Findings of representative studies (including 20 or more patients) of thrombopoietin receptor agonists for the treatment of CIT in adults
| Study . | Patient population . | Chemotherapy regimen . | Principal findings . |
|---|---|---|---|
| Romiplostim | |||
| Parameswaran et al27 (CIT treatment) | 20 patients with various solid tumors who developed CIT (platelets <100 × 109/L for ≥6 weeks) Observational cohort | Various regimens | 95% of patients achieved platelets >100 × 109/L 75% resumed cytotoxic chemotherapy and all but 1 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 and Kuter26 (CIT treatment) | 22 patients with various solid tumors who developed CIT (as defined by treating physician) Observational cohort | Various regimens | 95% of patients achieved platelets >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 et al4 (CIT treatment) | 60 patients with various solid tumors who developed persistent CIT (platelets <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 platelets >100 × 109/L compared with 12.5% untreated observation Only 7% of patients of patients who achieved platelets >100 × 109/L experienced recurrent chemotherapy dose reduction or treatment delay 10.2% of patients had VTE over 12 months; bleeding not reported |
| Al-Samkari et al5 (CIT treatment) | 173 patients with various malignancies (153 solid tumor, 20 lymphoma/myeloma) who developed persistent CIT (platelets <100 × 109/L for ≥3 weeks or chemotherapy delay of ≥1 week due to thrombocytopenia) Observational cohort | Various regimens | 85% achieved platelets >100 × 109/L (95% without predictors of nonresponse) 71% achieved platelets >75 × 109/L and ≥30 × 109/L higher than pretreatment baseline (82% without predictors of nonresponse) 79% avoided chemotherapy dose reduction or treatment delay; 89% avoided platelet transfusion Bone marrow tumor invasion, prior pelvic irradiation, and prior temozolomide predicted romiplostim nonresponse VTE rate 14 per 100 patient-years; bleeding rate 23 per 100 patient-years (1% of 1063 cycles supported with romiplostim) |
| Eltrombopag | |||
| Kellum et al29 (CIT prevention) | 183 chemotherapy-naive 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 end point (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 et al31 (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 et al30 (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 et al5 (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 end point (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 the placebo arm during the interventional chemotherapy cycle Avatrombopag-treated patients had higher platelet counts Avatrombopag overall safe and well tolerated in patients with cancer with a safety profile similar to placebo Venous thromboembolism rate 2.4% in avatrombopag arm vs 2.5% in placebo arm |
| Study . | Patient population . | Chemotherapy regimen . | Principal findings . |
|---|---|---|---|
| Romiplostim | |||
| Parameswaran et al27 (CIT treatment) | 20 patients with various solid tumors who developed CIT (platelets <100 × 109/L for ≥6 weeks) Observational cohort | Various regimens | 95% of patients achieved platelets >100 × 109/L 75% resumed cytotoxic chemotherapy and all but 1 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 and Kuter26 (CIT treatment) | 22 patients with various solid tumors who developed CIT (as defined by treating physician) Observational cohort | Various regimens | 95% of patients achieved platelets >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 et al4 (CIT treatment) | 60 patients with various solid tumors who developed persistent CIT (platelets <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 platelets >100 × 109/L compared with 12.5% untreated observation Only 7% of patients of patients who achieved platelets >100 × 109/L experienced recurrent chemotherapy dose reduction or treatment delay 10.2% of patients had VTE over 12 months; bleeding not reported |
| Al-Samkari et al5 (CIT treatment) | 173 patients with various malignancies (153 solid tumor, 20 lymphoma/myeloma) who developed persistent CIT (platelets <100 × 109/L for ≥3 weeks or chemotherapy delay of ≥1 week due to thrombocytopenia) Observational cohort | Various regimens | 85% achieved platelets >100 × 109/L (95% without predictors of nonresponse) 71% achieved platelets >75 × 109/L and ≥30 × 109/L higher than pretreatment baseline (82% without predictors of nonresponse) 79% avoided chemotherapy dose reduction or treatment delay; 89% avoided platelet transfusion Bone marrow tumor invasion, prior pelvic irradiation, and prior temozolomide predicted romiplostim nonresponse VTE rate 14 per 100 patient-years; bleeding rate 23 per 100 patient-years (1% of 1063 cycles supported with romiplostim) |
| Eltrombopag | |||
| Kellum et al29 (CIT prevention) | 183 chemotherapy-naive 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 end point (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 et al31 (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 et al30 (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 et al5 (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 end point (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 the placebo arm during the interventional chemotherapy cycle Avatrombopag-treated patients had higher platelet counts Avatrombopag overall safe and well tolerated in patients with cancer with a safety profile similar to placebo Venous thromboembolism rate 2.4% in avatrombopag arm vs 2.5% in placebo arm |