asco@alo33:161991 JSONTXT

Background: irAE occur as a result of autoimmunity triggered by ICI during cancer treatment. We hypothesize that more patients pts ill develop any grade irAE if treated ith ICI targeting immune and regulatory T-cells CTLA-4 than those treated ith ICI targeting immune cells ithout T regulatory PD-1 and those targeting non-immune cells having the least pts to develop irAE PD-L1 . Methods: We revieed all ICI cancer clinical trials 104; 201 arms that reported irAE and ere published on PubMed or presented at an ASCO meeting only if not published on PubMed during 2005-2015. 127 arms from 81 trials met the inclusion criteria for this meta-analysis. We collected and compared arm-specific data including ICI target, number of pts ith irAE any grade A , grade 3+ B and grade 5, specific irAE A and B, response rate, evaluable pts for irAE and for response. R package x201C;metax201D; as used for the meta-analysis to calculate and compare percent of pts ith irAE and response rates. Results: 116 91 percent arms used ICI monotherapy and 11 9 percent arms used combination of ICI to treat 11400 pts. 122 96 percent arms included solid tumors. 102 80 percent arms ere phase 12. See Table belo. Higher percent of pts ith irAE A as observed ith ICI CTLA-4 folloed by ICI PD-1 then ICI PD-L1 Plt0.0001 . ICI CTLA-4 had higher percent of pts ith irAE B than others; no significant difference in percent of pts ith irAE B as observed ith ICI PD-1 and PD-L1. Conclusions: Our meta-analysis supported our mechanistic-driven hypothesis that ICI targeting less immune cells caused less pts to develop any grade irAE. We encourage investigators to report percent pts ith irAE in ICI combination trials in order to balance their toxicity and efficacy profiles. ltth class=border-bottom align-left ICIArms that met inclusion criteriaEvaluable pts for irAEEvaluable pts for response percent pts ith irAE, any grade percent pts ith irAE, grade 3+ percent pts ith irAE grade 5Overall response rateCTLA-4564284316054 percent19 percent1.4 percent10.6 percentPD-1354074363626 percent3.8 percentx002A;0.8 percent27.5 percentPD-L125244849113.7 percent5 percentx002A;1.1 percent17.6 percentPD-1 + CTLA-484951242NR+NR1.8 percent47.8 percentPD-L1 + CTLA-439960NRNR1.8 percent28.6 percentTotal P127114008589P lt0.0001P lt0.0001P =0.34P lt0.0001ltfn id=TF-161991-001-1 ltp class=mtgabstract-table-fn x002A; p = 0.33+: not reportedlttable-rap-foot ,J Clin Oncol 34, 2016 suppl; abstr e14562 ,Publication Only Developmental Therapeutics and Translational Research Immunotherapy