Phase I study of chimeric antigen receptor modified T cells in treating HER2-positive advanced biliary tract cancers and pancreatic cancers

This phase I clinical trial (NCT01935843) is to evaluate the safety, feasibility, and activity of chimeric antigen receptor-engineered T cell (CART) immunotherapy targeting human epidermal growth factor receptor 2 (HER2) in patients with advanced biliary tract cancers (BTCs) and pancreatic cancers (PCs). Eligible patients with HER2-positive (>50%) BTCs and PCs were enrolled in the trial. Well cultured CART-HER2 cells were infused following the conditioning treatment composed of nab-paclitaxel (100-200 mg/m) and cyclophosphamide (15-35 mg/kg). CAR transgene copy number in the peripheral blood was serially measured to monitor the expansion and persistence of CART-HER2 cells in vivo. Eleven enrolled patients received 1 to 2-cycle CART-HER2 cell infusion (median CAR T cell 2.1 × 10/kg). The conditioning treatment resulted in mild-to-moderate fatigue, nausea/vomiting, myalgia/arthralgia, and lymphopenia. Except one grade-3 acute febrile syndrome and one abnormal elevation of transaminase (>9 ULN), adverse events related to the infusion of CART-HER2 cells were mild-to-moderate. Post-infusion toxicities included one case of reversible severe upper gastrointestinal hemorrhage which occurred in a patient with gastric antrum invaded by metastasis 11 days after the CART-HER2 cell infusion, and 2 cases of grade 1-2 delayed fever, accompanied by the release of C-reactive protein and interleukin-6. All patients were evaluable for assessment of clinical response, among which 1 obtained a 4.5-months partial response and 5 achieved stable disease. The median progression free survival was 4.8 months (range, 1.5-8.3 months). Finally, data from this study demonstrated the safety and feasibility of CART-HER2 immunotherapy, and showed encouraging signals of clinical activity.

Comparison of clinicopathological features and prognosis in triple-negative and non triple-negative breast cancer / 中华内分泌外科杂志

ObjectiveTo find out the incidence of triple-negative breast cancer(TNBC) in all kinds of breast cancers.To compare and analyze the clinicopathological features,recurrence,metastasis,and prognosis of patients with TNBC and non-triple negative breast cancer (non-TNBC).MethodsThe clinicopathological features and follow-up data of 387 patients with primary breast cancer histopathologically conffirmed in our hospital from Sep.2004 to Sep.2006 were retrospectively analyzed.The 387 patients were divided into 2 groups:79 cases of TNBC and 308 cases of non-TNBC.The clinical features and prognosis of the 2 groups were compared.Results Compared with non-TNBC group,patients in TNBC group had their special features:1.higher ratio of patients ＜ 35 years( P =0.012 ) ; 2.higher ratio of patients with family history of breast cancer( P =0.031 ) ; 3.higher ratio of tumors with maximum diameter ≥ 5 cm ( P =0.044 ) ; 4. higher ratio of patients with positive lymph nodes(P =0.011 ) ; 5.higher ratio of tumors in clinical stage Ⅲ(P =0.007) ; 6.higher ratio of tumors in histological stage Ⅲ(P =0.028 ).The 5-year-disease-free survival (DFS) and overall survival (OS) rate for patients with TNBC were 72.15％ and 88.61％ respectively,lower than those of non-TNBC ( P =0.003 and 0.031 respectively).ConclusionsCompared with non-TNBC patients,patients with TNBC have the features of younger age,more advanced clinical stage upon diagnose,higher rate of lymph node metastasis,larger tumors,higher histological grade,faster and easier recurrence and metastasis,and lower rate of DFS and OS.The information of age,the maximum diameter of the tumor,lymph node status,clinical stage,histological grade and pathological types,especially the age and lymph node status,play an important role in predicting the prognosis of TNBC.