Efficacy of Trabectedin in Platinum-Sensitive-Relapsed Ovarian Cancer: New Data From the Randomized OVA-301 Study

2011 ◽  
Vol 21 (Supp 1) ◽  
pp. S12-S16 ◽  
Author(s):  
Nicoletta Colombo
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Combined Treatment ◽  
Advanced Ovarian Cancer ◽  
Pegylated Liposomal Doxorubicin ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Positive Effects ◽  
Platinum Sensitive ◽  
Third Line

The results of the OVA-301 study show that trabectedin in combination with pegylated liposomal doxorubicin (PLD) results in improved progression-free survival and response rate in patients with advanced ovarian cancer. The trial has also demonstrated a trend toward improvement in overall survival. A subgroup analysis indicates that in the subset of patients with platinum-free interval (PFI) of 6 to 12 months, the combined treatment resulted in a 6-month improvement in overall survival. Furthermore, in the patients who have received third-line treatment with a platinum agent, it was found that the survival was better in those who had received trabectedin and PLD. These results suggest that prolonging the PFI by a nonplatinum-effective regimen improves the outcome with subsequent, third-line platinum treatment. This strategy may also have positive effects in treatment tolerability, as it allows extra time to recover from platinum-induced toxicities. This hypothesis is currently been tested in the INOVATYON (INternational OVArian Cancer Patients Trial With YONdelis) phase III study.

scholarly journals Pegylated Liposomal Doxorubicin and Carboplatin Compared With Paclitaxel and Carboplatin for Patients With Platinum-Sensitive Ovarian Cancer in Late Relapse

2010 ◽  
Vol 28 (20) ◽  
pp. 3323-3329 ◽  
Author(s):  
Eric Pujade-Lauraine ◽  
Uwe Wagner ◽  
Elisabeth Aavall-Lundqvist ◽  
Val Gebski ◽  
Mark Heywood ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Survival Data ◽  
Liposomal Doxorubicin ◽  
Pegylated Liposomal Doxorubicin ◽  
Sensory Neuropathy ◽  
Recurrent Ovarian Cancer ◽  
Phase Iii ◽  
Late Relapse ◽  
Platinum Sensitive

PurposeThis randomized, multicenter, phase III noninferiority trial was designed to test the efficacy and safety of the combination of pegylated liposomal doxorubicin (PLD) with carboplatin (CD) compared with standard carboplatin and paclitaxel (CP) in patients with platinum-sensitive relapsed/recurrent ovarian cancer (ROC).Patients and MethodsPatients with histologically proven ovarian cancer with recurrence more than 6 months after first- or second-line platinum and taxane-based therapies were randomly assigned by stratified blocks to CD (carboplatin area under the curve [AUC] 5 plus PLD 30 mg/m2) every 4 weeks or CP (carboplatin AUC 5 plus paclitaxel 175 mg/m2) every 3 weeks for at least 6 cycles. Primary end point was progression-free survival (PFS); secondary end points were toxicity, quality of life, and overall survival.ResultsOverall 976 patients were recruited. With median follow-up of 22 months, PFS for the CD arm was statistically superior to the CP arm (hazard ratio, 0.821; 95% CI, 0.72 to 0.94; P = .005); median PFS was 11.3 versus 9.4 months, respectively. Although overall survival data are immature for final analysis, we report here a total of 334 deaths. Overall severe nonhematologic toxicity (36.8% v 28.4%; P < .01) leading to early discontinuation (15% v 6%; P < .001) occurred more frequently in the CP arm. More frequent grade 2 or greater alopecia (83.6% v 7%), hypersensitivity reactions (18.8% v 5.6%), and sensory neuropathy (26.9% v 4.9%) were observed in the CP arm; more hand-foot syndrome (grade 2 to 3, 12.0% v 2.2%), nausea (35.2% v 24.2%), and mucositis (grade 2-3, 13.9% v 7%) in the CD arm.ConclusionTo our knowledge, this trial is the largest in recurrent ovarian cancer and has demonstrated superiority in PFS and better therapeutic index of CD over standard CP.

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.

Randomized Phase III Trial of Gemcitabine Compared With Pegylated Liposomal Doxorubicin in Patients With Platinum-Resistant Ovarian Cancer

2007 ◽  
Vol 25 (19) ◽  
pp. 2811-2818 ◽  
Author(s):  
David G. Mutch ◽  
Mauro Orlando ◽  
Tiana Goss ◽  
Michael G. Teneriello ◽  
Alan N. Gordon ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Liposomal Doxorubicin ◽  
Single Agent ◽  
Pegylated Liposomal Doxorubicin ◽  
Progression Free Survival ◽  
Therapeutic Index ◽  
Phase Iii ◽  
End Points ◽  
Platinum Resistant ◽  
Significant Difference

Purpose Ovarian cancer (OC) patients experiencing progressive disease (PD) within 6 months of platinum-based therapy in the primary setting are considered platinum resistant (Pt-R). Currently, pegylated liposomal doxorubicin (PLD) is a standard of care for treatment of recurrent Pt-R disease. On the basis of promising phase II results, gemcitabine was compared with PLD for efficacy and safety in taxane-pretreated Pt-R OC patients. Patients and Methods Patients (n = 195) with Pt-R OC were randomly assigned to either gemcitabine 1,000 mg/m2 (days 1 and 8; every 21 days) or PLD 50 mg/m2 (day 1; every 28 days) until PD or undue toxicity. Optional cross-over therapy was allowed at PD or at withdrawal because of toxicity. Primary end point was progression-free survival (PFS). Additional end points included tumor response, time to treatment failure, survival, and quality of life. Results In the gemcitabine and PLD groups, median PFS was 3.6 v 3.1 months; median overall survival was 12.7 v 13.5 months; overall response rate (ORR) was 6.1% v 8.3%; and in the subset of patients with measurable disease, ORR was 9.2% v 11.7%, respectively. None of the efficacy end points showed a statistically significant difference between treatment groups. The PLD group experienced significantly more hand-foot syndrome and mucositis; the gemcitabine group experienced significantly more constipation, nausea/vomiting, fatigue, and neutropenia but not febrile neutropenia. Conclusion Although this was not designed as an equivalency study, gemcitabine and PLD seem to have a comparable therapeutic index in this population of Pt-R taxane-pretreated OC patients. Single-agent gemcitabine may be an acceptable alternative to PLD for patients with Pt-R OC.

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