided effective and well‐tolerated control of nausea and vomiting associated with HEC in Chinese patients.

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Background Triple-negative breast cancer (TNBC) is an aggressive cancer that affects about 13/100,000 women yearly. Patients with TNBC are often resistant to endocrine and molecular targeted therapy, making clinical treatment challenging. Researches indicate that tumor microenvironment (TME) is related to prognosis in many cancers. Therefore, we aim to identify TME immune-related biomarkers to enhance the prognosis and immunotherapy efficacy in patients with TNBC. Methods The bulk mRNA transcriptome data and clinical information of the (GSE58812) and (GSE25055) datasets were downloaded from the Gene Expression Omnibus (GEO) database, and the ESTIMATE algorithm was used to calculate the ImmuneScore, StromalScore, and ESTIMATEScore. Patients were divided into low and high groups according to the quartiles of ImmuneScore, StromalScore, and the median of ESTIMATEScore to filter differential expression genes (DEGs), respectively. The DEGs were then evaluated using univariate and multivariate Cox regression to identify TME-related genes and its association with survival rate for the construction of a TMErisk model with three biomarkers. Then Gene Expression Profiling Interactive Analysis (GEPIA) and The Cancer Genome Atlas (TCGA) data were used to compare the gene expression in cancer and normal tissues. xCell analysis calculated the proportion of tumor-infiltrating immune cells in low and high expression of ATPase Secretory Pathway Ca 2+ Transporting 2 ( ATP2C2 ). In addition, samples from 20 TNBC patients admitted to our institution were used for immunohistochemical (IHC) examination. Results Three immune-related DEGs were identified, including prolyl 3-hydroxylase 2 ( P3H2 ), sodium voltage-gated channel beta subunit 3 ( SCN3B ), and ATP2C2 and a TMErisk model was constructed and validated. However, only ATP2C2 was selected for further analysis. ATP2C2 mRNA level of TNBC patients was higher than that of normal breast tissue. Survival analysis showed that patients with high expression of ATP2C2 had a bad prognosis. xCell analysis demonstrated that the expression of ATP2C2 was associated with 16 kinds of tumor-infiltrating immune cells. Protein expression of ATP2C2 in TNBC tissues was higher compared to paired normal tissues in IHC. Conclusions This study constructed and validated a TMErisk model that can effectively predict 3- and 5-year survival rate for TNBC patients. TNBC patients with lower expression of ATP2C2 had a good prognosis.