Comparative Efficacy and Safety of PARP Inhibitors as Maintenance Therapy in Platinum Sensitive Recurrent Ovarian Cancer: A Network Meta-Analysis

This meta-analysis investigated the comparative efficacy and safety of PARP inhibitor monotherapy as maintenance treatment in platinum sensitive recurrent ovarian cancer (ROC). Electronic databases were systematically searched for relevant RCTs. The primary endpoint was PFS. The results were stratified based on three categories: BRCA mutated patients, HRD patients, and overall population. The secondary outcome were discontinuations due to adverse events and grade 3 or 4 adverse events in maintenance phase. Five eligible RCTs were included in the network meta-analysis. For patients with BRCA mutated ovarian cancer, olaparib-throughout (HR = 0.21 with 95% CrI: 0.081–0.55), rucaparib (HR = 0.23 with 95% CrI: 0.16–0.34), olaparib (HR = 0.27 with 95% CrI: 0.20–0.35), and niraparib (HR = 0.26 with 95% CrI: 0.17–0.41) were all highly effective in comparison with placebo at improving PFS. For HRD patients, both rucaparib (HR = 0.32 with 95% CrI: 0.24–0.42) and niraparib (HR = 0.38 with 95% CrI: 0.24–0.60) were all highly effective in comparison with placebo at improving PFS. For the overall population, olaparib-throughout (HR = 0.51 with 95% CrI: 0.34–0.76), rucaparib (HR = 0.37 with 95% CrI: 0.30–0.45), olaparib (HR = 0.35 with 95% CrI: 0.25–0.49), and niraparib (HR = 0.38 with 95% CrI: 0.30–0.48) were all highly effective in comparison with placebo at improving PFS. Regarding grade 3 or 4 adverse events, the incidence of grade 3 or 4 toxicity reactions to rucaparib and niraparib were significantly higher than in the olaparib group. In terms of discontinuations due to adverse events, the treatment discontinuations were not significantly different between the three drugs. In summary, all the included maintenance treatment regimens are effective regardless of BRCA mutational status, and no statistically significant differences between rucaparib, niraparib and Olaparib in terms of PFS. In terms of safety profile, the three drugs present manageable adverse events. Clinicians should consider potential adverse events related to each of these interventions in clinical practice, and the adverse events are generally manageable.

Download Full-text

Comparison of the Efficacy and Safety of PARP Inhibitors as a Monotherapy for Platinum-Sensitive Recurrent Ovarian Cancer: A Network Meta-Analysis

Frontiers in Oncology ◽

10.3389/fonc.2021.785102 ◽

2021 ◽

Vol 11 ◽

Author(s):

Hongmei Wang ◽

Meng Wu ◽

Haonan Liu ◽

Hang Zhou ◽

Yang Zhao ◽

...

Keyword(s):

Ovarian Cancer ◽

Maintenance Treatment ◽

Brca Mutation ◽

Meta Analysis ◽

Recurrent Ovarian Cancer ◽

Home Treatment ◽

Efficacy And Safety ◽

Risk Of Death ◽

Platinum Sensitive ◽

Grade 3

BackgroundThe present COVID-19 pandemic has tended toward normality. To provide convenient, safe, and effective home treatment programs for patients with recurrent ovarian cancer (ROC), the clinical efficacy and safety of poly (ADP-ribose) polymerase inhibitor (PARPi) (including olaparib, niraparib, and rucaparib) monotherapy as a maintenance treatment for platinum-sensitive ROC were systematically evaluated.MethodsNumerous electronic databases were systematically searched for randomized controlled trials (RCTs) of PARPi maintenance treatment for ROC that were published before June 2021. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoint was grade 3-4 adverse effects (AEs). After data extraction and the quality evaluation of the included studies, Bayesian network meta-analysis (NMA) was performed using R software. The ability of each treatment was ranked using the surface under the cumulative ranking (SUCRA) curve.ResultsThe analysis included five studies and 1390 patients. The NMA results demonstrated that compared with the placebo, olaparib and niraparib exhibited significant benefits in the gBRCA-mutated population, and respectively reduced the risk of death by 31% (HR = 0.69, 95% CI: 0.53-0.90) and 34% (HR = 0.66, 95% CI: 0.44-0.99). Olaparib, niraparib, and rucaparib were all found to be very effective in prolonging PFS in patients with ROC. All three PARPi treatments increased the number of grade 3-4 AEs in patients with ROC as compared with the placebo.ConclusionsOverall, olaparib and niraparib maintenance treatment can significantly prolong the OS of patients with gBRCA mutations. Furthermore, the three investigated PARPi monotherapy maintenance treatments can prolong PFS regardless of BRCA mutation status. Although the incidence of AEs in the treatment groups was found to be significantly higher than that in the placebo group, the patients in the treatment group tolerated the treatment. Home oral PARPi treatment can balance tumor treatment and pandemic prevention and control, and is the most convenient, safe, and effective home treatment method available against the background of the current COVID-19 pandemic. Systematic Review Registrationhttps://inplasy.com/inplasy-2021-6-0033/.

Download Full-text

Real-life data of niraparib maintenance treatment in patients with recurrent platinum-sensitive ovarian cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.5560 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 5560-5560

Author(s):

Bente Vilming ◽

Jørgen Fallås-Dahl ◽

Anne-Gry Bentzen ◽

Vibeke Anett Ingebrigtsen ◽

Elisabeth Berge Nilsen ◽

...

Keyword(s):

Adverse Events ◽

Maintenance Treatment ◽

Real Life ◽

Phase Iii ◽

Efficacy And Safety ◽

Life Data ◽

Platinum Sensitive ◽

Real Life Data ◽

Individualized Dosing ◽

Grade 3

5560 Background: PARP (poly adenosine diphosphate [ADP]–ribose polymerase) inhibitors are the new standard for maintenance treatment in platinum sensitive recurrent ovarian cancer (PSROC), independent of germline (g-BRCA) or somatic BRCA mutation status. Real-life data after the introduction of new anti-neoplastic agents are needed to evaluate whether the benefit observed in phase III trials can be translated into clinical practice. The aim of this study was to provide real-life data on efficacy and safety of niraparib in non-gBRCA PSROC. Methods: This retrospective multi-center cohort study included patients with PSROC who were enrolled in a national individual patient access program in Norway. Efficacy and safety data were collected from the patients´ electronic medical records. The primary outcome was time from start of niraparib treatment to first subsequent treatment (TFST). Secondary endpoints included prevalence of dose interruption and -reduction, as well as adverse events. Results: The study included 106 patients with median age of 64 years (range 38-81). After median follow up of 15.3 months (95% CI 12.1-18.5), 71 patients (67%) had progressed, 64 (60%) had started a new line of treatment, and 25 (24%) had died. 25 (24%) patients were still receiving niraparib. Median duration of niraparib treatment was 7.6 months (0.4 to 27.3 months). Median TFST was 11.7 months (95% CI 9.2 -14.2). Patients with elevated CA125 after chemotherapy prior to start of niraparib had shorter progression-free survival (PFS) compared to patients with complete serological response (6.5 months (95% CI 5.7 – 7.3) vs 12 months (95% CI 6.2 – 17.9, (p < 0.001)). Grade 3-4 hematologic and non-hematologic events occurred in 25% and 17% of the patients, respectively. The most common grade 3/4 hematologic events were anemia (15%), thrombocytopenia (11%) and neutropenia (8%). Adverse events led to dose interruption in 38% and dose reduction in 44% of the patients. Patients with individualized dosing based on baseline weight and platelet counts had fewer dose reductions (p < 0.001) and -interruptions (p = 0.042) than patients whose dose was not adjusted to those baseline values. Conclusions: In a real-life setting, niraparib maintenance treatment in patients with non-gBRCA PSROC showed efficacy comparable with the published phase III data and an acceptable safety profile. Individualized dosing at start of treatment minimized adverse events. The prolonged PFS in patients with CA125 normalization after last chemotherapy, suggests that these patients in particular benefit from maintenance treatment but warrants confirmation in a larger sample.[Table: see text]

Download Full-text