1563P - Literature review of TPOR agonists for CIT

Abstract

Background: Chemotherapy-induced thrombocytopenia (CIT) can lead to dose delay/reduction. Currently there are no specific treatment recommendations beyond transfusion. We performed a systematic literature search on the use of thrombopoietin receptor (TPOR) agonists for CIT. Methods: We searched the Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, PubMed, EMBASE, clinicaltrials.gov, and Health Technology Assessments from 1995-2017 for studies of TPOR agonists [eg, romiplostim, eltrombopag, TPO, and megakaryocyte growth and development factor (MGDF)] for CIT. Each publication was independently reviewed by two people and data extracted into Excel. Results: We screened 892 titles/abstracts, assessed 52 articles, and abstracted data from 14 articles and 15 abstracts/posters from 1997-2016 (10 TPO, 7 MGDF, 8 romiplostim, and 4 eltrombopag), which included 18 randomized trials. TPOR agonist regimens varied widely. Common cancers included leukemia/lymphoma (n = 8 studies) and non-small cell lung cancer (n = 4), and common chemotherapies were platinum-based (n = 15) or included cytarabine (n = 5). Median or mean baseline platelet counts were 56 × 109/L-324 × 109/L in studies to treat CIT (N = 7) and 109 × 109/L-597 × 109/L in studies to prevent CIT (N = 22). The 16 placebo-controlled or crossover studies (MGDF n = 6 studies, TPO n = 5, romiplostim n = 3, eltrombopag n = 2) generally found that TPOR agonists increased platelet counts and reduced transfusions and dose delays/reductions (Table). Safety measures included thromboses (n = 19 studies) and bleeding (n = 8).Table1563P Study Design and Endpoints TPOR Agonist vs. Control (Range study incidences)CIT Prevention: Vs. Placebo/Observation or Crossover (n = 16 studies)TPOR Agonist (N = 625)Control (N = 428)Efficacy EndpointChemotherapy dose delay/reduction3% - 40%58% - 75%Grade 3-4 thrombocytopenia0% - 100%0% - 42%Platelet transfusions6% - 58%8% - 83%Safety EndpointThrombosis0% - 29%0% - 33%Bleeding0% - 100%0% - 50%CIT Treatment: Vs. rhIL-11 (n = 2 studies)TPOR Agonist (N = 63)Control (N = 71)Efficacy EndpointChemotherapy dose delay/reductionN/AN/AGrade 3-4 thrombocytopeniaGrade 3: 54% Grade 4: 14%Grade 3: 85% Grade 4: 41%Platelet transfusions11%30%Safety EndpointThrombosisN/AN/ABleedingN/AN/ACIT Treatment: Vs. PBO/Observation or Crossover (n = 2 studies)TPOR Agonist (N = 172)Control (N = 65)Efficacy EndpointChemotherapy dose delay/reductionN/AN/AGrade 3-4 thrombocytopeniaN/AN/APlatelet transfusionsN/AN/ASafety EndpointThrombosis5% - 13%7% - 21%Bleeding2% - 9%9% Open table in a new tab Conclusions: While TPOR agonists have not been approved for use in CIT, this literature review suggests that TPOR agonists may increase platelet counts and decrease chemotherapy dose delay/reduction. Further study with well-characterized bleeding and platelet thresholds is needed to explore the possible benefits of TPOR agonists for CIT compared with current care options (eg, transfusions, dose reduction). Legal entity responsible for the study: Amgen Inc. Funding: Amgen Inc. Disclosure: G.A. Soff: Research support from Amgen. J. Fryzek: Employee of EpidStat, which serves as a consultant with Amgen. M. Mullins: Consultant for EpidStat, which itself consults for Amgen. L.C. Bylsma: Employee of EpidStat, which consults for Amgen. J.K. Park: Amgen employee. All other authors have declared no conflicts of interest.