Purpose: No antiangiogenic treatment is yet approved for extrapancreatic neuroendocrine tumors (NET). Surufatinib (HMPL-012, previously named sulfatinib) is a small-molecule inhibitor targeting vascular endothelial growth factor receptors, fibroblast growth factor receptor 1 and colony-stimulating factor 1 receptor. We conducted a single-arm phase Ib/II study of surufatinib in advanced NETs.Patients and Methods: Patients with histologically welldifferentiated, low or intermittent grade, inoperable or metastatic NETs were enrolled into a pancreatic or extrapancreatic NET cohort. Patients were treated with surufatinib 300 mg orally, once daily. The primary endpoints were safety and objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (version 1.1).Results: Of the 81 patients enrolled, 42 had pancreatic NETs and 39 had extrapancreatic NETs. Most patients had radiologic progression within 1 year prior to enrollment (32 patients in each cohort). In the pancreatic and extrapancreatic NET cohorts, ORRs were 19% [95% confidence intervals (CI), 9-34] and 15% (95% CI, 6-31), disease control rates were 91% (95% CI, 77-97) and 92% (95% CI, 79-98), and median progression-free survival was 21.2 months (95% CI, 15.9-24.8) and 13.4 months (95% CI, 7.6-19.3), respectively. The most common grade !3 treatment-related adverse events were hypertension (33%), proteinuria (12%), hyperuricemia (10%), hypertriglyceridemia, and diarrhea (6% for each), and increased alanine aminotransferase (5%).Conclusions: Surufatinib showed encouraging antitumor activity and manageable toxicities in patients with advanced NETs. Two ongoing phase III studies, validating the efficacy of surufatinib in patients with NETs, will contribute to the clinical evidence.

Purpose RC48 contains the novel humanized anti-HER2 antibody hertuzumab conjugated to MMAE via a cleavable linker. A phase I study was initiated to evaluate the toxicity, MTD, PK, and antitumor activity of RC48 in patients with HER2-overexpressing locally advanced or metastatic solid carcinomas, particularly gastric cancer. Patients and methods This was a 2-part phase I study. Successive cohorts of patients received escalating doses of RC48 (0.1 mg/kg, 0.5 mg/kg, 1.0 mg/kg, 2.0 mg/kg, 2.5 mg/kg, and 3.0 mg/kg). Dose expansion proceeded at the dose of 2.0 mg/kg Q2W. The efficacy and safety set included all patients who received at least one dose of RC48. Results Fifty-seven patients were enrolled, the MTD was unavailable due to termination of 3.0 mg/kg cohort; 2.5 mg/kg Q2W was declared the RP2D. RC48 was well tolerated, the most frequent grade 3 or worse TRAEs included neutropenia (19.3%), leukopenia (17.5%), hypoesthesia (14.0%), and increased conjugated blood bilirubin (8.8%). Four deaths occurred during the whole study, three of which were believed to be related to RC48. Overall, ORR and DCR were 21.0% (12/57) and 49.1% (28/57). Notably, patients who were HER2 IHC2+/FISH- responded similarly to those who were IHC2+/FISH+ and IHC3+, with ORRs of 35.7% (5/14), 20% (2/10), and 13.6% (3/22), respectively. In patients who were pretreated with HER2-targeted drugs, RC48 also showed promising efficacy, with ORR of 15.0% (3/20) and DCR of 45.0% (9/20). Conclusion RC48 was well tolerated and showed promising antitumor activity in HER2-positive solid tumors, including gastric cancer with HER2 IHC 2+/FISH- status. Clinical trial information NCT02881190.

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Background: The prognostic value of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio, and the combined NLR-PLR score in patients with stage IV gastric carcinoma (GC) has not yet been clarified. Therefore, this study aimed to explore the potential association of NLR, PLR, and NLR-PLR score with the prognosis of patients with stage IV GC. Methods: This retrospective study included 466 patients with GC diagnosed between 2010 and 2017. High NLR and high PLR were defined using the median values as the cutoff values. We then combined the NLR and PLR value and generated the NLR-PLR score as a new biomarker. Patients were divided into three groups according to their NLR-PLR score. Univariate and multivariate analyses were conducted to compare survival outcomes. Results: Median overall survival (OS) and progression-free survival (PFS) were 15.5 months (range, 0.7-96.8 months) and 6.7 months (range, 0.5-30.4 months), respectively. The NLR, PLR, and the NLR-PLR scores were correlated with clinical outcomes such as OS and PFS. Median OS for patients with NLR-PLR scores of 0, 1, and 2 was 22.5, 15.7, and 11.2 months, respectively. Median PFS for patients with these NLR-PLR scores of 0, 1, and 2 was 7.8, 7.1, and 5.2 months, respectively (P < 0.001). High NLR-PLR scores predicted poor survival in patients with stage IV GC (all P < 0.05). Conclusion: Our findings provide scientific evidence to support that the NLR-PLR score may be able to independently predict survival outcomes in patients with stage IV GC.

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