PMID- 31451841 OWN - NLM STAT- MEDLINE DCOM- 20191028 LR - 20240426 IS - 1432-0851 (Electronic) IS - 0340-7004 (Print) IS - 0340-7004 (Linking) VI - 68 IP - 9 DP - 2019 Sep TI - Safety and efficacy of PD-1 blockade-activated multiple antigen-specific cellular therapy alone or in combination with apatinib in patients with advanced solid tumors: a pooled analysis of two prospective trials. PG - 1467-1477 LID - 10.1007/s00262-019-02375-z [doi] AB - BACKGROUND: The lethal effects of multiple antigen-specific cellular therapy (MASCT) may be enhanced by blocking PD-1 in vitro and vascular endothelial growth factor receptor 2 inhibitor (apatinib). We analyzed the pooled data from our phase I/II trials to determine the toxicity and efficacy of PD-1 blockade (SHR-1210)-activated MASCT (aMASCT) alone or in combination with apatinib in advanced solid tumors. METHODS: Patients with advanced solid tumors received aMASCT alone (n = 32) or aMASCT plus apatinib (500 mg q.d., n = 38) after standard treatment. The safety profile was the primary end point. The secondary end points were antitumor response, progression-free survival (PFS), and overall survival (OS). The circulating T cells were quantified before and after aMASCT infusion. RESULTS: Treatment-related adverse events (AEs) occurred in 18/32 (56.3%) and 25/38 (65.8%) patients in the aMASCT and aMASCT plus apatinib groups, respectively. No serious AEs were reported, and apatinib did not increase immunotherapy-related toxicity. The objective response rate (34.2% and 18.8%) and PFS (median 6.0 and 4.5 months, P = 0.002) were improved in the aMASCT plus apatinib group compared with the aMASCT group; however, the OS was not improved (median 10.0 and 8.2 months, P = 0.098). Multivariate analyses indicated that two or more cycles of aMASCT treatment was an independent and favorable prognostic factor of PFS and OS. The circulating T cells increased and Tregs decreased in both groups after one cycle of aMASCT treatment. CONCLUSIONS: Treatment with aMASCT plus apatinib was safe and effective for the management of advanced solid tumors. FAU - Liang, Lijun AU - Liang L AD - Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, No. 182 Tongguan North Road, Lianyungang, 222002, China. FAU - Wen, Yixuan AU - Wen Y AD - Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, No. 182 Tongguan North Road, Lianyungang, 222002, China. FAU - Hu, Rong AU - Hu R AD - Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China. FAU - Wang, Lei AU - Wang L AD - Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, No. 182 Tongguan North Road, Lianyungang, 222002, China. FAU - Xia, Youyou AU - Xia Y AD - Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, No. 182 Tongguan North Road, Lianyungang, 222002, China. FAU - Hu, Chenxi AU - Hu C AD - Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, No. 182 Tongguan North Road, Lianyungang, 222002, China. FAU - Qiao, Yun AU - Qiao Y AD - Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, No. 182 Tongguan North Road, Lianyungang, 222002, China. FAU - Geng, Xiaowei AU - Geng X AD - Department of Clinical Medicine, Xuzhou Medical University, Xuzhou, Jiangsu, China. FAU - Chen, Ting AU - Chen T AD - Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, No. 182 Tongguan North Road, Lianyungang, 222002, China. FAU - Fei, Jiayan AU - Fei J AD - Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, No. 182 Tongguan North Road, Lianyungang, 222002, China. FAU - Hui, Kaiyuan AU - Hui K AD - Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, No. 182 Tongguan North Road, Lianyungang, 222002, China. kyhui1987@163.com. FAU - Jiang, Xiaodong AU - Jiang X AD - Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, No. 182 Tongguan North Road, Lianyungang, 222002, China. jxdysy1970@163.com. LA - eng GR - BE2017684/Jiangsu Province Key Research and Development Plan (Social Development) Project/ GR - H2017039/Scientific Research Project of Jiangsu Health and Family Planning Commission/ GR - 81472792/National Natural Science Foundation of China/ GR - 81702813/National Natural Science Foundation of China/ GR - SJCX18_0707/Postgraduate Research & Practice Innovation Program of Jiangsu Province/ GR - SJCX19_0766/Postgraduate Research & Practice Innovation Program of Jiangsu Province/ GR - SH1613/Technology Office Foundation of Lianyungang City/ PT - Clinical Trial, Phase I PT - Clinical Trial, Phase II PT - Journal Article DEP - 20190827 PL - Germany TA - Cancer Immunol Immunother JT - Cancer immunology, immunotherapy : CII JID - 8605732 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Antigens, Neoplasm) RN - 0 (PDCD1 protein, human) RN - 0 (Programmed Cell Death 1 Receptor) RN - 0 (Pyridines) RN - 5S371K6132 (apatinib) RN - 73096E137E (camrelizumab) RN - EC 2.7.10.1 (ERBB2 protein, human) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antibodies, Monoclonal, Humanized/pharmacology/*therapeutic use MH - Antigens, Neoplasm/immunology MH - Antineoplastic Combined Chemotherapy Protocols/therapeutic use MH - Combined Modality Therapy MH - Dendritic Cells/*immunology/transplantation MH - Drug-Related Side Effects and Adverse Reactions MH - Female MH - Humans MH - Immunotherapy/*methods MH - Male MH - Middle Aged MH - Neoplasms/*drug therapy/immunology/mortality MH - Programmed Cell Death 1 Receptor/antagonists & inhibitors MH - Prospective Studies MH - Pyridines/pharmacology/*therapeutic use MH - Receptor, ErbB-2/antagonists & inhibitors MH - Survival Analysis MH - T-Lymphocytes, Cytotoxic/*immunology MH - T-Lymphocytes, Regulatory/*immunology PMC - PMC11028216 OTO - NOTNLM OT - Anti-angiogenic drugs OT - Apatinib OT - DC-CIK OT - PD-1 blockade OT - Safety COIS- The authors declare that they have no conflict of interest. EDAT- 2019/08/28 06:00 MHDA- 2019/10/29 06:00 PMCR- 2019/08/27 CRDT- 2019/08/28 06:00 PHST- 2018/08/19 00:00 [received] PHST- 2019/08/06 00:00 [accepted] PHST- 2019/08/28 06:00 [pubmed] PHST- 2019/10/29 06:00 [medline] PHST- 2019/08/28 06:00 [entrez] PHST- 2019/08/27 00:00 [pmc-release] AID - 10.1007/s00262-019-02375-z [pii] AID - 2375 [pii] AID - 10.1007/s00262-019-02375-z [doi] PST - ppublish SO - Cancer Immunol Immunother. 2019 Sep;68(9):1467-1477. doi: 10.1007/s00262-019-02375-z. Epub 2019 Aug 27.