Niraparib was the first PARPi to demonstrate significant improvement in progression-free survival (PFS) in patients with relapsed platinum-sensitive ovarian cancer regardless of BRCA mutation status in a randomized, placebo-controlled phase III trial (ENGOT-OV16\/NOVA) [6]. For example, PFS in patients with BRCA germline mutation (gBRCA) was prolonged by 15.5 months (niraparib: 21.0 months; placebo: 5.5 months; HR 0.27; P<0.001) and in patients without BRCA germline mutation (non-gBRCA) by 5.4 months (niraparib: 9.3 months; placebo: 3.9 months; HR 0.45; P<0.001) [6].<\/p>\n
Based on these study results, niraparib has been approved in Switzerland since October 2018 as maintenance therapy in patients with platinum-sensitive, recurrent, primary epithelial serous high-grade ovarian, tubal, or peritoneal carcinoma after complete or partial response to platinum-based chemotherapy [4].<\/p>\n
The other PARPi approved in Switzerland, olaparib, also showed positive results in terms of PFS in the randomized, placebo-controlled phase III SOLO2\/ENGOT-Ov21 trial, but only in patients with gBRCA [7]. For non-gBRCA, data are available from the phase II study 19 and the single-arm phase IIIb OPINION study [8, 9].<\/p>\n
Reduced starting dose enables same efficacy with fewer side effects<\/strong><\/p>\n Good tolerability and preservation of health-related quality of life, in addition to efficacy, are central concerns of maintenance therapies [10]. In general, the side effects of niraparib therapy were well managed [6]. The most common serious adverse events (grade 3\/4) with niraparib included thrombocytopenia (33.8%), anemia (25.3%), and neutropenia (19.6%) and occurred mostly in the first three cycles of treatment [6]. In contrast, after individual dose adjustments, thrombocytopenia, neutropenia, and fatigue (grade 3\/4) were less frequent in later cycles [6]. Thrombocytopenias were mostly transient and platelet counts stabilized from the third cycle of treatment [6].<\/p>\n A retrospective analysis of ENGOT-OV16\/NOVA data examined the associations between niraparib dose and the occurrence of treatment-associated adverse events (TEAEs) [5]. This showed that dose reductions were made in 68.9% of patients due to TEAEs, mostly within the first three months of treatment. The most common of these was a reduction in the dose of niraparib from 300 mg to 200 mg, which increased the rate of 3rd\/4th TEAEs. degree decreased significantly. A lower rate of anemia (grade 3\/4) was observed only at a niraparib dose of 100 mg [5]. In addition, a low platelet count (<150000\/\u00b5l) and a body weight <77 kg were identified as risk factors for the development of grade 3\/4 thrombocytopenia within the first 30 days on niraparib [5]. No difference in efficacy was observed in patients receiving a reduced dose of niraparib (200 mg or 100 mg) compared with the higher dose of 300 mg. To exclude a bias against the 300 mg dose, PFS data were only considered from the fourth month of treatment onwards, as most patients had reached a stable dose by then [5].<\/p>\n Based on these results, niraparib was approved in Switzerland with a recommended starting dose of 200 mg [4]. Only in patients with a body weight Good compatibility in real-world settings<\/strong><\/p>\n Treatment with 200 mg niraparib is also associated with improved tolerability under real-world conditions [2]. This is according to a real-world study that evaluated anonymized dossiers from 153 patients who received niraparib at a starting dose of 200 mg [2]. Patients were median 59 years old and weighed median 70 kg. The median time between completion of platinum-based chemotherapy and initiation of maintenance therapy with 200 mg niraparib was 33 days [2]. In clinical trials, nausea, thrombocytopenia, and fatigue were the most common adverse events with niraparib. In the real-world setting, these adverse events occurred in 37% of patients within the first three months, but showed a significantly reduced incidence with 200 mg niraparib compared with the starting dose of 300 mg niraparib in the ENGOT-OV16\/NOVA trial (Figure 1). A reduction in niraparib dose from 200 mg to 100 mg occurred in 11% of patients. Interruption of therapy due to side effects was necessary in 4% of patients and in only 2% did treatment have to be discontinued within the first three months [2].<\/p>\n Figure 1:<\/strong> Incidence of the three most common grade 3\/4 adverse events in patients in the real-world clinical setting (niraparib starting dose 200 mg) compared with patients in the ENGOT-OV16\/NOVA trial (niraparib starting dose 300 mg), modified from [2].<\/p>\n Conclusion<\/strong><\/p>\n Switzerland is the first country to approve niraparib with a reduced starting dose of 200 mg [4]. This dose reduction can significantly reduce the rate of side effects compared with 300 mg dosing without compromising the efficacy of maintenance therapy [5, 6]. As shown in a real-world study, the reduced dose is also associated with improved tolerability in clinical practice [2]. Individual dose adjustments allow optimal management of side effects, thus helping to preserve patients’ quality of life during maintenance therapy [2].<\/p>\n
\n\u2265 77 kg and a normal platelet count (\u2265150,000\/\u00b5l), niraparib therapy continues to be initiated at a dose of 300 mg [4]. Niraparib only needs to be taken once daily, which simplifies therapy and thus supports adherence [4].<\/p>\n![\"\"](\"https:\/\/assets.medizinonline.com\/sites\/default\/files\/field\/images\/abb1_2.png\")
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