scholarly journals Olaparib maintenance therapy in patients (pts) with platinum-sensitive relapsed (PSR) ovarian cancer (OC) and stable disease (SD) following platinum-based chemotherapy

2018 ◽  
Vol 29 ◽  
pp. viii340
Author(s):  
A.M. Oza ◽  
D. Cibula ◽  
A. Oaknin ◽  
C. Poole ◽  
R.H.J. Mathijssen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Maintenance Therapy ◽  
Stable Disease ◽  
Platinum Sensitive ◽  
Platinum Based Chemotherapy

Phase II study of DMXAA combined with carboplatin and paclitaxel in recurrent ovarian cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5032-5032 ◽  
Author(s):  
H. Gabra
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Stable Disease ◽  
Phase Ii Study ◽  
Objective Response ◽  
Recurrent Ovarian Cancer ◽  
Figo Stage ◽  
Vascular Disrupting Agent ◽  
Platinum Sensitive ◽  
Platinum Based Chemotherapy

5032 Background: DMXAA (AS1404) is a small-molecule vascular disrupting agent, which in animal models shows additive or supra-additive effects with cytotoxics, including taxanes and platinum agents. This phase II study evaluated DMXAA in combination with carboplatin and paclitaxel in recurrent platinum-sensitive ovarian cancer patients with a progression-free interval of more than 6 months after response to platinum-based chemotherapy. Methods: Patients had first diagnosed disease FIGO stage Ic-IV, with presence of recurrent disease confirmed by imaging. Patients were randomised 1:1 to receive up to 6 cycles of carboplatin (AUC 6 mg/ml × min) and paclitaxel (175 mg/m2) with or without DMXAA (1200 mg/m2). Safety assessments included EKG, adverse events, laboratory screens and ophthalmic exam. Efficacy endpoints are objective response rates, time to progression, duration of response and stable disease, and median and 1-year survival. Results: 55 patients have been enrolled to date from a planned total of ∼70. Initial safety findings in the two arms are comparable. Preliminary investigator-assessed RECIST response data show the following unconfirmed outcomes: of 17 patients in the DMXAA arm, there are 10 with partial responses (PRs), 7 with stable disease (SD) and 0 with progressive disease (PD); of 14 patients in the control arm, there are 8 PRs, 6 SDs and 0 PDs. Conclusions: Initial safety findings suggest that addition of DMXAA to standard doses of carboplatin and paclitaxel did not add significantly to toxicity. Efficacy assessments are ongoing to determine the value of the triple combination in recurrent ovarian cancer. No significant financial relationships to disclose.

Real-world treatment patterns of maintenance therapy in platinum-sensitive recurrent epithelial ovarian cancer: Are some patients missing out?

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18042-e18042
Author(s):  
Haley Moss ◽  
Angeles Alvarez Secord ◽  
Jessica Perhanidis ◽  
Carol Hawkes
Keyword(s):  
Ovarian Cancer ◽  
Maintenance Therapy ◽  
Active Surveillance ◽  
Real World ◽  
Brca Mutation ◽  
Treatment Patterns ◽  
World Population ◽  
Brca Mutations ◽  
Platinum Sensitive ◽  
Platinum Based Chemotherapy

e18042 Background: The clinical utility of maintenance therapy (MT) for patients with platinum-sensitive recurrent ovarian cancer (PSROC) has been validated in several clinical trials. We assessed real world treatment patterns using a US nationwide electronic health record database. Methods: A retrospective study of patients with PSROC between March 2017 and July 2019 was conducted using the Flatiron Health database. This longitudinal, demographically and geographically diverse de-identified database covers > 2.2 million oncology patients in > 280 cancer clinics. Patients were excluded if second or third line (2L or 3L) platinum-based chemotherapy (PBT) regimens included less than four or more than eight cycles of platinum. Information regarding somatic or germline BRCA mutations and homologous recombination deficiency (HRD) were obtained. Results: 2292 patients with PSROC were identified (had 2L or 3L treatment); 1214 of these received PBT at recurrence; 610 completed the PBT for recurrence on or after March 2017; 351 received 4–8 cycles of PBT; 225 patients had ≥2 months of active surveillance or were receiving MT of PARPi or bevacizumab (B) and were included in this analysis. 183 patients (80%) had BRCA testing and 14 patients (6%) had HRD testing. 46 (20%) had a germline or somatic BRCA mutations (t BRCA), 134 (59%) had a wildtype wt BRCA gene, and 48 (21%) were unknown. Of patients with tBRCA, 63% received a PARP inhibitor (PARPi), 17% received B, 20% received active surveillance. Of patients with wt BRCA, 40% received a PARPi, 24% received B, and 37% received active surveillance. Olaparib was the most commonly used PARPi among tBRCA patients (26%), while niraparib was most commonly used among wt BRCA patients (21%). MT was more common in younger patients, those with a better performance status and with a BRCA mutation. MT use trend increased by 21% during the study period. As PARPi use increased, the use of active surveillance as a post-platinum regimen decreased during the later time periods (Table). Conclusions: In this real world population, the majority of patients with PSROC are receiving maintenance therapy. While genetic testing is improving, universal testing of all patients with ovarian cancer remains the goal. The results provide insight into the shifting treatment patterns for patients with ovarian cancer. [Table: see text]

Efficacy of niraparib maintenance therapy in Chinese women with platinum-sensitive recurrent ovarian cancer with and without secondary cytoreductive surgery: Results from the NORA trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5534-5534
Author(s):  
Lingying Wu ◽  
Xiaohua Wu ◽  
Jianqing Zhu ◽  
Rutie Yin ◽  
Jiaxin Yang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Maintenance Therapy ◽  
Cytoreductive Surgery ◽  
Chinese Women ◽  
Group Analysis ◽  
Recurrent Ovarian Cancer ◽  
Phase Iii ◽  
Platinum Sensitive ◽  
Secondary Cytoreductive Surgery ◽  
Platinum Based Chemotherapy

5534 Background: NORA is the first, phase III, randomized controlled trial (RCT) that demonstrated individualized starting dose regimen of niraparib, which significantly improved PFS in Chinese patients with platinum-sensitive recurrent ovarian cancer (PSROC). This sub-group analysis evaluated the efficacy of niraparib maintenance therapy with and without secondary cytoreductive surgery (SCS) in PSROC. Methods: The NORA phase III RCT included adult (≥18 years) Chinese women with PSROC who were randomized in a 2:1 ratio to receive oral niraparib (n = 177) or matched placebo (n = 88). This retrospective subgroup analysis was based on the progression-free survival (PFS) of niraparib maintenance therapy in these two groups of patients with PSROC, patients with SCS, and patients without SCS. The PFS was assessed by blinded independent central review. The Kaplan-Meier (KM) estimator and log-rank test were performed to calculate the median PFS time. Results: Of the 265 evaluable patients, 69 (26.0%) patients received the SCS (niraparib, n = 48; placebo, n = 21), and 196 (74.0%) patients were without SCS (niraparib, n = 129; placebo, n = 67). Among patients with and without SCS, baseline characteristics for BRCA mutation were 26.1% vs 41.8%, complete response to last platinum-based chemotherapy were 68.1% vs 43.9%, time (6-12 months) to progression after penultimate therapy were 23.2% vs 34.7%, respectively. Treatment with niraparib led to a significant reduction of risk to disease progression compared with placebo in patients with SCS (Hazard ratio [95% CI]: 0.32 [0.13–0.78]; P = 0.0102) and without SCS (0.34 [0.23–0.50]; P< 0.001). Moreover, in the subgroups of patients who received SCS, niraparib maintenance therapy had a significantly longer PFS compared with placebo (Median [95% CI]: not reached [18.33 – not estimable] vs 5.75 months [3.68 – not estimable]; P = 0.0102). This trend was also similar in the subgroup of patients who did not receive SCS (Median [95% CI]: 10.28 months [7.49 – 18.37] vs 4.90 months [3.71 – 5.52]; P < 0.0001). Conclusions: The results from this retrospective sub-group analysis revealed that niraparib maintenance therapy provided significant clinical efficacy in patients with PSROC, irrespective of SCS. Clinical trial information: NCT03705156.

scholarly journals Safety Profile of Niraparib as Maintenance Therapy for Ovarian Cancer: A Systematic Review and Meta-Analysis

2022 ◽  
Vol 29 (1) ◽  
pp. 321-336
Author(s):  
Antonia Pagkali ◽  
Ioannis Mamais ◽  
Adamantios Michalinos ◽  
Aris P. Agouridis
Keyword(s):  
Ovarian Cancer ◽  
Adverse Effects ◽  
Maintenance Therapy ◽  
Safety Profile ◽  
Meta Analysis ◽  
Platinum Sensitive ◽  
Dichotomous Data ◽  
Platinum Based Chemotherapy ◽  
Grade 3 ◽  
Randomised Controlled

Background: Patients with epithelial ovarian cancer (EOC), treated with niraparib maintenance, present with haematological and gastrointestinal toxicities. Limited data exist on niraparib safety assessment. Objective: To evaluate niraparib safety profile, as maintenance therapy, in women with platinum-sensitive EOC. Methods: PubMed and Cochrane searches were carried out up to April 2021 for randomised controlled trials (RCTs) evaluating niraparib versus placebo in EOC patients with a response to platinum-based chemotherapy. Regarding the meta-analysis, for dichotomous data, the pooled risk ratio (RR) was calculated. Results: A total of 1539 patients from three RCTs revealed that niraparib-treated patients are associated with a significantly higher risk of any grade of nausea (RR, 2.15; 95% CI, 1.86 to 2.48), fatigue (RR, 1.26; 95% CI, 1.05 to 1.52, p < 0.00001), anemia (RR, 6.86; 95% CI, 2.54 to 18.52, p = 0.0001), thrombocytopenia (RR, 7.02; 95% CI, 1.68 to 29.38, p < 0.00001), vomiting (RR, 2.51; 95% CI, 1.50 to 4.19, p = 0.0005), neutropenia (RR, 2.96; 95% CI, 1.13 to 7.73, p < 0.00001), headache (RR, 2.08; 95% CI, 1.57 to 2.74, p < 0.00001), constipation (RR, 2.10; 95% CI, 1.72 to 2.57, p < 0.00001) and insomnia (RR, 2.48; 95% CI, 1.52 to 2.89, p = 0.0003) when compared with placebo. For grade 3 or 4 adverse effects, significantly higher risk was only noted for fatigue (RR,6.25; 95% CI, 1.70 to 23.05, p = 0.006), anemia (RR, 16.23; 95% CI, 4.86 to 54.17, p < 0.00001), thrombocytopenia (RR, 35.12; 95% CI, 12.23 to 100.82, p < 0.00001) and neutropenia episodes (RR, 6.35; 95% CI, 2.08 to 19.39, p = 0.001) for those taking niraparib. Notably, incidents of adverse effects and discontinuation rates were substantially lower among patients treated with an individualised niraparib dose than those treated with the standard one. Efficacy was not reduced, and no treatment-related deaths occurred during the included trials. Conclusion: Niraparib is considered an effective and well-tolerated choice, with an improved safety profile, for the maintenance treatment of EOC patients.

Dora: A randomized phase II multicenter maintenance study of olaparib alone or olaparib in combination with durvalumab in platinum responsive advanced triple-negative breast cancer (aTNBC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS1113-TPS1113
Author(s):  
Sarah Sammons ◽  
Tira Jing Ying Tan ◽  
Tiffany A. Traina ◽  
Sung-Bae Kim ◽  
Young-Hyuck Im ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Maintenance Therapy ◽  
Phase Ii ◽  
Clinical Benefit ◽  
Single Agent ◽  
Phase Iii ◽  
Parp Inhibition ◽  
Platinum Sensitive ◽  
Platinum Based Chemotherapy

TPS1113 Background: PARP inhibition (PARPi) with olaparib is approved in HER2-negative germline BRCA mutant (g BRCAm) metastatic breast cancer. Maintenance PARPi in relapsed platinum-sensitive ovarian cancer improves median PFS regardless of gBRCA mutation status. Preclinical work has shown that platinum response strongly correlates with olaparib response in breast cancer models; hence, maintenance therapy trials are underway in aTNBC. PARPi modulates immune responses and enhances immunogenicity in many preclinical models. We hypothesize that olaparib either alone or in combination with the PD-L1 inhibitor durvalumab will have clinical efficacy as maintenance therapy in aTNBC subjects who have responded to platinum-based chemotherapy. Methods: DORA is a randomized, international, multicenter, phase II study designed to explore the efficacy of olaparib or olaparib in combination with durvalumab as maintenance therapy in platinum-sensitive aTNBC. 60 subjects will be enrolled following a minimum of 3 cycles of treatment with platinum-based (cisplatin or carboplatin) chemotherapy as a single agent or combination therapy in the first or second-line setting. Subjects deriving clinical benefit (CR / PR / SD) from platinum-based therapy will be eligible and randomized in a 1:1 ratio. Patients in arm 1 will receive olaparib orally 300mg BID continuously and in arm 2 will receive olaparib orally 300mg BID continuously in combination with durvalumab 1500mg IV every 4 weeks. Assessment of tumor response will be done every 8 weeks. Primary endpoint: progression-free survival. Secondary endpoints: overall survival, clinical benefit rate, safety. Correlative analyses: pre-treatment archival/fresh biopsy samples are mandated. Post-treatment tissue biopsy is requested. Serial ctDNA will be collected at baseline, staging, and progression to correlate with response and track emerging genomic alterations in a platinum sensitive cohort under the pressure of PARP inhibition. Whole exome DNA sequencing, IHC for PDL-1 and TILs will be performed on tissue samples. ClincalTrials.gov Identifier: NCT03167619. (Moore K, et al "SOLO-1: Phase III trial of maintenance olaparib following platinum-based chemotherapy in newly diagnosed patients with advanced ovarian cancer and a BRCA1/2 mutation" ESMO 2018; Abstract LBA7-PR). Clinical trial information: NCT03167619.

scholarly journals ICON 9—an international phase III randomized study to evaluate the efficacy of maintenance therapy with olaparib and cediranib or olaparib alone in patients with relapsed platinum-sensitive ovarian cancer following a response to platinum-based chemotherapy

2020 ◽  
Vol 31 (1) ◽  
pp. 134-138
Author(s):  
Osnat Elyashiv ◽  
Jonathan Ledermann ◽  
Gita Parmar ◽  
Laura Farrelly ◽  
Nicholas Counsell ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Maintenance Therapy ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Wild Type ◽  
Free Survival ◽  
Platinum Sensitive ◽  
Primary Endpoints ◽  
Platinum Based Chemotherapy

BackgroundTwo novel biological agents—cediranib targeting angiogenesis, and olaparib targeting DNA repair processes—have individually led to an improvement in ovarian cancer control. The aim of ICON9 is to investigate the combination of cediranib and olaparib maintenance in recurrent ovarian cancer following platinum-based therapy.Primary objectiveTo assess the efficacy of maintenance treatment with olaparib in combination with cediranib compared with olaparib alone following a response to platinum-based chemotherapy in women with platinum-sensitive ovarian, fallopian tube or peritoneal cancer during first relapse.Study hypothesisMaintenance therapy with cediranib and olaparib in combination is associated with improved patient outcomes compared with olaparib alone.Trial designInternational phase III randomized controlled trial. Following a response to platinum-based chemotherapy patients are randomized 1:1 to either oral olaparib and cediranib (intervention arm) or oral olaparib alone (control arm).Major inclusion criteriaPatients with a known diagnosis of high grade serous or endometrioid carcinoma of the ovary, fallopian tube or peritoneum, progressing more than 6 months after first-line platinum-based chemotherapy, who have responded to second-line platinum-based chemotherapy.Primary endpointsProgression-free and overall survival. Co-primary endpoints to be assessed using a fixed-sequence gatekeeping approach: (1) progression-free survival, all patients; (2) progression-free survival, BRCA wild type; (3) overall survival, all patients; (4) overall survival, BRCA wild type.Sample size618 patients will be recruited.Estimated dates for completing accrual and presenting resultsAccrual is expected to be completed in 2024 with presentation of results in 2025.Trial registrationClinicalTrials.gov: NCT03278717.

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