Olaparib maintenance monotherapy in platinum-sensitive, relapsed ovarian cancer without germline BRCA mutations: OPINION Phase IIIb study design

2019 ◽  
Vol 15 (32) ◽  
pp. 3651-3663
Author(s):  
Andres M Poveda ◽  
Richard Davidson ◽  
Christopher Blakeley ◽  
Alvin Milner
Keyword(s):  
Ovarian Cancer ◽  
Brca2 Mutation ◽  
Progression Free Survival ◽  
Open Label ◽  
Brca Mutations ◽  
Clinical Trial Registration ◽  
Free Survival ◽  
Platinum Sensitive ◽  
Platinum Based Chemotherapy ◽  
Phase Iiib

The poly(ADP-ribose) polymerase inhibitor olaparib (Lynparza™) is approved for maintenance treatment of platinum-sensitive relapsed ovarian cancer. OPINION is a single-arm, open-label, multicenter, Phase IIIb study to assess the efficacy and safety of olaparib tablet maintenance therapy in women with high-grade serous or endometrioid platinum-sensitive relapsed ovarian cancer without a germline BRCA1 or BRCA2 mutation. Eligible patients should have received ≥2 prior lines of platinum-based chemotherapy and be in complete or partial response following their most recent course or have no evidence of disease. Patients will receive olaparib tablets (300 mg twice daily) until disease progression, unacceptable toxicity or another discontinuation criterion. The primary end point is investigator-assessed progression-free survival; secondary end points include progression-free survival according to tumor homologous recombination deficiency status. Clinical trial registration: NCT03402841.

Phase II consolidation trial with anti-Lewis-Y monoclonal antibody (hu3S193) in platinum-sensitive ovarian cancer after a second remission

2021 ◽  
pp. ijgc-2020-002239
Author(s):  
Oren Smaletz ◽  
Gustavo Ismael ◽  
Maria Del Pilar Estevez-Diz ◽  
Ivana L O Nascimento ◽  
Ana Luiza Gomes de Morais ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Monoclonal Antibody ◽  
Epithelial Ovarian Cancer ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Complete Response ◽  
Free Survival ◽  
Platinum Sensitive ◽  
Platinum Based Chemotherapy ◽  
Lewis Y

ObjectiveTo investigate the efficacy and safety of hu3S193, a humanized anti-Lewis-Y monoclonal antibody, as a consolidation strategy in patients with platinum-sensitive recurrent epithelial ovarian cancer who achieved a second complete response after salvage platinum-doublet chemotherapy.MethodsThis single-arm phase II study accrued patients with recurrent epithelial ovarian cancer with Lewis-Y expression by immunohistochemistry who had achieved a second complete response after five to eight cycles of platinum-based chemotherapy. Patients received intravenous infusions of hu3S193, 30 mg/m2 every 2 weeks starting no more than 8 weeks after the last dose of chemotherapy and continuing for 12 doses, until disease progression, or unacceptable toxicity. The primary endpoint was progression-free survival of the second remission. Secondary objectives were safety and pharmacokinetics.ResultsTwenty-nine patients were enrolled. Most had a papillary/serous histology tumor (94%), stage III disease at diagnosis (75%), and five (17%) underwent secondary cytoreduction before salvage chemotherapy. Two patients were not eligible for efficacy but were considered for toxicity analysis. Eighteen patients (62%) completed the full consolidation treatment while nine patients progressed on treatment. At the time of analysis, 23 patients (85%) of the eligible population had progressed and seven of these patients (26%) had died. Median progression-free survival of the second remission was 12.1 months (95% CI: 10.6–13.9), with a 1-year progression-free survival of the second remission rate of 50.1%. The trial was terminated early since it was unlikely that the primary objective would be achieved. The most commonly reported treatment-related adverse events were nausea (55%) and vomiting (51%).ConclusionsHu3S193 did not show sufficient clinical activity as consolidation therapy in patients with recurrent epithelial ovarian cancer who achieved a second complete response after platinum-based chemotherapy.Trial registrationNCT01137071.

L-MOCA: An open-label study of olaparib maintenance monotherapy in platinum-sensitive relapsed ovarian cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17526-e17526
Author(s):  
Qing-lei Gao ◽  
Jianqing Zhu ◽  
Weidong Zhao ◽  
Yi Huang ◽  
Ruifang An ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Disease Progression ◽  
Brca Mutation ◽  
Progression Free Survival ◽  
Primary Analysis ◽  
Open Label ◽  
Platinum Sensitive ◽  
Kaplan Meier ◽  
Platinum Based Chemotherapy ◽  
Full Analysis

e17526 Background: In patients with platinum-sensitive recurrent serous ovarian cancer, maintenance monotherapy with the poly (ADP-ribose) polymerase inhibitor (PARPi) olaparib, significantly improves progression-free survival (PFS) versus placebo. This is the first study to evaluate the efficacy and tolerability of the olaparib (Lynparza), an oral PARPi, in patients with platinum-sensitive relapsed (PSR) ovarian cancer, carried out exclusively in Asia. Methods: In this open-label, single arm trial, patients with PSR high grade epithelial ovarian cancer who had received ≥2 previous lines of platinum-based chemotherapy with a response, were enrolled from 28 centres in China and Malaysia. All patients received oral olaparib (300 mg) tablet twice daily until disease progression or unacceptable toxicity. The primary endpoint was PFS assessed by investigator according to RECIST 1.1 criteria. Secondary endpoints included time to TFST, PFS2, TSST, OS, and safety endpoints included adverse events (AEs). Subgroup analysis of PFS was examined by BRCA status. Data were summarized by descriptive statistics; time-to-event endpoints were analyzed using Kaplan-Meier method. Primary analysis was performed when 60% of PFS events had been achieved. Results: Between 2018 and 2020, the 224 patients recruited into this study received oral olaparib (full analysis set). 224 patients (91.5% from China and 8.5% from Malaysia) provided BRCA mutation status by blood and tissue testing. 47.3% patients were BRCAm, 41.1% patients were gBRCAm,52.2% patients were BRCAwt and 0.4% patients were BRCA unknown. 35.7% patients had received ＞2 lines of chemotherapy. At data cut-off (Dec 25th, 2020), 139 patients had disease progression; median PFS (mPFS) was 16.1 (95% CI 13.3-18.3) m in all patients. The mPFS was 21.2m, 21.4m and 11.0m in BRCAm, gBRCA and BRCAwt subgroups, respectively. The overall incidence of any AE and SAE was 99.1% and 25.4%, respectively. There were 9.4% patients who discontinued therapy due to the treatment related AE. The most common AEs were anemia, nausea and vomiting. Conclusions: The L-MOCA study demonstrates olaparib maintenance treatment is effective and well tolerated in Asian PSR ovarian cancer patients regardless of BRCA status. Clinical trial information: NCT03534453. [Table: see text]

Cytoreductive surgery followed by chemotherapy and olaparib maintenance in BRCA 1/2 mutated recurrent ovarian cancer: a retrospective MITO group study

2021 ◽  
pp. ijgc-2020-002343
Author(s):  
Sabrina Chiara Cecere ◽  
Lucia Musacchio ◽  
Michele Bartoletti ◽  
Vanda Salutari ◽  
Laura Arenare ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Cytoreductive Surgery ◽  
Response Rate ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Free Survival ◽  
Platinum Sensitive ◽  
Free Interval ◽  
Platinum Based Chemotherapy

IntroductionThe role of cytoreductive surgery in the poly-ADP ribose polymerase inhibitors era is not fully investigated. We evaluated the impact of surgery performed prior to platinum-based chemotherapy followed by olaparib maintenance in platinum-sensitive BRCA-mutated recurrent ovarian cancer.MethodsThis retrospective study included platinum-sensitive recurrent ovarian cancer BRCA-mutated patients from 13 Multicenter Italian Trials in Ovarian cancer and gynecological malignancies centers treated between September 2015 and May 2019. The primary outcomes were progression-free survival and overall survival. Data on post-progression treatment was also assessed.ResultsAmong 209 patients, 72 patients (34.5%) underwent cytoreductive surgery followed by platinum-based chemotherapy and olaparib maintenance, while 137 patients (65.5%) underwent chemotherapy treatment alone. After a median follow-up of 37.3 months (95% CI: 33.4 to 40.8), median progression-free survival in the surgery group was not reached, compared with 11 months in patients receiving chemotherapy alone (P<0.001). Median overall survival was nearly double in patients undergoing surgery before chemotherapy (55 vs 28 months, P<0.001). Post-progression therapy was assessed in 127 patients: response rate to chemotherapy was 29.2%, 8.8%, and 9.0% in patients with platinum-free interval >12 months, between 6 and 12 months, and <6 months, respectively.ConclusionCytoreductive surgery performed before platinum therapy and olaparib maintenance was associated with longer progression-free survival and overall survival in BRCA-mutated platinum-sensitive relapsed ovarian cancer patients. In accordance with our preliminary results, the response rate to chemotherapy given after progression during olaparib was associated with platinum-free interval.

Panitumumab in platinum-sensitive epithelial ovarian cancer patients with KRAS wild-type: The PROVE-study, a phase II randomized multicenter study of the North-Eastern German Society of Gynaecologic Oncology.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5558-5558 ◽  
Author(s):  
Radoslav Chekerov ◽  
Peter Klare ◽  
Petra Krabisch ◽  
Jochem Potenberg ◽  
Georg Heinrich ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Ca 125 ◽  
Wild Type ◽  
Skin Reactions ◽  
Free Survival ◽  
Platinum Sensitive ◽  
Platinum Based Chemotherapy

5558 Background: For ovarian cancer (OC) patients with platinum-sensitive recurrence the addition of new biologic agents to chemotherapy may improve survival. Panitumumab is a fully human monoclonal antibody specific to the epidermal growth factor receptor (EGFR). The purpose of this trial was to investigate the therapeutic efficacy of panitumumab in the combination with carboplatin-based chemotherapy in relation to the respective standard combination in patients with a KRAS wildtype with platinum-sensitive recurrent ovarian cancer (NCT01388621). Methods: Major eligibility criteria were pretreated platinum-sensitive epithelial ovarian/ fallopian/ peritoneal cancer and no more than 2 prior treatments for this disease. Only patients with measurable disease or elevated CA125 and with KRAS wild type were eligible. Patients were treated with Carboplatin AUC4/Gemcitabine 1000 mg/m² or Carboplatin AUC5/PLD 40 mg/m² and randomized to panitumumab 6 mg/kg day 1 and day 15, every 3 or 4 weeks. Tumor assessment was performed at baseline and at every third cycle according to CT-scan and CA-125 criteria. Results: In this multi-institutional phase II trial 102 patients were randomized and 96 enrolled for the final analysis. Progression-free survival in the intention-to-treat population (N=96) was 9.5 vs. 10.7 months (HR 0.829, 95%CI of 8.5-11.6 months vs 8.5-13.1 months) for the experimental vs. standard arm, p=0.45. Data of overall survival are not jet evaluable. The most common treatment related grade 3+ toxicities included hematologic toxicity (54%), skin reactions (18%) and gastrointestinal events (16%). Conclusions: The addition of panitumumab to platinum-based chemotherapy for recurrent ovarian cancer does not influence efficacy and progression-free survival in platinum sensitive patients, while no new additional toxicity aspects for panitumumab were evaluated. Clinical trial information: NCT01388621.

scholarly journals Estimating long-term overall survival with olaparib as maintenance therapy in patients with newly diagnosed advanced ovarian cancer with BRCA mutations

2021 ◽  
Vol 17 (3) ◽  
pp. 97-105
Author(s):  
N. A. Avxentyev ◽  
S. V. Khokhlova ◽  
M. Yu. Frolov ◽  
A. S. Makarov
Keyword(s):  
Ovarian Cancer ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
First Line ◽  
Brca Mutations ◽  
Free Survival ◽  
Platinum Sensitive ◽  
Line Chemotherapy

Background. According to randomized clinical trial SOLO1 olaparib statistically significantly improves progression-free survival versus placebo as a maintenance monotherapy in patients aged 18 and over with newly diagnosed advanced ovarian cancer with BRCA mutations, who had response to first-line chemotherapy. As the data on overall survival (OS) in this trial remains interim it is still uncertain whether treatment with olaparib can provide any benefits in terms of OS.Objective: to evaluate a long-term OS for olaparib versus placebo as a maintenance monotherapy in patients with newly diagnosed advanced ovarian cancer with BRCA mutations, who had response to first-line chemotherapy.Materials and methods. A 10-year mathematic model of disease progression and survival on olaparib versus placebo was developed. Modelling was based on data on progression-free survival from SOLO1 trial and data on OS after platinum-sensitive and platinum-resistant relapses from OCEANS and AURELIA trials. Additionally, patients who haven’t been treated with olaparib after first-line therapy in base-case scenario were assumed to get olaparib as a second-line treatment after platinum-sensitive relapse; mortality modelling for these patients was based on data from SOLO2 trial.Results. Median OS for olaparib was 107 months versus 66 months for placebo. 46 % of patients treated with olaparib were alive by the end of 10-year modelling period, but only 28 % patients from the placebo group. Hazard ratio of death for olaparib versus placebo was 0.64 (95 % confidence interval 0.49–0.84). Probabilistic sensitivity analysis showed robustness of these results.Conclusion. Using olaparib as a maintenance therapy in patients with newly diagnosed advanced ovarian cancer with BRCA mutations, who had response on first line chemotherapy, statistically significantly reduces risk of death by 36 %, compared to placebo.

Overall survival and updated progression-free survival results from a randomized phase 2 trial comparing the combination of olaparib and cediranib against olaparib alone in recurrent platinum-sensitive ovarian cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5535-5535 ◽  
Author(s):  
Joyce F. Liu ◽  
William Thomas Barry ◽  
Michael J. Birrer ◽  
Jung-min Lee ◽  
Ronald J. Buckanovich ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Brca Mutation ◽  
Parp Inhibitor ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Open Label ◽  
Free Survival ◽  
Angiogenic Therapy ◽  
Platinum Sensitive

5535 Background: We previously reported that the combination of cediranib (ced) and olaparib (olap) improved progression-free survival (PFS) and overall response rates (ORR) in women with recurrent platinum-sensitive (plat-sens) high-grade serous (HGS) or BRCA-related ovarian cancer (OvCa) (NCT 01116648). We conducted an updated PFS and overall survival (OS) analysis. Methods: Patients (pts) across 9 centers were randomized 1:1 in this Ph 2 open label study to Olap (olap 400 mg capsules BID) or Ced/Olap (olap 200 mg capsules BID; ced 30 mg daily), stratified by BRCA status and prior anti-angiogenic therapy. Eligibility included pts with recurrent plat-sens HGS or BRCA-related OvCa. Pts had measurable disease by RECIST 1.1, PS 0 or 1, and the ability to take POs. No prior anti-angiogenics in the recurrent setting or prior PARP inhibitor was allowed. PFS was defined as time from randomization to radiographic progression or death. OS was defined as time from randomization to death. Results: Pts were enrolled from Oct 2011 to Jun 2013: 46 to Olap, 44 to Ced/Olap. 48 pts were known BRCA carriers (25 Olap; 23 Ced/Olap). As of Dec 21, 2016, 67 pts had a PFS event, and 52 pts had an OS event. Updated median PFS was 8.2 mos for Olap and 16.5 mos for Ced/Olap (HR 0.50, 95% CI 0.30-0.83, p=0.007). Median OS was 33.3 mos for Olap and 44.2 mos for Ced/Olap (HR 0.64, 95% CI 0.36-1.11, p=0.11). Within known germline BRCA mut carriers, updated PFS was 16.5 vs 16.4 mos (HR 0.75, p=0.42), and OS was 40.1 vs 44.2 mos (HR 0.79, p=0.55) for Olap and Ced/Olap, respectively. In pts without known germline BRCA mut, updated PFS was 5.7 vs 23.7 mos (HR 0.32, p=0.002), and OS was 23.0 vs 37.8 mos (HR 0.48, p=0.074). Conclusions: Updated PFS results consistently demonstrated that Ced/Olap significantly extended PFS compared to Olap in the overall population of women with plat-sens OvCa. In this Phase 2 study not powered to detect OS diferences, there was a trend towards OS improvement with Ced/Olap, particularly in pts without a known germline BRCA mutation. Results from ongoing studies of this oral combination in OvCa are of clinical interest. Clinical trial information: NCT 01116648.

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.

scholarly journals Prognostic Value of TNFR2 and STAT3 among High-Grade Serous Ovarian Cancer Survivors According to Platinum Sensitivity

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 526
Author(s):  
Janisha Silva Raju ◽  
Nor Haslinda Abd. Aziz ◽  
Ghofraan Abdulsalam Atallah ◽  
Chew Kah Teik ◽  
Mohamad Nasir Shafiee ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Protein Expression ◽  
Ovarian Tissue ◽  
Progression Free Survival ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Free Survival ◽  
Platinum Sensitive ◽  
Platinum Based Chemotherapy ◽  
Survival Interval

This study’s goal was to determine the protein expression level of tumour necrosis factor receptor 2 (TNFR2) and signal transducer and activator of transcription 3 (STAT3) in high-grade serous ovarian cancer (HGSC) tissues in relation to the platinum-based chemotherapy response and the prognosis outcome. A total of 25 HGSC patients underwent primary surgical debulking followed by first-line adjuvant platinum-based chemotherapy. Tissue microarray (TMA) slides were constructed utilising archived formalin fixed paraffin embedded (FFPE). The protein expression of TNFR2 and STAT3 were analysed using immunohistochemistry (IHC) staining and subsequently were correlated to the clinicopathological characteristics, platinum sensitivity as well as the duration of progression-free survival. About 14 out of 25 patients (56.0%) were platinum-sensitive. The progression free survival was significantly longer in the platinum-sensitive (PS) group when compared to those with the platinum-resistant group (PR), p = 0.0001. Among patients with TNFR2 strong expression on ovarian tissue, there was a significantly longer progression-free survival interval of 540 days in the PS group compared to PR, p = 0.0001. Patients with STAT3 expression also showed significantly better progression-free survival of 660 days in the PS group when compared to the PR group, p = 0.0001. In conclusion, patients with strong TNFR2 and STAT3 expression in the ovarian tissue had significantly longer progression-free survival interval in the PS group. Nevertheless, further research with a larger number of tissues may be required to demonstrate further significant differences.

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