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Background Neuroendocrine neoplasms (NENs) are a group of diseases that show high heterogeneity but have limited treatment options. This phase I study evaluated the safety and efficacy of sintilimab, anti-PD-1 monoclonal antibody, in treating advanced NENs. Methods We prospectively enrolled patients pathologically diagnosed with NENs after standard treatment failure. Neuroendocrine neoplasms were classified into well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine cancers (NECs). Every patient received sintilimab, and response was assessed every 9 weeks. Results Twenty-four patients with a median age of 57.0 years were enrolled from November 2016 to 2017. The median Ki-67 index was 60%. Five patients had NET, 1 had NET G3, 17 had NEC, and 1 had mixed adenocarcinoma-neuroendocrine carcinoma. The most common primary tumor sites were the pancreas and gastrointestinal tract in 7 and 10 patients, respectively. In phase Ia trial, 2 patients received sintilimab 1 mg/kg every 2 weeks, one received 3 mg/kg every 2 weeks, and 21 patients enrolled in the phase Ib trial received 200 mg every 3 weeks. The objective response rate was 20.8% in all enrolled patients and 27.8% in NEC patients. The median progression-free survival was 2.2 and 2.1 months in patients with NET and NEC, respectively. The median OS was not applicable (NA) and 10.8 months (95% CI, 4.3, NA) with NET and NEC, respectively. The duration of response (DOR) was not reached, with a median follow-up time of 20.7 months. Treatment-related adverse events (TRAE) occurred in 17 (70.8%) patients. The most frequent TRAE was thyroid dysfunction (41.7%), and a grade 3 pulmonary infection occurred in 1 patient. The programmed cell death 1-ligand 1 (PD-L1)-positive (tumor proportion score ≥1%) rate was 18.8% (3 out of 16) and the expression of PD-L1 did not correlate with response. Conclusion Sintilimab was well-tolerated and showed encouraging response in NECs. ClinicalTrials.gov Identifier NCT02937116. [ABSTRACT FROM AUTHOR]

Background: Real‐world safety and effectiveness data for trastuzumab plus chemotherapy treatment of patients with HER2‐positive metastatic gastric cancer (mGC) in China are lacking. Patients and Methods: EVIDENCE was a prospective, multicenter, noninterventional registry study evaluating the safety and effectiveness of trastuzumab in five cohorts of Chinese patients with gastric cancer, stratified by HER2 status and trastuzumab treatment. Effectiveness was analyzed for cohorts I (HER2‐positive, trastuzumab treated), II (HER2‐positive, trastuzumab untreated), and IV (HER2‐negative, trastuzumab untreated); trastuzumab‐related adverse events (AEs) were analyzed for cohort I. Results: Cohorts I, II, and IV included 174, 113, and 422 patients, respectively. Most patients received first‐line chemotherapy (87.6%). Median overall survival (OS1) for first‐line treatment was 22.3, 17.2, and 17.4 months in cohorts I, II, and IV, respectively. After excluding patients who had surgery, respective median OS1 was 19.9, 15.3, and 12.9 months. Respective first‐line progression‐free survival (PFS1) was 8.2, 6.9, and 6.2 months; and respective first‐line response rates (RR) were 51.7%, 18.4%, and 32.8%. Cohort I was significantly favored over cohort II for propensity score–matched first‐line median OS1 (hazard ratio [HR], 0.61), PFS1 (HR, 0.64), and RR (odds ratio, 4.93). Trastuzumab‐related AEs, grade 3–5 AEs, serious AEs, and AEs with a fatal outcome occurred in 23.6%, 3.4%, 2.3%, and 0.6% of cohort I patients, respectively. Conclusion: Safety profiles were consistent with those known for trastuzumab and chemotherapy; trastuzumab treatment improved outcomes. Our study provides real‐world data supporting first‐line trastuzumab plus chemotherapy in Chinese patients with HER2‐positive mGC. Implications for Practice: This prospective, noninterventional registry study aimed to provide safety and effectiveness data for the use of trastuzumab in combination with chemotherapy in Chinese patients with HER2‐positive metastatic gastric cancer (mGC) from the real‐world clinical setting. Trastuzumab plus first‐line chemotherapy was shown to be safe and to improve outcomes when compared with patients treated with chemotherapy alone. Trastuzumab was effective within a range of treatment regimens; subgroup analysis showed that trastuzumab paired most effectively with the XELOX regimen. This study provides real‐world clinical safety and effectiveness data supporting the use of trastuzumab in the treatment of Chinese patients with HER2‐positive mGC. This article reports the results of the EVIDENCE study, which evaluated the effectiveness and safety of trastuzumab in patients with HER2‐positive metastatic gastric cancer in a real‐world setting in China. [ABSTRACT FROM AUTHOR]

Background. To observe the efficacy, safety, and optimal dosage of recombinant antitumor and antivirus protein (Novaferon) in treating patients with metastatic colorectal cancer (mCRC) who failed at least two prior palliative regimens. Methods. We enrolled 108 patients from May 2011 to December 2012. According to different treatment modalities and therapeutic dosages, the participants were randomly divided into four cohorts at a 2:2:2:1 ratio: (a) 20 µg Novaferon (Genova Biotech, Beijing, People's Republic of China, http://www.genovabiotech.net) injected twice per week, (b) 20 µg Novaferon injected 3 times per week, (c) 40 µg Novaferon injected 3 times per week, or (d) saline injected 3 times per week. The primary endpoint was overall survival. Results. There was no significant difference in overall survival among the four cohorts. The 20-µg dose of Novaferon injected 3 times per week had the highest disease control rate (44.0%) at 6 weeks but without significant differences when compared with placebo (p = .159). Major adverse events with Novaferon were influenza-like symptoms, bone marrow suppression, liver dysfunction, and gastrointestinal discomfort. The level of natural killer cells increased and regulatory T cells decreased significantly after treatment with Novaferon, whereas levels in he placebo group remained the same. Conclusion. Novaferon showed moderate efficacy and was well tolerated in patients with mCRC, especially with the 20-µg dose injected 3 times per week. Furthermore, Novaferon might improve immune function of these patients. [ABSTRACT FROM AUTHOR]