Romiplostim management of chemotherapy-induced thrombocytopenia

Background: Chemotherapy-induced thrombocytopenia (CIT) is a common toxicity of cancer therapy, often leading to delay or reduction in chemotherapy. We conducted a randomized open-label phase II clinical trial of Romiplostim versus Observation for CIT. Methods: Solid tumor patients with CIT ( < 100,000/mcL) for at least 4 weeks, requiring delay or reduction in dose of chemotherapy, were randomized 2:1 to weekly romiplostim or observation. Chemotherapy was held for at least 14 days prior to enrollment. Primary endpoint was correction of platelet ( > 100,000/mcL) within 3 weeks. Observation patients who failed to spontaneously correct platelet counts were eligible to cross over to receive romiplostim. Secondary endpoints included ability to tolerate resumption of chemotherapy for at least 2 cycles without recurrence of CIT. Results: 21 patients have been enrolled and reached the primary endpoint. 13 of the 14 (93%) romiplostim patients normalized their platelet count within the three-week primary endpoint period. The remaining romiplostim patient also normalized her platelet count, but beyond the primary endpoint. Of the 7 observation patients, only 1 (14%) spontaneously corrected her platelet count within 3 weeks. (P = 0.0009 by two-tailed Fisher's Exact Test). 5 Observation patients were crossed over to romiplostim for at least 3 weeks, and all reached 100,000/mcL. Including initial romiplostim as well as cross over treatment, 18 of 19 patients (95%) reached platelet counts of 100,000/mcL within 3 weeks of treatment. No patient who resumed chemotherapy while receiving romiplostim (N = 14) had a recurrence of CIT and no adverse events were attributed to romiplostim. Based on the highly significant efficacy, it was felt inappropriate to continue randomizing to observation and the study is being amended accordingly. Conclusions: Weekly administration of romiplostim improves platelet counts in cancer patients with dose-limiting CIT allowing resumption of full-dose chemotherapy. We do not yet know if correction of CIT, allowing on-time, full-dose chemotherapy, will result in improved clinical outcomes. A future clinical trial evaluating romiplostim intervention on Progression Free Survival for patients with CIT is planned to follow.