Two Randomized Controlled Trials of Romiplostim for Chemotherapy-Induced Thrombocytopenia in Patients with Solid Tumors

Background: Treatment for chemotherapy-induced thrombocytopenia (CIT) has generally been limited to modification of chemotherapy regimen (dose reduction, treatment delay, omission, and/or discontinuation of one or more agents) or platelet transfusions, which provide only transient benefit and can be associated with adverse events. With data from a phase 2 prospective study and retrospective studies of the thrombopoietin receptor agonist romiplostim, National Comprehensive Cancer Network® (NCCN®) guidelines now include consideration of romiplostim for treatment of CIT. Two pivotal phase 3 randomized controlled trials of romiplostim to treat CIT in patients with solid tumors are underway.

Trial design: Patients (≥18 years old) with platelet count ≤85×10⁹/L and CIT from a prior regimen who are slated to receive (trial 1) oxaliplatin-based chemotherapy for esophageal, gastric, pancreatic, or colorectal cancer (NCT03362177) or (trial 2) carboplatin-based chemotherapy for non-small cell lung, ovarian, or breast cancer (NCT03937154) will be stratified by baseline platelet count and tumor type (trial 1) or specific carboplatin regimen (trial 2). Patients will be randomized 2:1 to receive romiplostim or placebo, respectively. Weekly study drug will be initiated at 2 μg/kg subcutaneously and titrated by 1 μg/kg (maximum of ≤10 μg/kg) to a target platelet count of ≥100×10⁹/L. When a platelet count of ≥100×10⁹/L is achieved or at Week 4, if deemed appropriate by the investigator, chemotherapy will be initiated. Treatment with study drug will be stopped after 12 weeks if platelet count ≥100×10⁹/L (or a platelet count deemed safe to proceed with chemotherapy) is not achieved. For each trial, once 81 of the 162 anticipated patients have completed 3 chemotherapy cycles, an interim analysis will be conducted.

Endpoints: For both studies, there is the same primary endpoint, i.e., thrombocytopenia-induced dose modification (ie, dose reduction, delay, omission, and/or discontinuation) of any myelosuppressive agent in the second and third cycles of the planned chemotherapy regimen, as adjudicated by an independent committee (oncologists and a biostatistician). Secondary endpoints include safety, survival, platelet response (proportion achieving response, time to response), platelet nadir (depth), grade ≥2 bleeding rate (adjusted for duration), and incidence of platelet transfusion. Previously presented at ESMO 2022, FPN 1628TiP, Al-Samkari et al. Reused with permission.

Al-Samkari:argenx: Consultancy; Novartis: Consultancy; Sobi: Consultancy, Research Funding; Amgen: Research Funding; Forma: Consultancy; Rigel: Consultancy; Moderna: Consultancy; Agios: Consultancy, Research Funding; Dova: Consultancy, Research Funding. Geredeli:Bayer: Honoraria; Amgen: Honoraria; Roche: Honoraria; BMS: Honoraria; Pfizer: Honoraria; Takeda: Honoraria; Astellas: Honoraria; AstraZeneca: Honoraria; Merck: Honoraria; Eczacibasi: Honoraria; Novartis: Honoraria; Deva: Honoraria. 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Romiplostim is under investigation for use in chemotherapy-induced thrombocytopenia.