A randomized, double-blind phase III trial of niraparib maintenance treatment in patients with HRD+ advanced ovarian cancer after response to front-line platinum-based chemotherapy.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. TPS5606-TPS5606 ◽  
Author(s):  
Antonio Gonzalez-Martin ◽  
Floor Jennishens Backes ◽  
Klaus H. Baumann ◽  
Dana Meredith Chase ◽  
Mathias Konrad Fehr ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Maintenance Treatment ◽  
Advanced Ovarian Cancer ◽  
Phase Iii ◽  
Front Line ◽  
Double Blind ◽  
Phase Iii Trial ◽  
Platinum Based Chemotherapy

Use of First-Line PARP Inhibitors in Ovarian Cancer

2019 ◽  
pp. 26-29
Author(s):  
Ursula Hasler-Strub
Keyword(s):  
Ovarian Cancer ◽  
Treatment Strategies ◽  
Advanced Ovarian Cancer ◽  
Standard Of Care ◽  
Parp Inhibitors ◽  
Phase Iii ◽  
Line Treatment ◽  
Front Line ◽  
First Line ◽  
Platinum Based Chemotherapy

Platinum-based chemotherapy regimens are the mainstay of advanced ovarian cancer treatment. However, up to 85% of the patients experience recurrence under these settings. To fill this gap, novel front-line treatment strategies have been established, leading to unprecedented clinical benefits. For example, first-line bevacizumab, an anti-angiogenic agent, plus chemotherapy followed by bevacizumab maintenance, has emerged as a new standard of care for newly diagnosed high risk ovarian cancer patients. This was based on the results of the phase III GOG 0218 and ICON-7 trials. More recently, poly(ADP)-ribose polymerase (PARP) inhibitors, including niraparib, olaparib and veliparib, have offered a new treatment option as part of the front-line treatment in ovarian cancer. Here we provide an overview of three recent studies that may lead to a paradigm shift in the first-line treatment for advanced ovarian cancer.

Centralized independent disease status adjudication for maintenance treatment evaluation in advanced ovarian cancer setting: A critical analysis of the MIMOSA trial experience.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16510-e16510
Author(s):  
Simona Scartoni ◽  
Jacobus Pfisterer ◽  
Paul Sabbatini ◽  
Jonathan S. Berek ◽  
Monica Bertolotti ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Data ◽  
Maintenance Treatment ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Sensitivity Analyses ◽  
Primary Analysis ◽  
Double Blind ◽  
Abdomen Ct

e16510^ Background: Progression free survival (PFS) is an accepted surrogate of Overall Survival (OS) often used as the primary endpoint in phase III trials evaluating maintenance treatment in advanced ovarian cancer (AOC). Methods: We compare the centrally assessed PFS (PFS-CA) vsthe locally assessed PFS (PFS-LA) data collected in the Mimosa Trial, a randomized, double blind, placebo controlled, Phase III study of Abagovomab maintenance therapy in AOC patients in complete response after standard chemotherapy. PFS was assessed at pre-fixed time points by pelvis/abdomen CT scan, which were centrally and blinded reviewed by trained radiologists for radiological assessment (RA) of recurrence status and date (PFS-RA). An independent blinded committee, including one radiologist and one oncologist, reviewed all the CT scans and any additional imaging records AND/OR clinical data (when locally required for patients’management) to adjudicate the recurrence status and date (PFS-CA). PFS-CA was used for the primary analysis; sensitivity analyses were carried out on PFS-LA as well as on the strictly defined PFS-RA data. Results: 888 patients were randomized 2:1 to receive Abagovomab or placebo. In the ITT population (n = 886) time to PFS-CA was 403 and 402 days in Abagovomab and placebo group, respectively; in the sensitivity analyses time to PFS-LA was 407 and 409, and finally time to PFS-RA was 414- 487 days respectively, without any statistically significant differences between groups or PFS assessments. Conclusions: No differences were seen in PFS assessed centrally or locally when RA and clinical data are considered, whereas a slightly longer PFS was observed when it was assessed exclusively by the independent radiological review although this is not statistically different. The centralised independent assessment of recurrence status for ovarian cancer patients treated in the remission setting appears not to add value to the local blinded assessment. Clinical trial information: NCT00418574.

PAOLA-1: An ENGOT/GCIG phase III trial of olaparib versus placebo combined with bevacizumab as maintenance treatment in patients with advanced ovarian cancer following first-line platinum-based chemotherapy plus bevacizumab.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS5605-TPS5605 ◽  
Author(s):  
Isabelle Laure Ray-Coquard ◽  
Philipp Harter ◽  
Antonio Gonzalez Martin ◽  
Claire Cropet ◽  
Sandro Pignata ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Maintenance Therapy ◽  
Maintenance Treatment ◽  
Advanced Ovarian Cancer ◽  
Chemotherapeutic Agents ◽  
Phase Iii ◽  
Brca Testing ◽  
First Line ◽  
Platinum Based Chemotherapy ◽  
The Eu

TPS5605 Background: Olaparib (Lynparza) is an oral PARP inhibitor indicated in the EU for the maintenance treatment of patients (pts) with platinum-sensitive relapsed BRCA-mutated high grade serous ovarian cancer (HGSOC). Bevacizumab is an anti-VEGF monoclonal antibody indicated in the EU in first line or relapse for the treatment of OC in combination with specific chemotherapeutic agents. Bevacizumab treatment is associated with increasing hypoxia-induced homologous recombination repair deficiencies in tumor cells, and is hypothesized to increase ovarian tumor sensitivity to olaparib. Methods: PAOLA-1 (ENGOT-ov25) is a randomized, placebo-controlled trial evaluating the efficacy and safety of olaparib (tablet formulation) in pts with advanced HGSOC receiving bevacizumab maintenance therapy. Eligible pts are those in complete or partial response following first-line platinum chemotherapy plus bevacizumab, and for whom bevacizumab maintenance therapy is planned. Approximately 762 European and 24 Japanese pts will be randomized 2:1 to olaparib 300 mg twice daily or placebo for up to 24 months. All pts will receive standard maintenance care of bevacizumab (15 mg/kg every three weeks) for up to 15 months. Primary objective: PFS1 according to RECIST 1.1 Secondary objectives: PFS2, OS, Safety, PRO/QoL, TFST, TSST All pts will undergo tumor BRCA testing prior to randomization. Central BRCA testing (tumor) will be performed in five screening platforms in France. Tumor BRCA test results have to be available within two months of sample provision. PFS will be evaluated using a log-rank test stratified by response to first-line treatment and BRCA mutation status. Treatment effect hazard ratio of 0.7 is expected and final PFS1 analysis will be performed after 372 events. The first pt from eight ENGOT groups plus Japan (10 participating countries) was randomized in July 2015. As of 31 January 2017, 549 pts have been randomized. The median period between the provision of a tumor sample and returned BRCA test result is 40 days. Accrual is expected to be complete before July 2017. Clinical trial information: NCT02477644.

scholarly journals ATHENA (GOG-3020/ENGOT-ov45): a randomized, phase III trial to evaluate rucaparib as monotherapy (ATHENA–MONO) and rucaparib in combination with nivolumab (ATHENA–COMBO) as maintenance treatment following frontline platinum-based chemotherapy in ovarian cancer

2021 ◽  
pp. ijgc-2021-002933
Author(s):  
Bradley J Monk ◽  
Robert L Coleman ◽  
Keiichi Fujiwara ◽  
Michelle K Wilson ◽  
Amit M Oza ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Maintenance Treatment ◽  
Standard Treatment ◽  
Progression Free Survival ◽  
Parp Inhibitors ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Platinum Based Chemotherapy

BackgroundThe optimal treatment strategy for women with newly diagnosed ovarian cancer has yet to be determined. Poly(ADP-ribose) polymerase (PARP) inhibitors have demonstrated substantial improvement in progression-free survival as monotherapy maintenance treatment in the frontline setting versus active surveillance. Furthermore, preclinical and early clinical studies have shown that PARP inhibitors and immune checkpoint inhibitors have synergistic antitumor activity and may provide an additional therapeutic option for patients in this population.Primary ObjectivesIn women with newly diagnosed ovarian, fallopian tube, or peritoneal cancer, we wish to assess the efficacy of frontline maintenance treatment with the PARP inhibitor rucaparib versus placebo following response to platinum-based chemotherapy (ATHENA–MONO), and to assess the combination of rucaparib plus nivolumab (a programmed death receptor 1 (PD-1)–blocking monoclonal antibody) versus rucaparib alone (ATHENA–COMBO).Study Hypothesis(1) Maintenance therapy with rucaparib monotherapy may extend progression-free survival following standard treatment for ovarian cancer in the frontline setting. (2) The combination of nivolumab plus rucaparib may extend progression-free survival following standard treatment for ovarian cancer in the frontline setting compared with rucaparib alone.Trial DesignATHENA is an international, randomized, double-blind, phase III trial consisting of two independent comparisons (ATHENA–MONO and ATHENA–COMBO) in patients with newly diagnosed platinum-sensitive ovarian cancer. Patients are randomized 4:4:1:1 to the following: oral rucaparib+ intravenous nivolumab (arm A); oral rucaparib + intravenous placebo (arm B); oral placebo+ intravenous nivolumab (arm C); and oral placebo + intravenous placebo (arm D). The starting dose of rucaparib is 600 mg orally twice a day and nivolumab 480 mg intravenously every 4 weeks. ATHENA–MONO compares arm B with arm D to evaluate rucaparib monotherapy versus placebo, and ATHENA–COMBO evaluates arm A versus arm B to investigate the effects of rucaparib and nivolumab in combination versus rucaparib monotherapy. ATHENA–MONO and ATHENA–COMBO share a common treatment arm (arm B) but each comparison is independently powered.Major Inclusion/Exclusion CriteriaPatients ≥18 years of age with newly diagnosed advanced, high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancer who have achieved a response after completion of cytoreductive surgery and initial platinum-based chemotherapy are enrolled. No other prior treatment for ovarian cancer, other than the frontline platinum regimen, is permitted.Primary EndpointThe primary endpoint is investigator-assessed progression-free survival by Response Evaluation Criteria in Solid Tumors v1.1.Sample SizeApproximately 1000 patients have been enrolled and randomized.Estimated Dates for Completing Accrual and Presenting ResultsThe trial completed accrual in 2020. While dependent on event rates, primary results of ATHENA–MONO are anticipated in early 2022 and results of ATHENA–COMBO are anticipated to mature at a later date.Trial RegistrationThis trial is registered at clinicaltrials.gov (NCT03522246).

Sign in / Sign up

Export Citation Format

Share Document