PMID- 29469949 OWN - NLM STAT- MEDLINE DCOM- 20190910 LR - 20201209 IS - 1097-0142 (Electronic) IS - 0008-543X (Print) IS - 0008-543X (Linking) VI - 124 IP - 9 DP - 2018 May 1 TI - Safety profile of avelumab in patients with advanced solid tumors: A pooled analysis of data from the phase 1 JAVELIN solid tumor and phase 2 JAVELIN Merkel 200 clinical trials. PG - 2010-2017 LID - 10.1002/cncr.31293 [doi] AB - BACKGROUND: Antibodies targeting the programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) checkpoint may cause adverse events (AEs) that are linked to the mechanism of action of this therapeutic class and unique from those observed with conventional chemotherapy. METHODS: Patients with advanced solid tumors who were enrolled in the phase 1 JAVELIN Solid Tumor (1650 patients) and phase 2 JAVELIN Merkel 200 (88 patients) trials received avelumab, a human anti-PD-L1 IgG1 antibody at a dose of 10 mg/kg every 2 weeks. Treatment-related AEs (TRAEs) were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0). In post hoc analyses, immune-related AEs (irAEs) were identified via an expanded AE list and medical review, and infusion-related reactions (IRRs) occurring /=3 TRAEs occurred in 177 (10.2%); the most common were fatigue (17 patients; 1.0%) and IRR (10 patients; 0.6%). TRAEs led to discontinuation in 107 patients (6.2%) and death in 4 patients (0.2%). Grade >/=3 irAEs occurred in 39 patients (2.2%) and led to discontinuation in 34 patients (2.0%). IRRs or related symptoms occurred in 439 patients (25.3%; grade 3 in 0.5% [9 patients] and grade 4 in 0.2% [3 patients]). An IRR occurred at the time of first infusion in 79.5% of 439 patients who had an IRR, within the first 4 doses in 98.6% of 439 patients who had an IRR, and led to discontinuation in 35 patients (2.0%). CONCLUSIONS: Avelumab generally was found to be well tolerated and to have a manageable safety profile. A minority of patients experienced grade >/=3 TRAEs or irAEs, and discontinuation was uncommon. IRRs occurred mainly at the time of first infusion, and repeated events were infrequent. Cancer 2018;124:2010-7. (c) 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. CI - (c) 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. FAU - Kelly, Karen AU - Kelly K AD - Department of Internal Medicine, University of California-Davis Comprehensive Cancer Center, Sacramento, California. FAU - Infante, Jeffrey R AU - Infante JR AD - Sarah Cannon Research Institute/Tennessee Oncology, PLLC, North Nashville, Tennessee. FAU - Taylor, Matthew H AU - Taylor MH AD - Oregon Health and Science University Knight Cancer Institute, Portland, Oregon. FAU - Patel, Manish R AU - Patel MR AD - Sarah Cannon Research Institute/Florida Cancer Specialists, Sarasota, Florida. FAU - Wong, Deborah J AU - Wong DJ AD - Department of Medicine, University of California at Los Angeles, Los Angeles, California. FAU - Iannotti, Nicholas AU - Iannotti N AD - Hematology Oncology Associates of the Treasure Coast, Port St. Lucie, Florida. FAU - Mehnert, Janice M AU - Mehnert JM AUID- ORCID: 0000-0002-1043-3008 AD - Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey. FAU - Loos, Anja H AU - Loos AH AD - Merck KGaA, Darmstadt, Germany. FAU - Koch, Helga AU - Koch H AD - Merck KGaA, Darmstadt, Germany. FAU - Speit, Isabell AU - Speit I AD - Merck KGaA, Darmstadt, Germany. FAU - Gulley, James L AU - Gulley JL AD - Genitourinary Malignancies Branch, Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180222 PL - United States TA - Cancer JT - Cancer JID - 0374236 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Antineoplastic Agents, Immunological) RN - 0 (B7-H1 Antigen) RN - 0 (CD274 protein, human) RN - KXG2PJ551I (avelumab) SB - IM MH - Aged MH - Antibodies, Monoclonal/administration & dosage/*adverse effects MH - Antibodies, Monoclonal, Humanized MH - Antineoplastic Agents, Immunological/administration & dosage/*adverse effects MH - B7-H1 Antigen/*antagonists & inhibitors/immunology MH - Clinical Trials, Phase I as Topic MH - Clinical Trials, Phase II as Topic MH - Disease Progression MH - Dose-Response Relationship, Drug MH - Fatigue/chemically induced/*epidemiology/immunology MH - Female MH - Follow-Up Studies MH - Humans MH - Incidence MH - Infusions, Intravenous/adverse effects MH - Injection Site Reaction/*epidemiology/immunology MH - Male MH - Middle Aged MH - Multicenter Studies as Topic MH - Neoplasms/*drug therapy/immunology/pathology MH - Treatment Outcome PMC - PMC5947549 OTO - NOTNLM OT - JAVELIN OT - avelumab OT - immunotherapy OT - programmed death-ligand 1 (PD-L1) OT - safety EDAT- 2018/02/23 06:00 MHDA- 2019/09/11 06:00 PMCR- 2018/05/11 CRDT- 2018/02/23 06:00 PHST- 2017/11/21 00:00 [received] PHST- 2018/01/17 00:00 [revised] PHST- 2018/01/23 00:00 [accepted] PHST- 2018/02/23 06:00 [pubmed] PHST- 2019/09/11 06:00 [medline] PHST- 2018/02/23 06:00 [entrez] PHST- 2018/05/11 00:00 [pmc-release] AID - CNCR31293 [pii] AID - 10.1002/cncr.31293 [doi] PST - ppublish SO - Cancer. 2018 May 1;124(9):2010-2017. doi: 10.1002/cncr.31293. Epub 2018 Feb 22.