scholarly journals Real-World Experience of Olaparib Maintenance in High-Grade Serous Recurrent Ovarian Cancer Patients with BRCA1/2 Mutation: A Korean Multicenter Study

2019 ◽  
Vol 8 (11) ◽  
pp. 1920 ◽  
Author(s):  
Paik ◽  
Lee ◽  
Lee ◽  
Shin ◽  
Park ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Real World ◽  
Partial Remission ◽  
Brca1 Mutation ◽  
Brca2 Mutation ◽  
Objective Response ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
High Grade ◽  
Platinum Sensitive

Background: Olaparib maintenance therapy has shown efficacy and tolerability in patients with platinum-sensitive, high-grade serous recurrent ovarian cancer (HSROC) with BRCA1/2 mutation (BRCAm). Our aim was to present real-world experience with olaparib in Korea. Method: We included HSROC patients with BRCAm treated with olaparib maintenance at four institutions in Korea between 2016 and 2018. Medical records were reviewed for clinico-pathologic characteristics, objective response, survival outcomes, and safety. Results: One hundred HSROC patients with BRCAm were included. BRCA1 mutation was present in 71 patients (71.0%), and BRCA2 mutation was present in 23 patients (23.0%). In terms of the best objective response with olaparib maintenance in 53 patients with partial remission from most recent chemotherapy, complete remission occurred in 12 (22.6%) and partial remission in four (7.5%), while 33 patients (62.3%) had stable disease. The 24 month progression-free survival was 42.4%, and 24 month overall survival was 82.1%. Grade 3 or more adverse events were as follows: anemia in 14 patients (14.0%), neutropenia in seven patients (7.0%), thrombocytopenia in two patients (2.0%), oral mucositis in one patient (1.0%), and soft tissue infection in one patient (1.0%). Conclusions: The safety and effectiveness of olaparib maintenance treatment in a real-world study were consistent with those reported in previous clinical trials.

Nonplatinum Topotecan Combinations Versus Topotecan Alone for Recurrent Ovarian Cancer: Results of a Phase III Study of the North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group

2008 ◽  
Vol 26 (19) ◽  
pp. 3176-3182 ◽  
Author(s):  
Jalid Sehouli ◽  
Dirk Stengel ◽  
Guelten Oskay-Oezcelik ◽  
Alain G. Zeimet ◽  
Harald Sommer ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Ovarian Cancer ◽  
Overall Survival ◽  
Objective Response ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Free Survival ◽  
Platinum Sensitive ◽  
Platinum Refractory

PurposeThe management of recurrent ovarian cancer remains controversial. Single-agent topotecan is an established treatment option, and preliminary evidence suggests improved tumor control by combining topotecan with etoposide or gemcitabine.Patients and MethodsWomen with relapsed ovarian cancer after primary surgery and platinum-based chemotherapy were randomly assigned to topotecan monotherapy 1.25 mg/m2/d, topotecan 1.0 mg/m2plus oral etoposide 50 mg/d, or topotecan 0.5 mg/m2/d plus gemcitabine 800 mg/m2on day 1 and 600 mg/m2on day 8 every 3 weeks. Patients were stratified for platinum-refractory and platinum-sensitive disease according to a recurrence-free interval of less or more than 12 months, respectively. The primary end point was overall survival. Secondary end points included progression-free survival, objective response rates, toxicity, and quality of life (as measured by the European Organisation for Research and Treatment of Cancer [EORTC] 30-item Quality-of-Life Questionnaire).ResultsThe trial enrolled 502 patients with a mean age of 60.5 years (± 10.2 years), 208 of whom were platinum resistant. Median overall survival was 17.2 months (95% CI, 13.5 to 21.9 months) with topotecan, 17.8 months (95% CI, 13.7 to 20.0 months) with topotecan plus etoposide (log-rank P = .7647), and 15.2 months (95% CI, 11.3 to 20.9 months) with topotecan plus gemcitabine (log-rank P = .2344). Platinum-sensitive patients lived significantly longer than platinum-refractory patients (21.9 v 10.6 months). The median progression-free survival was 7.0, 7.8, and 6.3 months, respectively. Objective response rates were 27.8%, 36.1%, and 31.6%, respectively. Patients under combined treatment were at higher risk of severe thrombocytopenia.ConclusionNonplatinum topotecan combinations do not provide a survival advantage over topotecan alone in women with relapsed ovarian cancer.

A randomized phase 2 trial comparing efficacy of the combination of the PARP inhibitor olaparib and the antiangiogenic cediranib against olaparib alone in recurrent platinum-sensitive ovarian cancer.

2014 ◽  
Vol 32 (18_suppl) ◽  
pp. LBA5500-LBA5500 ◽  
Author(s):  
Joyce Liu ◽  
William Thomas Barry ◽  
Michael J. Birrer ◽  
Jung-min Lee ◽  
Ronald J. Buckanovich ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase 1 ◽  
Parp Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Parp Inhibitors ◽  
Open Label ◽  
Angiogenic Therapy ◽  
Platinum Sensitive

LBA5500 Background: PARP inhibitors and anti-angiogenics are clinically active in recurrent ovarian cancer (OvCa). Preclinical studies suggest these agents can synergize, and a phase 1 study showed that the combination of cediranib (ced) and olaparib (olap) is well-tolerated. We therefore compared the activity of olap alone (Olap) to combined ced and olap (Ced/Olap) in treatment of recurrent platinum-sensitive (plat-sens) high-grade serous (HGS) or BRCA-related OvCa (NCT 01116648). 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. Progression-free survival (PFS) was defined as time from randomization to radiographic progression or death. With a target N=90 pts, the study was powered to detect a hazard ratio (HR) of 1.75 (median PFS 6 vs 10.5 mo). 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). At a planned interim analysis the DSMB recommended release of data. As of Jan 7, 2014, 41 pts had a PFS event. Median PFS was 9.0 mos for Olap and 17.7 mos for Ced/Olap (HR 2.9, 95% CI 1.5-5.6, p = 0.001). There were 2 complete responses (CR) and 21 partial responses (PR) in pts on Olap (56% objective response rate, ORR) and 3 CRs and 33 PRs in pts on Ced/Olap (84% ORR, p = 0.008). The overall rate of Gr3/4 toxicity was higher for pts on Ced/Olap (70%) than on Olap (7%). Differentially occurring toxicities included fatigue (27% Ced/Olap vs 7% Olap), diarrhea (23% vs 0%), and hypertension (39% vs 0%). Updated efficacy and exploratory subgroup analyses will be presented. Conclusions: Combined Ced/Olap significantly extended PFS and ORR compared to Olap in plat-sens OvCa. Further studies of this oral combination in plat-sens OvCa are warranted. Clinical trial information: NCT01116648.

scholarly journals 510 Niraparib outcomes in brca wild-type platinum sensitive recurrent ovarian cancer: a comparison of real-world data to the nova trial

2020 ◽  
Author(s):  
Douglas Cartwright ◽  
Patricia Roxburgh ◽  
Barbara Stanley ◽  
Jennifer Brown ◽  
Alistair Mclaren ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Real World ◽  
Recurrent Ovarian Cancer ◽  
Wild Type ◽  
Real World Data ◽  
World Data ◽  
Platinum Sensitive

Trabectedin Plus Pegylated Liposomal Doxorubicin in Recurrent Ovarian Cancer

2010 ◽  
Vol 28 (19) ◽  
pp. 3107-3114 ◽  
Author(s):  
Bradley J. Monk ◽  
Thomas J. Herzog ◽  
Stanley B. Kaye ◽  
Carolyn N. Krasner ◽  
Jan B. Vermorken ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Liposomal Doxorubicin ◽  
Performance Status ◽  
Pegylated Liposomal Doxorubicin ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Hazard Ratio ◽  
Platinum Sensitive ◽  
Platinum Based Chemotherapy ◽  
Hand Foot Syndrome

PurposeThe objective of this study was to compare the efficacy and safety of trabectedin plus pegylated liposomal doxorubicin (PLD) with that of PLD alone in women with recurrent ovarian cancer after failure of first-line, platinum-based chemotherapy.Patients and MethodsWomen ≥ 18 years, stratified by performance status (0 to 1 v 2) and platinum sensitivity, were randomly assigned to receive an intravenous infusion of PLD 30 mg/m2followed by a 3-hour infusion of trabectedin 1.1 mg/m2every 3 weeks or PLD 50 mg/m2every 4 weeks. The primary end point was progression-free survival (PFS) by independent radiology assessment.ResultsPatients (N = 672) were randomly assigned to trabectedin/PLD (n = 337) or PLD (n = 335). Median PFS was 7.3 months with trabectedin/PLD v 5.8 months with PLD (hazard ratio, 0.79; 95% CI, 0.65 to 0.96; P = .0190). For platinum-sensitive patients, median PFS was 9.2 months v 7.5 months, respectively (hazard ratio, 0.73; 95% CI, 0.56 to 0.95; P = .0170). Overall response rate (ORR) was 27.6% for trabectedin/PLD v 18.8% for PLD (P = .0080); for platinum-sensitive patients, it was 35.3% v 22.6% (P = .0042), respectively. ORR, PFS, and overall survival among platinum-resistant patients were not statistically different. Neutropenia was more common with trabectedin/PLD. Grade 3 to 4 transaminase elevations were also more common with the combination but were transient and noncumulative. Hand-foot syndrome and mucositis were less frequent with trabectedin/PLD than with PLD alone.ConclusionWhen combined with PLD, trabectedin improves PFS and ORR over PLD alone with acceptable tolerance in the second-line treatment of recurrent ovarian cancer.

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.

Should Bevacizumab Be Continued After Progression on Bevacizumab in Recurrent Ovarian Cancer?

2013 ◽  
Vol 23 (5) ◽  
pp. 833-838 ◽  
Author(s):  
Floor J. Backes ◽  
Debra L. Richardson ◽  
Georgia A. McCann ◽  
Blair Smith ◽  
Ritu Salani ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Bowel Perforation ◽  
Objective Response ◽  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
Response Rates ◽  
Recurrent Ovarian Cancer ◽  
Median Number ◽  
Cytotoxic Chemotherapy

ObjectiveThe optimal role of bevacizumab (Bev) in the treatment of ovarian cancer has not yet been established. Furthermore, it is unclear whether there is a benefit of Bev after progression on a Bev-containing regimen in ovarian cancer. The objective of this study was to compare response rates, progression-free survival (PFS), and overall survival between patients who were treated with chemotherapy and Bev after progression on Bev (BAB) versus patients who were treated with chemotherapy without Bev (CWOB).MethodsWe conducted a retrospective chart review of all patients who received treatment with Bev (with or without cytotoxic chemotherapy) for recurrent ovarian cancer at a single institution. Patients who received additional therapy after progression while on Bev were included.ResultsForty-six patients were included (16 CWOB group and 30 BAB). The median number of previous chemotherapy regimens was 2.5 for CWOB compared with 4 for BAB (P= 0.11). Fifty-two percent of patients had an objective response to the first Bev regimen before progressing on Bev. Response rates for the regimen after progression on Bev were 19% (3/16) in the CWOB group and 23% (7/30) in the BAB group (P= 1). Twenty-five percent of the patients who responded to the first Bev regimen and 18% of those who did not respond to the first Bev regimen responded to the second Bev regimen (P= 0.72). The median PFS for patients in the CWOB group was 2.6 months (95% confidence interval [CI], 1.3–5 months), compared with 5.0 months (95% CI, 3.5–7.3 months) for patients in the BAB group (P= 0.01). Overall survival was similar, 9.4 months (95% CI, 5.0–12.0 months) for CWOB versus 8.6 months (95% CI, 5.8–15.5 months) for BAB (P= 0.19). One patient in the BAB group died of a bowel perforation.ConclusionsIn patients previously treated with Bev for recurrent ovarian cancer, the subsequent addition of Bev to cytotoxic chemotherapy increased the PFS compared with patients not receiving a second course of Bev, but did so without an impact on overall survival. The response to the first Bev regimen did not predict whether a patient would respond again to the next Bev regimen. Randomized, larger studies will have to be performed to confirm this observation.

Overall survival results of ICON6: A trial of chemotherapy and cediranib in relapsed ovarian cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5506-5506 ◽  
Author(s):  
Jonathan A. Ledermann ◽  
Andrew C. Embleton ◽  
Timothy Perren ◽  
Gordon C. Jayson ◽  
Gordon J. S. Rustin ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Sample Size ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Primary Analysis ◽  
Logrank Test ◽  
Double Blind ◽  
Time To Death ◽  
Platinum Sensitive

5506 Background: ICON6 is a three-arm double-blind, placebo-controlled phase 3 trial of cediranib in platinum-sensitive relapsed ovarian cancer (NCT00532194). The primary analysis (Ledermann et al Lancet 2016) showed a significant (p < 0.0001), 2.3 month extension in progression-free survival (PFS) using cediranib with chemotherapy and as maintenance compared to chemotherapy and placebo. We present the final overall survival (OS) results. Methods: The trial was originally designed to recruit 2000 patients with OS as the primary endpoint. AstraZeneca discontinued cediranib development in Sep 2011, leading to an unplanned redesign prior to analysis. The sample size was reduced and primary outcome became PFS, comparing two arms, placebo (A) to cediranib given with chemotherapy and as maintenance (C). In arm B cediranib was given with chemotherapy followed by placebo maintenance. Analysis of PFS was performed on a sample size of 456 patients receiving a 20mg dose of cediranib. At the primary analysis, 52% patients had died; this mature OS analysis was performed after 85% patients died. Results: The OS analysis was performed at a median 25.6 months follow up; 102/118 (86%) died in A and 140/164 (85%) in C. In A the median survival was 19.9 months (95% CI: 17.4, 26.5) and in C 27.3 months (24.8, 33.0). Using the logrank test the Hazard Ratio estimate was 0.85 (0.66, 1.10) in favour of cediranib (p = 0.21). Evidence of non-proportionality of the survival curves was observed (p = 0.0029), so we measured the Restricted Mean Survival Time as an alternative to the median. Over 6 years, there was a 4.8 month (-0.1, 9.8) increase in time to death in C compared to A, from 29.4 to 34.2 months. The mean for arm B (32.0 months) was consistent with a benefit of increased use of cediranib. Conclusions: Cediranib has demonstrated a significant effect in increasing PFS. The mature survival analysis (85%) shows an improvement in median OS of 7.4 months, and an incremental benefit with increased cediranib use. The previously published significant PFS benefit coupled with the increase in OS highlights the potential value of cediranib in platinum-sensitive recurrent ovarian cancer. Further exploration of cediranib in this setting is underway. Clinical trial information: NCT00532194.

Apatinib as a salvage treatment in gynecologic cancer patients failed from two or more lines of prior chemotherapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e17009-e17009 ◽  
Author(s):  
Congying Xie ◽  
Meng Su ◽  
Xiance Jin
Keyword(s):  
Ovarian Cancer ◽  
Cervical Cancer ◽  
Cancer Patients ◽  
Gynecologic Cancer ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Recurrent Ovarian Cancer ◽  
Kaplan Meier ◽  
Hand Foot Syndrome

e17009 Background: The aim of this study was to evaluate the efficacy and safety of apatinib, an oral VEGFR2 inhibitor, in the treatment of advanced cervical and ovarian cancer patients who failed from two or more lines of chemotherapy. Methods: The advanced cervical and ovarian cancer patients, who experienced two or more lines of chemotherapy and treated with apatinib from April 2015 to January 2017, were retrospectively reviewed. All eligible patients received continuous apatinib treatment until disease progression, death, or intolerable toxicity. Survival and toxicities outcome were evaluated by Kaplan-Meier method and according to NCI-CTC4.0. Results: Twenty-six patients were eligible (cervical cancer:12 and ovarian cancer:14). After dose adjustment, 14 patients (53.8%) received 500 mg daily of apatinib, 8 patients received 250mg, 3 received 425mg and 1 received 675mg daily. The median progression-free survival (PFS) of cervical cancer and ovarian cancer were 8 months (95%CI:3.83-12.17) and 4 months (95%CI:1.57-6.44), respectively. Objective response rates in cervical cancer and ovarian cancer were 50% and 50%, respectively. Disease control rates were 100% for cervical cancer and 71.4% for ovarian cancer. Complete response was not observed in either cervical cancer or ovarian cancer. A 52-year old patient with recurrent ovarian cancer, experienced two lines of chemotherapy failure, was orally administered with apatinib at a dose of 250mg daily from November 2015, got partial response (PR) after one month, PFS have not yet reach. A 43-year old female patient with advanced cervical cancer, experienced three lines of chemotherapy failure, was orally administered with apatinib at a dose of 250mg daily from September 2015, got PR with a PFS of 14 months. The toxicities associated with apatinib treatment was generally acceptable with 8 patients developed grade 3/4 toxicity. The most common adverse events in this study were hypertension(n = 17), hand-foot syndrome(n = 24), and mouth mucositis(n = 20). Conclusions: Apatinib monotherapy showed promising efficiency with tolerable toxicity for advanced/recurrent cervical and ovarian cancer patients who failed from two or more lines of chemotherapy.

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