16 November 2020: Articles
Avatrombopag Optimizes Response to Niraparib by Managing Thrombocytopenia Associated with Poly-ADP Ribose Polymerase (PARP) Inhibition in Ovarian Cancer and Breast Cancer: A Case Series
Unusual or unexpected effect of treatment
Nash Gabrail A* , Carrie Smith ADOI: 10.12659/AJCR.927008
Am J Case Rep 2020; 21:e927008
Table 1. Outcomes in patients receiving avatrombopag to optimize therapeutic outcomes with niraparib therapy in breast cancer and ovarian cancer.
| Therapeutic doses used* | Sustained maximal dose of niraparib** (Y/N) | Biomarkers confirming clinical response | Key notes on case | |
|---|---|---|---|---|
| Case 1 (breast cancer with brain metastases) | Avatrombopag: 0–140 mg/weekNiraparib: 0–2100 mg/week | Y | CT-confirmed intracranial response and successful discontinuation of steroids and absence of reported seizures after intracranial response enabled by niraparib and avatrombopag | Use of niraparib in this patient initially led to profound thrombocytopenia (31,000/µL), which was rapidly transformed to a supranormal platelet count (757,000/µL) when the patient received avatrombopag 20 mg daily. Dosing of avatrombopag 20 mg two to three times weekly (total weekly dose: 40 mg to 60 mg) enabled continued therapy with niraparib and clinical response |
| Case 2 (breast cancer with brain metastases) | Avatrombopag: 140–280 mg/weekNiraparib: 0–2100 mg/week | N | CT-confirmed intracranial partial response confirmed on 2 occasions | Continuous administration of avatrombopag for all but 3 weeks enabled titration to the maximal dose of niraparib, enabling intracranial partial response. Of note, a period when avatrombopag was interrupted led to a reduction in platelet counts in subsequent months |
| Case 3 (ovarian cancer) | Avatrombopag: 140 mg/weekNiraparib: 0–2100 mg/week | Y | Reduction in CA-125 levels in association with treatment with niraparib enabled by avatrombopag therapy | The patient has been able to receive the maximal dose of niraparib while receiving avatrombopag. Notably, the maximal dose of niraparib caused profound thrombocytopenia (36,000/µL) when it was administered without avatrombopag. CA-125 levels increased upon niraparib dose interruption and increased upon niraparib dose escalation enabled by avatrombopag therapy |
| Case 4 (ovarian cancer) | Avatrombopag: 140–280 mg/weekNiraparib: 0–2100 mg/week | Y | CA-125 levels were stable during continued dosing of niraparib and avatrombopag | Use of avatrombopag enabled the patient to tolerate a maximal dose of niraparib. CA-125 levels were stable during continued dosing of niraparib and avatrombopag |
| Case 5 (ovarian cancer) | Avatrombopag: 140–280 mg/weekNiraparib: 0–2100 mg/week | N | Drop in CA-125 levels in association with continued dosing of niraparib and avatrombopag | Use of avatrombopag enabled the patient to tolerate a weekly dose of 500 mg of niraparib, which was later escalated to 1000 mg of niraparib. A reduction in CA-125 levels was observed with niraparib dose optimization |
| Case 6 (ovarian cancer) | Avatrombopag: 0–280 mg/weekNiraparib: 0–2100 mg/week | N | CA-125 levels were stable during continued dosing of niraparib and avatrombopag. The patient experienced complete response and is disease-free as of March 2020 | While receiving concurrent avatrombopag, the patient was able to maintain platelet counts above 100,000/µL while on niraparib with some niraparib dose reductions. Avatrombopag therapy enabled this patient to tolerate niraparib, which may not have been possible in the absence of avatrombopag |
| * Total weekly dose of treatments administered daily; ** defined as 3 or more consecutive weeks receiving niraparib 300 mg daily. | ||||