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Laura J. Havrilesky - One of the best experts on this subject based on the ideXlab platform.
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Patient preference-weighted assessments using the ASCO value framework in recurrent, Platinum-Sensitive Ovarian Cancer.
Journal of Clinical Oncology, 2016Co-Authors: Jonathan Foote, Angeles Alvarez Secord, M.i. Liang, David E. Cohn, Laura J. HavrileskyAbstract:6630Background: The ASCO value framework allows comparisons of Cancer treatments based on Net Health Benefit (NHB) and cost. We aimed to assess the value of treatments for recurrent, platinum-sensi...
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Cost-effectiveness of combination versus sequential docetaxel and carboplatin for the treatment of Platinum-Sensitive, recurrent Ovarian Cancer.
Cancer, 2011Co-Authors: Laura J. Havrilesky, Robert V. Higgins, Lawrence R. Nycum, Matthew F. Kohler, Andrew Berchuck, Evan R. Myers, Robin Pokrzywinski, Dennis A. Revicki, Angeles Alvarez SecordAbstract:In a randomized controlled trial (RCT) of patients with recurrent, Platinum-Sensitive Ovarian Cancer, the combination weekly docetaxel and carboplatin was associated a with progression-free survival (PFS) of 13.7 months compared with 8.4 months for sequential, single-agent docetaxel followed by carboplatin. The objective of the current study was to construct a cost-utility model to compare these 2 regimens with the incorporation of prospectively collected quality-of-life (QoL) data. An RCT of concurrent docetaxel and carboplatin (cDC) versus docetaxel followed by carboplatin (sequential docetaxel and carboplatin [sDC]) was the basis for a Markov decision model, and the primary effectiveness outcome was PFS. Costs were estimated using US dollars based on Medicare reimbursements for chemotherapy regimens, bone marrow support, and management of adverse events. QoL data obtained using the Functional Assessment of Cancer Therapy-General questionnaire were converted to utilities. Costs and incremental cost-effectiveness ratios (ICERs) were reported in US dollars per quality-adjusted life year (QALY). Extensive 1-way sensitivity analyses and a Monte Carlo probabilistic sensitivity analysis were performed. The least expensive strategy was sDC, which cost an average of $20,381, compared with cDC, which cost an average of $25,122. cDC had an ICER of $25,239 per QALY compared with sDC. cDC remained cost-effective, with an ICER <$50,000 per QALY, over a range of costs and estimates. In Monte Carlo sensitivity analysis using a $50,000 per QALY willingness-to-pay threshold, cDC was either dominant or cost-effective with an ICER <$50,000 per QALY in 83% of simulations. Combined weekly cDC appeared to be cost-effective compared with sDC as treatment strategy for patients with Platinum-Sensitive Ovarian Cancer, even when accounting for slightly lower QoL during treatment. Copyright © 2011 American Cancer Society.
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Management of Platinum-Sensitive recurrent Ovarian Cancer: A cost-effectiveness analysis
Gynecologic oncology, 2007Co-Authors: Laura J. Havrilesky, Angeles Alvarez Secord, Shalini L Kulasingam, Evan R. MyersAbstract:We wished to compare the cost-effectiveness of three chemotherapy regimens for treatment of recurrent Platinum-Sensitive Ovarian Cancer. A Markov decision tree was constructed comparing three chemotherapy regimens: (1) carboplatin alone (C); (2) paclitaxel/carboplatin (PC); (3) gemcitabine/carboplatin (GC). Progression-free survival (PFS) and adverse event rates were estimated from published randomized controlled trials (RCTs). Costs of treatment and adverse events were obtained using Medicare reimbursement data. Estimated mean and median progression-free survival were 8.0 and 6.0 months for C, 10.1 and 7.8 months for PC, 10.5 and 8.4 months for GC, respectively. C was the least expensive strategy, costing $501 per progression-free month (PFM). PC had an incremental cost-effectiveness ratio (ICER) of $1297 per additional PFM ($15,564 per additional progression-free year (PFY)) compared to C. GC had an ICER of $23,199 per additional PFM ($278,388 per additional PFY) compared to PC. Results were insensitive to variation in the rates and costs of toxicities over clinically reasonable ranges. The model was sensitive to changes in PFS estimates. When the PFS of GC was assumed to be equivalent to that of PC, GC was strongly dominated (more expensive and no more effective) by PC due to the additional costs. Adjustment for neurotoxicity-associated quality of life (QoL) did not change rankings of strategies. PC appears to be relatively cost-effective compared to C for the treatment of recurrent Platinum-Sensitive Ovarian Cancer. GC appears to be less cost-effective compared to PC, with an ICER ten times higher.
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A comparison of combination docetaxel/carboplatin versus sequential docetaxel then carboplatin in patients with recurrent Platinum-Sensitive Ovarian Cancer
Journal of Clinical Oncology, 2006Co-Authors: Angeles Alvarez Secord, Laura J. Havrilesky, Robert V. Higgins, Lawrence R. Nycum, Matthew F. Kohler, L. E. Puls, Robert W. Holloway, John T. Soper, Fidel A. Valea, Andrew BerchuckAbstract:5092 Background: Combination paclitaxel and platinum-based chemotherapy has been shown to improve survival in patients with recurrent Platinum-Sensitive Ovarian Cancer. However, the incidence of ne...
Nicoletta Colombo - One of the best experts on this subject based on the ideXlab platform.
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Experience with trabectedin + pegylated liposomal doxorubicin for recurrent Platinum-Sensitive Ovarian Cancer unsuited to platinum rechallenge.
Expert review of anticancer therapy, 2016Co-Authors: Nicoletta Colombo, Gabriella Ferrandina, Anne Claire Hardy-bessard, Christian Marth, Ignacio RomeroAbstract:ABSTRACTIntroduction: As most patients with Ovarian Cancer experience multiple remissions and relapses, oncologists must prepare ahead for long-term treatment. While platinum-based regimens are standard of care for Platinum-Sensitive recurrence, there are circumstances in which platinum rechallenge is not the best approach. These situations include patients with limited sensitivity to platinum; patients with residual toxicity from previous platinum therapy; and patients at risk of developing hypersensitivity reactions. An alternative regimen for these patients is the non-platinum combination of trabectedin + pegylated liposomal doxorubicin (PLD).Areas covered: In this review, case studies are presented to illustrate how careful strategic planning, in terms of therapeutic choices and optimal sequencing, can achieve good outcomes in difficult-to-treat patients.Expert commentary: Advantages with use of trabectedin + PLD in selected patients with Platinum-Sensitive recurrent Ovarian Cancer include additional ...
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Olaparib combined with chemotherapy for recurrent Platinum-Sensitive Ovarian Cancer: a randomised phase 2 trial
The Lancet. Oncology, 2014Co-Authors: Amit M. Oza, Nicoletta Colombo, Christopher J. Poole, David Cibula, Ana Oaknin Benzaquen, Ron H.j. Mathijssen, Gabe S. Sonke, Jiří Špaček, Peter Vuylsteke, H HirteAbstract:The poly(ADP-ribose) polymerase inhibitor olaparib has shown antitumour activity in patients with Platinum-Sensitive, recurrent, high-grade serous Ovarian Cancer with or without BRCA1 or BRCA2 mutations. The aim of this study was to assess the efficacy and tolerability of olaparib in combination with chemotherapy, followed by olaparib maintenance monotherapy, versus chemotherapy alone in patients with Platinum-Sensitive, recurrent, high-grade serous Ovarian Cancer. In this randomised, open-label, phase 2 study, adult patients with Platinum-Sensitive, recurrent, high-grade serous Ovarian Cancer who had received up to three previous courses of platinum-based chemotherapy and who were progression free for at least 6 months before randomisation received either olaparib (200 mg capsules twice daily, administered orally on days 1-10 of each 21-day cycle) plus paclitaxel (175 mg/m(2), administered intravenously on day 1) and carboplatin (area under the curve [AUC] 4 mg/mL per min, according to the Calvert formula, administered intravenously on day 1), then olaparib monotherapy (400 mg capsules twice daily, given continuously) until progression (the olaparib plus chemotherapy group), or paclitaxel (175 mg/m(2) on day 1) and carboplatin (AUC 6 mg/mL per min on day 1) then no further treatment (the chemotherapy alone group). Randomisation was done by an interactive voice response system, stratified by number of previous platinum-containing regimens received and time to disease progression after the previous platinum regimen. The primary endpoint was progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1, analysed by intention to treat. Prespecified exploratory analyses included efficacy by BRCA mutation status, assessed retrospectively. This study is registered with ClinicalTrials.gov, number NCT01081951, and has been completed. Between Feb 12 and July 30, 2010, 173 patients at 43 investigational sites in 12 countries were enrolled into the study, of whom 162 were eligible and were randomly assigned to the two treatment groups (81 to the olaparib plus chemotherapy group and 81 to the chemotherapy alone group). Of these randomised patients, 156 were treated in the combination phase (81 in the olaparib plus chemotherapy group and 75 in the chemotherapy alone group) and 121 continued to the maintenance or no further treatment phase (66 in the olaparib plus chemotherapy group and 55 in the chemotherapy alone group). BRCA mutation status was known for 107 patients (either at baseline or determined retrospectively): 41 (38%) of 107 had a BRCA mutation (20 in the olaparib plus chemotherapy group and 21 in the chemotherapy alone group). Progression-free survival was significantly longer in the olaparib plus chemotherapy group (median 12.2 months [95% CI 9.7-15.0]) than in the chemotherapy alone group (median 9.6 months [95% CI 9.1-9.7) (HR 0.51 [95% CI 0.34-0.77]; p=0.0012), especially in patients with BRCA mutations (HR 0.21 [0.08-0.55]; p=0.0015). In the combination phase, adverse events that were reported at least 10% more frequently with olaparib plus chemotherapy than with chemotherapy alone were alopecia (60 [74%] of 81 vs 44 [59%] of 75), nausea (56 [69%] vs 43 [57%]), neutropenia (40 [49%] vs 29 [39%]), diarrhoea (34 [42%] vs 20 [27%]), headache (27 [33%] vs seven [9%]), peripheral neuropathy (25 [31%] vs 14 [19%]), and dyspepsia (21 [26%] vs 9 [12%]); most were of mild-to-moderate intensity. The most common grade 3 or higher adverse events during the combination phase were neutropenia (in 35 [43%] of 81 patients in the olaparib plus chemotherapy group vs 26 [35%] of 75 in the chemotherapy alone group) and anaemia (seven [9%] vs five [7%]). Serious adverse events were reported in 12 (15%) of 81 patients in the olaparib plus chemotherapy group and 16 of 75 (21%) patients in the chemotherapy alone group. Olaparib plus paclitaxel and carboplatin followed by maintenance monotherapy significantly improved progression-free survival versus paclitaxel plus carboplatin alone, with the greatest clinical benefit in BRCA-mutated patients, and had an acceptable and manageable tolerability profile. AstraZeneca. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Platinum versus platinum-combination chemotherapy in Platinum-Sensitive recurrent Ovarian Cancer: a meta-analysis using individual patient data
Annals of oncology : official journal of the European Society for Medical Oncology, 2013Co-Authors: Fharat A. Raja, Nicoletta Colombo, Nicholas Counsell, J. Pfisterer, A. Du Bois, M. K. B. Parmar, I.b. Vergote, Antonio González-martín, David S. Alberts, Marie PlanteAbstract:Background: The majority of women with Ovarian Cancer develop recurrent disease. For patients with a platinum-free interval of >6 months, platinum-based chemotherapy is a treatment of choice. The benefit of platinum-based combination chemotherapy in randomized trials varies, and a meta-analysis was carried out to gain more secure information on the size of the benefit of this treatment. Materials and methods: We initiated a systematic review and meta-analysis following a pre-specified protocol to determine whether combination chemotherapy is superior to single-agent platinum chemotherapy in women with relapsed Platinum-Sensitive Ovarian Cancer. Results: A total of five potentially eligible randomized trials were identified that had used combination-platinum chemotherapy versus single-agent platinum chemotherapy in women with relapsed Platinum-Sensitive Ovarian Cancer. For one trial (190 patients), adequate contact with the investigators could not be established. Therefore, four trials that randomly assigned 1300 patients were included, with a median follow-up of 36.1 months. Overall survival (OS) analyses were based on 865 deaths and demonstrated evidence for the benefit of combination-platinum chemotherapy (HR = 0.80; 95% CI, 0.64–1.00; P = 0.05). Progression-free survival (PFS) analyses were based on 1167 events and demonstrated strong evidence for the benefit of combination-platinum chemotherapy (HR = 0.68; 95% CI, 0.57–0.81; P< 0.001). There was no evidence of a difference in the relative effect of combination-platinum chemotherapy on either OS or PFS in patient subgroups defined by previous paclitaxel (Taxol) treatment (OS, P = 0.49; PFS, P= 0.66), duration of treatment-free interval (OS, P= 0.86; PFS, P= 0.48) or the number of previous lines of chemotherapy (OS, P= 0.21; PFS, P= 0.27). Conclusions: In this individual patient data (IPD) meta-analysis, we have demonstrated that combination-platinum chemotherapy improves OS and PFS across all subgroups. This provides the strongest evidence to date of the benefi to f combination-platinum over single-agent platinum.
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Emerging treatment strategies in recurrent Platinum-Sensitive Ovarian Cancer: Focus on trabectedin
Cancer Treatment Reviews, 2013Co-Authors: Andres Poveda, José Antonio López-guerrero, Ignacio Romero, Isabelle Ray-coquard, Nicoletta ColomboAbstract:Ovarian Cancer (OC) is the leading cause of death from gynecological malignancies. In spite of high response rates to the standard front-line treatment for advanced disease with cytoreductive surgical debulking, followed by platinum/taxane-based chemotherapy, most patients eventually relapse developing drug-resistant disease. Owing to the molecular heterogeneity, genetic instability and mutagenicity of OC, increases in survival might be achieved by translating recent insights at the morpho-molecular levels to individual therapeutic strategies. Several emerging treatments have been shown to be active in Platinum-Sensitive (PS) recurrent OC (ROC), but an optimal strategy still has not been established. Based on the recent results, it is likely that the introduction of novel non-platinum based chemotherapies and molecular targeted therapies will have a major impact on the management of ROC. Some current strategies are focused on the extension of platinum-free interval (PFI) in patients with PS, particularly in those with partially PS disease. Apparently, the PFI extension by an effective non-platinum intervention, such as trabectedin plus pegylated liposomal doxorubicin (PLD), may reduce cumulative platinum-induced toxicities leading to longer survival after the reintroduction of subsequent platinum. The introduction of novel therapies, such as the antiangiogenic monoclonal antibody bevacizumab, opens a new field of targeted therapies in this indication. In this review, we aim to outline the therapeutic potential of new emerging approaches, particularly the role of non-platinum therapy with trabectedin in combination with PLD in patients with PS ROC.
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Optimizing treatment of the partially Platinum-Sensitive Ovarian Cancer patient
Future oncology (London England), 2013Co-Authors: Nicoletta ColomboAbstract:Ovarian Cancer is the leading cause of gynecological Cancer deaths worldwide. Despite primary treatment with platinum-containing regimens, the majority of women will experience recurrent disease and subsequent death. Recurrent Ovarian Cancer remains a challenge for successful management, and the choice of second-line chemotherapy is complex due to the range of different factors that need to be considered. One of the main considerations is the platinum-free interval and, specifically, the optimal treatment for patients who are partially Platinum-Sensitive (platinum-free interval: 6-12 months). Data from the large, multicenter, randomized OVA-301 study have shown that combined trabectedin-pegylated liposomal doxorubicin (PLD) significantly prolonged median overall survival compared with PLD alone (p = 0.0027) in 214 patients with partially Platinum-Sensitive advanced relapsed Ovarian Cancer. Furthermore, in OVA-301 patients with partially Platinum-Sensitive disease who received platinum therapy immediately after disease progression (n = 94), final median overall survival was improved by 9 months (p = 0.0153) in trabectedin-PLD patients compared with PLD alone. In addition to demonstrating a survival advantage, trabectedin-PLD may also allow the treatment of patients having not yet recovered from previous platinum toxicity. In summary, the data suggest the use of combined trabectedin-PLD as a second-line treatment option in patients with partially Platinum-Sensitive recurrent Ovarian Cancer, followed by a third-line platinum-containing regimen.
Angeles Alvarez Secord - One of the best experts on this subject based on the ideXlab platform.
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Patient preference-weighted assessments using the ASCO value framework in recurrent, Platinum-Sensitive Ovarian Cancer.
Journal of Clinical Oncology, 2016Co-Authors: Jonathan Foote, Angeles Alvarez Secord, M.i. Liang, David E. Cohn, Laura J. HavrileskyAbstract:6630Background: The ASCO value framework allows comparisons of Cancer treatments based on Net Health Benefit (NHB) and cost. We aimed to assess the value of treatments for recurrent, platinum-sensi...
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Cost-effectiveness of combination versus sequential docetaxel and carboplatin for the treatment of Platinum-Sensitive, recurrent Ovarian Cancer.
Cancer, 2011Co-Authors: Laura J. Havrilesky, Robert V. Higgins, Lawrence R. Nycum, Matthew F. Kohler, Andrew Berchuck, Evan R. Myers, Robin Pokrzywinski, Dennis A. Revicki, Angeles Alvarez SecordAbstract:In a randomized controlled trial (RCT) of patients with recurrent, Platinum-Sensitive Ovarian Cancer, the combination weekly docetaxel and carboplatin was associated a with progression-free survival (PFS) of 13.7 months compared with 8.4 months for sequential, single-agent docetaxel followed by carboplatin. The objective of the current study was to construct a cost-utility model to compare these 2 regimens with the incorporation of prospectively collected quality-of-life (QoL) data. An RCT of concurrent docetaxel and carboplatin (cDC) versus docetaxel followed by carboplatin (sequential docetaxel and carboplatin [sDC]) was the basis for a Markov decision model, and the primary effectiveness outcome was PFS. Costs were estimated using US dollars based on Medicare reimbursements for chemotherapy regimens, bone marrow support, and management of adverse events. QoL data obtained using the Functional Assessment of Cancer Therapy-General questionnaire were converted to utilities. Costs and incremental cost-effectiveness ratios (ICERs) were reported in US dollars per quality-adjusted life year (QALY). Extensive 1-way sensitivity analyses and a Monte Carlo probabilistic sensitivity analysis were performed. The least expensive strategy was sDC, which cost an average of $20,381, compared with cDC, which cost an average of $25,122. cDC had an ICER of $25,239 per QALY compared with sDC. cDC remained cost-effective, with an ICER <$50,000 per QALY, over a range of costs and estimates. In Monte Carlo sensitivity analysis using a $50,000 per QALY willingness-to-pay threshold, cDC was either dominant or cost-effective with an ICER <$50,000 per QALY in 83% of simulations. Combined weekly cDC appeared to be cost-effective compared with sDC as treatment strategy for patients with Platinum-Sensitive Ovarian Cancer, even when accounting for slightly lower QoL during treatment. Copyright © 2011 American Cancer Society.
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Management of Platinum-Sensitive recurrent Ovarian Cancer: A cost-effectiveness analysis
Gynecologic oncology, 2007Co-Authors: Laura J. Havrilesky, Angeles Alvarez Secord, Shalini L Kulasingam, Evan R. MyersAbstract:We wished to compare the cost-effectiveness of three chemotherapy regimens for treatment of recurrent Platinum-Sensitive Ovarian Cancer. A Markov decision tree was constructed comparing three chemotherapy regimens: (1) carboplatin alone (C); (2) paclitaxel/carboplatin (PC); (3) gemcitabine/carboplatin (GC). Progression-free survival (PFS) and adverse event rates were estimated from published randomized controlled trials (RCTs). Costs of treatment and adverse events were obtained using Medicare reimbursement data. Estimated mean and median progression-free survival were 8.0 and 6.0 months for C, 10.1 and 7.8 months for PC, 10.5 and 8.4 months for GC, respectively. C was the least expensive strategy, costing $501 per progression-free month (PFM). PC had an incremental cost-effectiveness ratio (ICER) of $1297 per additional PFM ($15,564 per additional progression-free year (PFY)) compared to C. GC had an ICER of $23,199 per additional PFM ($278,388 per additional PFY) compared to PC. Results were insensitive to variation in the rates and costs of toxicities over clinically reasonable ranges. The model was sensitive to changes in PFS estimates. When the PFS of GC was assumed to be equivalent to that of PC, GC was strongly dominated (more expensive and no more effective) by PC due to the additional costs. Adjustment for neurotoxicity-associated quality of life (QoL) did not change rankings of strategies. PC appears to be relatively cost-effective compared to C for the treatment of recurrent Platinum-Sensitive Ovarian Cancer. GC appears to be less cost-effective compared to PC, with an ICER ten times higher.
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A comparison of combination docetaxel/carboplatin versus sequential docetaxel then carboplatin in patients with recurrent Platinum-Sensitive Ovarian Cancer
Journal of Clinical Oncology, 2006Co-Authors: Angeles Alvarez Secord, Laura J. Havrilesky, Robert V. Higgins, Lawrence R. Nycum, Matthew F. Kohler, L. E. Puls, Robert W. Holloway, John T. Soper, Fidel A. Valea, Andrew BerchuckAbstract:5092 Background: Combination paclitaxel and platinum-based chemotherapy has been shown to improve survival in patients with recurrent Platinum-Sensitive Ovarian Cancer. However, the incidence of ne...
Andrew Berchuck - One of the best experts on this subject based on the ideXlab platform.
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Cost-effectiveness of combination versus sequential docetaxel and carboplatin for the treatment of Platinum-Sensitive, recurrent Ovarian Cancer.
Cancer, 2011Co-Authors: Laura J. Havrilesky, Robert V. Higgins, Lawrence R. Nycum, Matthew F. Kohler, Andrew Berchuck, Evan R. Myers, Robin Pokrzywinski, Dennis A. Revicki, Angeles Alvarez SecordAbstract:In a randomized controlled trial (RCT) of patients with recurrent, Platinum-Sensitive Ovarian Cancer, the combination weekly docetaxel and carboplatin was associated a with progression-free survival (PFS) of 13.7 months compared with 8.4 months for sequential, single-agent docetaxel followed by carboplatin. The objective of the current study was to construct a cost-utility model to compare these 2 regimens with the incorporation of prospectively collected quality-of-life (QoL) data. An RCT of concurrent docetaxel and carboplatin (cDC) versus docetaxel followed by carboplatin (sequential docetaxel and carboplatin [sDC]) was the basis for a Markov decision model, and the primary effectiveness outcome was PFS. Costs were estimated using US dollars based on Medicare reimbursements for chemotherapy regimens, bone marrow support, and management of adverse events. QoL data obtained using the Functional Assessment of Cancer Therapy-General questionnaire were converted to utilities. Costs and incremental cost-effectiveness ratios (ICERs) were reported in US dollars per quality-adjusted life year (QALY). Extensive 1-way sensitivity analyses and a Monte Carlo probabilistic sensitivity analysis were performed. The least expensive strategy was sDC, which cost an average of $20,381, compared with cDC, which cost an average of $25,122. cDC had an ICER of $25,239 per QALY compared with sDC. cDC remained cost-effective, with an ICER <$50,000 per QALY, over a range of costs and estimates. In Monte Carlo sensitivity analysis using a $50,000 per QALY willingness-to-pay threshold, cDC was either dominant or cost-effective with an ICER <$50,000 per QALY in 83% of simulations. Combined weekly cDC appeared to be cost-effective compared with sDC as treatment strategy for patients with Platinum-Sensitive Ovarian Cancer, even when accounting for slightly lower QoL during treatment. Copyright © 2011 American Cancer Society.
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A comparison of combination docetaxel/carboplatin versus sequential docetaxel then carboplatin in patients with recurrent Platinum-Sensitive Ovarian Cancer
Journal of Clinical Oncology, 2006Co-Authors: Angeles Alvarez Secord, Laura J. Havrilesky, Robert V. Higgins, Lawrence R. Nycum, Matthew F. Kohler, L. E. Puls, Robert W. Holloway, John T. Soper, Fidel A. Valea, Andrew BerchuckAbstract:5092 Background: Combination paclitaxel and platinum-based chemotherapy has been shown to improve survival in patients with recurrent Platinum-Sensitive Ovarian Cancer. However, the incidence of ne...
Salomon M. Stemmer - One of the best experts on this subject based on the ideXlab platform.
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Comparison of Poly (ADP-ribose) Polymerase Inhibitors (PARPis) as Maintenance Therapy for Platinum-Sensitive Ovarian Cancer: Systematic Review and Network Meta-Analysis.
Cancers, 2020Co-Authors: Amos Stemmer, Salomon M. Stemmer, Inbal Shafran, Dalia TsorefAbstract:Three PARPis (olaparib, niraparib and rucaparib) are currently FDA-approved as maintenance therapy in newly diagnosed and recurrent Ovarian Cancer. However, thus far, no trial has compared the three approved PARPis in the overall population, in patients with BRCA mutations, or in those with wild-type BRCA. A frequentist network meta-analysis was used for indirect comparisons between the different PARPis with respect to progression free survival (PFS), overall survival (OS), and adverse events. Overall, six randomized clinical trials involving 2,770 patients, were included in the analysis. Results from the indirect comparisons revealed no statistically significant differences between the three PARPis with respect to PFS or OS in the entire population and in patients with mutated and wild-type BRCA, separately. Niraparib showed a statistically significant increased risk for grade 3 and 4 thrombocytopenia (risk-difference [RD] from placebo: 0.3; 95% confidence interval [CI], 0.27‒0.34) and any grade neutropenia (RD from placebo: 0.22; 95% CI, 0.18‒0.25) as compared with the other PARPis. No statistically significant difference was found between the three PARPis with respect to PFS or OS (overall and in subpopulations by BRCA status). There is, however, a statistical difference in toxicity as niraparib is associated with a greater risk for thrombocytopenia and neutropenia.
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Comparison of poly(ADP-ribose) polymerase inhibitors (PARPi's) as maintenance therapy for Platinum-Sensitive Ovarian Cancer: Systematic review and network meta-analysis.
Journal of Clinical Oncology, 2020Co-Authors: Amos Stemmer, Dalia Tsoref, Salomon M. StemmerAbstract:e18070Background: Over the past decade, 3 PARPi's (olaparib, niraparib and rucaparib) have been approved by the FDA as maintenance therapy for recurrent Ovarian Cancer. However, thus far, no trial ...