Randomized phase III trial comparing pegylated liposomal doxorubicin (PLD) 50 mg/m2 and 40 mg/m2 in patients with platinum-resistant Müllerian carcinoma (JGOG3018).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5550-5550
Author(s):  
Akira Yabuno ◽  
Tsutomu Tabata ◽  
Hirofumi Michimae ◽  
Tetsuro Oishi ◽  
Miwa Nonaka ◽  
...  
Keyword(s):  
Liposomal Doxorubicin ◽  
Standard Dose ◽  
Performance Status ◽  
Single Agent ◽  
Pegylated Liposomal Doxorubicin ◽  
Phase Iii ◽  
Skin Reactions ◽  
Platinum Resistant ◽  
Number Of Patients ◽  
Müllerian Carcinoma

5550 Background: The standard dose of single-agent pegylated liposomal doxorubicin (PLD) is 50 mg/m2 every 4 weeks, but 40 mg/m2 has recently been used in clinical practice, though there is no evidence available to support its use. Methods: A Phase III, randomized, multicenter, non-inferiority study comparing progression-free survival (PFS) of patients with platinum-resistant Mullerian carcinoma (epithelial ovarian, fallopian tube, or primary peritoneal carcinoma) treated with an experimental arm (40 mg/m2 PLD) versus a standard arm (50 mg/m2 PLD) until 10 courses, disease progression, or unacceptable toxicity was conducted. Eligible patients had ≤ 2 prior lines. Stratification was by performance status (PS) and PFS of prior chemotherapy (<3 months versus ≥3 months). The primary endpoint was PFS, and secondary endpoints were overall survival (OS), toxicity profile, clinical response, and tolerability. The target total number of patients was 412. Results: The trial was closed due to accrual futility as patient recruitment was slow , with 272 patients randomized to the experimental arm (n=137) and the standard arm (n=135). The final analysis was performed with 234 deaths and 269 events for PFS. Median patient age was 62 years; 58% of patients had a treatment-free interval less than 3 months, and 81% of patients had PS 0. In the experimental versus standard arm, median PFS was 4.0 months versus 4.0 months (HR 1.065, 95.8%CI: 0.830-1.366), and median OS was 14.0 months versus 14.0 months (HR 1.078, 95%CI: 0.831-1.397). Adverse events ≥Grade 2 including oral cavity mucositis were more frequent in the standard arm than in the experimental arm (26.7% vs. 13.5%, respectively; p=0.0089), but there was no difference in ≥Grade 2 hand-foot-skin reactions (19.8% vs. 15.0%, respectively; p=0.333). Conclusions: The non-inferiority of PFS with the reduced dosing schedule was not confirmed because the trial was closed prematurely, but PFS and OS were similar. These results suggest a reduction of the standard dose of PLD because of the low rate of oral mucositis in patients with platinum-resistant ovarian cancer treated with the lower dose regimen. Clinical trial information: UMIN000003130.

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.

A randomized double-blind phase III trial comparing vintafolide plus pegylated liposomal doxorubicin (PLD) versus PLD plus placebo in patients with platinum-resistant ovarian cancer (PROCEED).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS5613-TPS5613 ◽  
Author(s):  
R. Wendel Naumann ◽  
Lucy Gilbert ◽  
Anthonette M. Miller ◽  
Hong Ma ◽  
Sharad A. Ghamande ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Disease Progression ◽  
Folate Receptor ◽  
Performance Status ◽  
Pegylated Liposomal Doxorubicin ◽  
Phase Iii ◽  
Ecog Performance Status ◽  
Double Blind ◽  
Platinum Resistant ◽  
Platinum Based Chemotherapy

TPS5613 Background: Folate receptor (FR) is expressed on the majority of epithelial ovarian cancers and FR expression appears to be a negative prognostic factor in this setting. Vintafolide (EC145) is a folate-conjugate designed to selectively deliver desacetylvinblastine monohydrazide (DAVLBH) to FR-expressing cells. 99mTc-Etarfolatide (EC20) is a technetium-labeled folate that identifies FR-expressing tumors. In a phase 2 study comparing vintafolide + PLD with PLD alone, the combination demonstrated a statistically and clinically significant delay in PFS (5.0 months) compared with PLD alone (2.7 months) in women with platinum-resistant ovarian cancer (Naumann et al, ASCO 2011). Data also indicated that 99mTc-etarfolatide may have utility for selecting patients most likely to benefit from vintafolide therapy. Methods: This is an international, randomized, double-blind, placebo-controlled phase 3 study of PLD ± vintafolide therapy compared in patients with primary or secondary platinum-resistant ovarian cancer (NCT01170650). Key eligibility criteria include: ≥18 years, pathology-confirmed epithelial ovarian, fallopian tube or primary peritoneal carcinoma, prior platinum-based chemotherapy, a RECIST v1.1 measureable lesion, and ECOG performance status 0 or 1. At baseline, patients undergo 99mTc-Etarfolatide imaging to identify FR-positive lesions and are subsequently randomized to the vintafolide ± PLD. PLD (50 mg/m2) adjusted for Ideal Body weight is administered on day 1 of a 4-week cycle and treatment continues until the maximum allowable cumulative dose (550 mg/m2) is reached or until disease progression or intolerable toxicity. Vintafolide (2.5 mg) or placebo is administered on days 1, 3, 5, 15, 17, and 19 of a 4-week cycle and treatment can continue for up to 20 cycles or until unacceptable toxicity or disease progression. The primary objective is to assess PFS based on investigator assessment (RECIST v1.1) in FR positive patients. Secondary objectives include OS, safety/tolerability, overall response rate, and disease control rate. Enrollment to the study is currently ongoing. Clinical trial information: NCT01170650.

AGO-OVAR 2.29 (ENGOT-ov34): Atezolizumab in combination with bevacizumab and chemotherapy versus bevacizumab and chemotherapy in recurrent ovarian cancer (ROC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS5601-TPS5601 ◽  
Author(s):  
Frederik Marme ◽  
Patricia Pautier ◽  
Els Van Nieuwenhuysen ◽  
Alexander Reuss ◽  
Andres Redondo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Liposomal Doxorubicin ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Pegylated Liposomal Doxorubicin ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Tumor Biopsy ◽  
Peritoneal Cancer ◽  
Platinum Based Chemotherapy

TPS5601 Background: A standard non-platinum based treatment option in patients with relapsed ovarian cancer is bevacizumab in combination with paclitaxel or pegylated liposomal doxorubicin, but responses are still short-lived. Checkpoint-inhibitors as single agent have limited activity in ovarian cancer. However, the role of the checkpoint-inhibitor like atezolizumab, in addition to chemotherapy and bevacizumab in ovarian cancer is so far undefined. Methods: AGO-OVAR 2.29 is a randomized (1:1), double blinded, phase III trial evaluating the efficacy and safety of atezolizumab plus bevacizumab and chemotherapy (weekly paclitaxel or pegylated liposomal doxorubicin) compared with placebo plus bevacizumab and chemotherapy in patients with recurrent ovarian-, fallopian tube, or primary peritoneal cancer with 1st or 2nd relapse within 6 months after platinum-based chemotherapy or 3rd relapse. A tumor biopsy available at study entry for PD-L1 testing is mandatory. Patients are treated with chemotherapy plus bevacizumab +/- atezolizumab/placebo until progression or prohibitive toxicity. Co-primary endpoints are overall survival and progression-free survival. It is planned to randomize 664 patients. A safety interim analysis will be done when 24 patients have been randomized and completed at least cycle 1. As of 1st February 2019, 24 patients have been randomized. Clinical trial information: NCT03353831.

Health-related quality of life (HRQoL) results from the AURELIA trial evaluating bevacizumab (BEV) plus chemotherapy (CT) for platinum-resistant recurrent ovarian cancer (OC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5542-5542 ◽  
Author(s):  
Martin R. Stockler ◽  
Felix Hilpert ◽  
Michael Friedlander ◽  
Madeleine King ◽  
Lari B. Wenzel ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Repeated Measures ◽  
Single Agent ◽  
Pegylated Liposomal Doxorubicin ◽  
Phase Iii ◽  
Symptom Improvement ◽  
Baseline Score ◽  
Platinum Resistant ◽  
Gi Symptoms ◽  
Patient Reported

5542 Background: Adding BEV to CT significantly improved PFS in platinum-resistant OC in the open-label phase III AURELIA trial. As symptom improvement is a major goal of treatment, determining effects on HRQoL was a key secondary aim of AURELIA. Methods: After investigator selection of single-agent CT (pegylated liposomal doxorubicin, topotecan, or weekly paclitaxel), patients (pts) with measurable/assessable platinum-resistant OC were randomized to CT ± BEV. HRQoL and symptoms were assessed at baseline and every 2 or 3 cycles (8/9 wks) until PD using the EORTC OC Module (OV28) and FOSI. The primary HRQoL endpoint was an absolute improvement of ≥15% (≥15 points) on the 100-point OV28 subscale for abdominal (abdo)/GI symptoms (items 1–6) at wk 8/9. Pts with missing questionnaires (Qs) were included and considered not to have improved. A sensitivity analysis excluded pts with Qs missing for reasons other than PD/death or switch from CT to BEV. Subgroup analyses of symptomatic pts included only those with a baseline score ≥15 (sufficient to show ≥15-point improvement). Mixed-model repeated measures (MMRM) analysis was used to compare Qs from all time points until PD/death, not just wk 8/9. The FOSI was analyzed similarly. Results: Baseline Qs were available from 89% of 361 randomized pts. At wk 8/9, 81% of BEV–CT vs 68% of CT pts who were alive and PD-free returned OV28 Qs. For the primary HRQoL endpoint, more BEV–CT than CT pts had a ≥15% improvement in the OV28 abdo/GI symptom subscale at wk 8/9 (21.9% vs 9.3%, 12.7% difference [95% CI 4.4–20.9]; p = 0.002). The sensitivity analysis described above showed a 13.3% difference [95% CI 4.5–22.1]. In the subgroup of 233 pts with a baseline score ≥15, there was a 16.9% difference (95% CI 6.1–27.6) favoring BEV–CT (29.6% vs 12.7%). MMRM analysis of OV28 abdo/GI symptom subscale scores also favored BEV–CT (6.4-point difference [95% CI 1.28–11.6]). More BEV–CT than CT pts had a ≥15% improvement in FOSI score at wk 8/9 (12.2% vs 3.1%, 9.0% difference [95% CI 2.9–15.2]). Conclusions: Adding BEV to CT resulted in more frequent ≥15% improvements in patient-reported abdo/GI symptoms in platinum-resistant OC. Clinical trial information: NCT00976911.

scholarly journals Olaparib Versus Nonplatinum Chemotherapy in Patients With Platinum-Sensitive Relapsed Ovarian Cancer and a Germline BRCA1/2 Mutation (SOLO3): A Randomized Phase III Trial

2020 ◽  
Vol 38 (11) ◽  
pp. 1164-1174 ◽  
Author(s):  
Richard T. Penson ◽  
Ricardo Villalobos Valencia ◽  
David Cibula ◽  
Nicoletta Colombo ◽  
Charles A. Leath ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Liposomal Doxorubicin ◽  
Single Agent ◽  
Pegylated Liposomal Doxorubicin ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
End Point ◽  
Platinum Sensitive ◽  
Platinum Based Chemotherapy ◽  
Measurable Disease

PURPOSE A phase II study (ClinicalTrials.gov identifier: NCT00628251 ) showed activity of olaparib capsules versus pegylated liposomal doxorubicin in patients with germline BRCA-mutated platinum-resistant or partially platinum-sensitive relapsed ovarian cancer. We conducted a phase III trial (SOLO3) of olaparib tablets versus nonplatinum chemotherapy in patients with germline BRCA-mutated platinum-sensitive relapsed ovarian cancer who had received at least 2 prior lines of platinum-based chemotherapy. PATIENTS AND METHODS In this randomized, open-label trial, patients were randomly assigned 2:1 to olaparib 300 mg twice a day or physician’s choice single-agent nonplatinum chemotherapy (pegylated liposomal doxorubicin, paclitaxel, gemcitabine, or topotecan). The primary end point was objective response rate (ORR) in the measurable disease analysis set assessed by blinded independent central review (BICR). The key secondary end point was progression-free survival (PFS) assessed by BICR in the intent-to-treat population. RESULTS Of 266 randomly assigned patients, 178 were assigned to olaparib and 88 to chemotherapy. In patients with measurable disease (olaparib, n = 151; chemotherapy, n = 72), the BICR-assessed ORR was significantly higher with olaparib than with chemotherapy (72.2% v 51.4%; odds ratio [OR], 2.53 [95% CI, 1.40 to 4.58]; P = .002). In the subgroup who had received 2 prior lines of treatment, the ORR was 84.6% with olaparib and 61.5% with chemotherapy (OR, 3.44 [95% CI, 1.42 to 8.54]). BICR-assessed PFS also significantly favored olaparib versus chemotherapy (hazard ratio, 0.62 [95% CI, 0.43 to 0.91]; P = .013; median, 13.4 v 9.2 months). Adverse events were consistent with the established safety profiles of olaparib and chemotherapy. CONCLUSION Olaparib resulted in statistically significant and clinically relevant improvements in ORR and PFS compared with nonplatinum chemotherapy in patients with germline BRCA-mutated platinum-sensitive relapsed ovarian cancer who had received at least 2 prior lines of platinum-based chemotherapy.

Interim safety analysis of the randomized phase III PELICAN trial evaluating pegylated liposomal doxorubicin (PLD) versus capecitabine as first-line therapy for metastatic breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1118-1118
Author(s):  
S. Al-Batran ◽  
S. Saupe ◽  
M. Schmidt ◽  
R. Kreienberg ◽  
B. Otremba ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Disease Progression ◽  
Performance Status ◽  
Single Agent ◽  
Metastatic Breast ◽  
Pegylated Liposomal Doxorubicin ◽  
Phase Iii ◽  
First Line ◽  
Grade 3

1118 Background: Treatment of metastatic breast cancer (MBC) focuses on relieving symptoms and extending life. Single-agent therapy is preferred in the first-line setting to reduce the risk of toxicity and maintain quality of life. The PELICAN trial was designed to evaluate efficacy and safety of first-line PLD vs capecitabine at standard approved dosages. Methods: PELICAN is an open-label, multinational, randomized, multicenter trial. MBC Patients (pts) were randomized to receive PLD (50 mg/m2 every 28 days) or capecitabine (1250 mg/m2 BID x 14 days every 21 days) until disease progression or unacceptable toxicity. The primary endpoint was to compare time to disease progression between treatment arms. Toxicity was evaluated continuously. Results: The study is still ongoing, but no longer recruiting. So far, 210 pts (PLD, 105; capecitabine, 105) were evaluated for safety, of whom 131 pts have already completed their treatment (83 for disease progression, 19 for toxicity, 5 died, 24 for other reasons). 90% of pts had ECOG performance status 1 or 2, and 79% were postmenopausal. Mean age was 61.5 years, and 34% received prior adjuvant anthracycline. Pts received a median of 4 cycles of PLD and a median of 5 cycles of capecitabine. Over 90% of pts in both groups experienced at least one adverse event (AE). Grade 3/4 AEs were reported in 99 patients (PLD, 44; capecitabine, 55). Hand foot syndrome (HFS) was the most common AE (grade 3: PLD 35%; capecitabine 19%), followed by diarrhea (grade 3/4: PLD, 0; capecitabine, 13%) and thromboembolic events (PLD, 0%; capecitabine, 9%). Other grade 3/4 AEs affected 1 week in 16%. Conclusions: Overall, first-line monotherapy with PLD or capecitabine at approved doses was maintainable for a median of about 4 months with manageable AEs. Interim safety results of the PELICAN trial show no unanticipated toxicity. Efficacy results will be available once all patients have completed their therapy. [Table: see text]

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