Table 2.
Findings of representative studies (including 20 or more patients) of thrombopoietin receptor agonists for the treatment of CIT in adults. Adapted with permission from Al-Samkari 2022 [8].
| Study | Patient Population | Chemotherapy Regimen | Principal Findings |
|---|---|---|---|
| Romiplostim | |||
| Parameswaran 2014[52] CIT Treatment |
20 patients with various solid tumors who developed CIT (Plt <100×109/L for ≥6 weeks) Observational cohort |
Various regimens | 95% of patients achieved Plt >100×109/L 75% resumed cytotoxic chemotherapy and all but one of these patients tolerated at least 2 additional chemotherapy cycles on romiplostim support without recurrence of dose-limiting CIT 3 patients developed VTE; bleeding not reported |
| Al-Samkari 2018[18] CIT Treatment |
22 patients with various solid tumors who developed CIT (as defined by treating physician) Observational cohort |
Various regimens | 95% of patients achieved Plt >100×109/L 100% resumed cytotoxic chemotherapy, receiving 2 or more cycles (range, 2–18) on romiplostim Significant reduction in dose reductions and treatment delays on romiplostim, with some patients able to dose-escalate No patients developed VTE; 3 developed bleeding |
| Soff 2019[19] CIT Treatment |
60 patients with various solid tumors who developed persistent CIT (Plt <100×109/L for ≥4 weeks without chemotherapy treatment) randomized to romiplostim or untreated observation; ultimately 52 received romiplostim Randomized phase 2 trial |
Various regimens | 85% of patients treated with romiplostim achieved Plt >100×109/L compared to 12.5% untreated observation Only 7% of patients of patients who achieved Plt >100×109/L experienced recurrent chemotherapy dose-reduction or treatment delay 10.2% of patients had VTE over 12 months; bleeding not reported Subsequent publication [53] confirmed similar safety and efficacy with extended duration use in the study population |
| Al-Samkari 2021[16] CIT Treatment |
173 patients with various malignancies (153 solid tumor, 20 lymphoma/myeloma) who developed persistent CIT (Plt <100×109/L for ≥3 weeks or chemotherapy delay of ≥1 week due to thrombocytopenia) Observational cohort |
Various regimens | 85% achieved Plt >100×109/L (95% without predictors of non-response) 71% achieved Plt >75×109/L and ≥30×109/L higher than pretreatment baseline (82% without predictors of non-response) 79% avoided chemotherapy dose-reduction or treatment delay; 89% avoided platelet transfusion Bone marrow tumor invasion, prior pelvic irradiation, prior temozolomide predicted romiplostim non-response VTE rate 14 per 100 patient-years; bleeding rate 23 per 100 patient-years (1% of 1063 cycles supported with romiplostim) |
| Eltrombopag | |||
| Kellum 2010[74] CIT Prevention |
183 chemotherapy-naïve patients with various advanced solid tumors randomized to placebo or eltrombopag 50, 75, or 100 mg; 134 patients completed at least 2 cycles and could be evaluated Randomized phase 2 trial |
Carboplatin and paclitaxel | Primary endpoint (significant difference in the change in platelet count from day 1 in cycle 2 to the platelet nadir in cycle 2 between eltrombopag and placebo-treated patients) not met Eltrombopag-treated patients had higher platelet counts at start of subsequent treatment cycles (higher counts with higher eltrombopag dose) |
| Winer 2015[75] CIT Prevention |
26 patients with pancreatic cancer randomized to receive eltrombopag 100 mg or placebo Randomized phase 1 trial |
Gemcitabine or gemcitabine plus cisplatin or carboplatin | Mean platelet nadirs significantly higher in eltrombopag-treated patients Chemotherapy dose reduction or treatment delay occurred in 50% of placebo-treated patients vs. 14% of eltrombopag-treated patients |
| Winer 2017[76] CIT Prevention |
75 patients with various solid tumors randomized to receive eltrombopag 100 mg or placebo; only 26 of the enrolled patients completed the planned number of cycles Randomized phase 2 trial |
Gemcitabine or gemcitabine plus cisplatin or carboplatin | Eltrombopag-treated patients had higher platelet counts, lower frequencies of grade 3 or 4 CIT, more rapid platelet count recovery, and fewer dose reductions/treatment delays or missed doses due to thrombocytopenia Rates of grade 3 or 4 CIT remained high overall in both arms |
| Avatrombopag | |||
| Al-Samkari 2022[16] CIT Treatment |
122 patients with lung, ovarian, or bladder cancer with primarily nadir CIT randomized to receive avatrombopag 40 mg daily or placebo for 1 chemotherapy cycle Randomized phase 3 trial |
Various regimens | Similar proportions of patients achieved the primary endpoint (of avoidance of chemotherapy treatment delay, dose reduction, bleeding, or platelet transfusion) in avatrombopag (70%) and placebo (73%) groups, due to high rates of unexpected higher platelet count nadirs in placebo arm during the interventional chemotherapy cycle Avatrombopag-treated patients had higher platelet counts Avatrombopag overall safe and well-tolerated in cancer patients with a safety profile similar to placebo Arterial thromboembolism rate 2.4% in avatrombopag arm versus 2.5% in placebo arm No venous thromboembolic events in either arm |