Dataset Information

Randomized phase III trial comparing pegylated liposomal doxorubicin (PLD) at 50 mg/m² versus 40 mg/m² in patients with platinum-refractory and -resistant ovarian carcinoma: the JGOG 3018 Trial.

ABSTRACT:

Objective

The standard dose for pegylated liposomal doxorubicin (PLD) is 50 mg/m² every 4 weeks. While 40 mg/m² has recently been used in clinical practice, evidence supporting this use remains lacking.

Methods

This phase III randomized, non-inferiority study compared progression-free survival (PFS) for patients with platinum-resistant ovarian carcinoma between an experimental arm (40 mg/m² PLD) and a standard arm (50 mg/m² PLD) until 10 courses, disease progression or unacceptable toxicity. Eligible patients had received ?2 prior lines. Stratification was by performance status 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 total number of patients was 470.

Results

The trial was prematurely closed due to slow recruitment, with 272 patients randomized to the experimental arm (n=137) and standard arm (n=135). Final analysis was performed with 234 deaths and 269 events for PFS. In the experimental arm vs. standard arm, median PFS was 4.0 months vs. 4.0 months (hazard ratio [HR]=1.065; 95% confidence interval [CI]=0.830-1.366) and median OS was 14.0 months vs. 14.0 months (HR=1.078; 95% CI=0.831-1.397). Hematologic toxicity and oral cavity mucositis (?grade 2) were more frequent in the standard arm than in the experimental arm, but no difference was seen in ?grade 2 hand-foot skin reaction.

Conclusion

Non-inferiority of 2 PLD dosing schedule was not confirmed because the trial was closed prematurely. However, recommendation of dose reduction of PLD should be based both on efficacy and safety.

Trial registration

UMIN Clinical Trials Registry Identifier: UMIN000003130.

SUBMITTER: Motohashi T

PROVIDER: S-EPMC7767649 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Randomized phase III trial comparing pegylated liposomal doxorubicin (PLD) at 50 mg/m² versus 40 mg/m² in patients with platinum-refractory and -resistant ovarian carcinoma: the JGOG 3018 Trial.

Motohashi Takashi T Yabuno Akira A Michimae Hiroshi H Ohishi Tetsuro T Nonaka Miwa M Takano Masashi M Nishio Shin S Fujiwara Hiroyuki H Fujiwara Keiichi K Kondo Eiji E Sugiyama Toru T Tabata Tsutomu T

Journal of gynecologic oncology 20201110 1

<h4>Objective</h4>The standard dose for pegylated liposomal doxorubicin (PLD) is 50 mg/m² every 4 weeks. While 40 mg/m² has recently been used in clinical practice, evidence supporting this use remains lacking.<h4>Methods</h4>This phase III randomized, non-inferiority study compared progression-free survival (PFS) for patients with platinum-resistant ovarian carcinoma between an experimental arm (40 mg/m² PLD) and a standard arm (50 mg/m² PLD) until 10 courses, disease progression or unacceptabl ...[more]

PMID: 33185050

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Project description:PurposeThe noninterventional, prospective NIMES-ROC phase IV study (NCT02825420) evaluated trabectedin plus pegylated liposomal doxorubicin (PLD) in real-life clinical practice.Patients and methodsEligible participants included adults with platinum-sensitive recurrent ovarian cancer (PS-ROC) who had received one or more cycles of trabectedin/PLD before inclusion according to the marketing authorization. The primary endpoint was progression-free survival (PFS) according to investigator criteria.ResultsTwo hundred eighteen patients from five European countries were evaluated, 72.5% of whom were pretreated with at least two prior chemotherapy lines and received a median of six cycles of trabectedin/PLD (range: 1-24). Median PFS was 9.46 months (95% confidence interval [CI], 7.9-10.9), and median overall survival (OS) was 23.56 months (95% CI, 18.1-34.1). Patients not pretreated with an antiangiogenic drug obtained larger median PFS (p < .007) and OS (p < .048), largely owning to differences between the two populations. Twenty-four patients (11.0%) had a complete response, and 57 patients (26.1%) achieved a partial response for an objective response rate (ORR) of 37.2%. Fifty-nine patients (27.1%) had disease stabilization for a disease control rate of 64.2%. No statistically significant difference in PFS, OS, or ORR was observed by BRCA1/2 status and platinum sensitivity. Most common grade 3/4 adverse events (AEs) were neutropenia (30.3%), anemia (6.4%), thrombocytopenia (5.5%), and asthenia (5.0%). No deaths attributed to treatment-related AEs or unexpected AEs occurred.ConclusionThe combination of trabectedin/PLD represents a clinically meaningful and safe option for patients with PS-ROC regardless of prior treatment with an antiangiogenic drug, being comparable with previously observed outcomes in selected and less pretreated patients from clinical trials.Implications for practiceThis noninterventional, prospective study, conducted in 57 reference sites across Europe, consistently confirmed that trabectedin plus pegylated liposomal doxorubicin (PLD) in routine clinical practice represents a clinically meaningful and safe option for women with platinum-sensitive recurrent ovarian cancer. Although the study population represented a heterogeneous, older, and more pretreated population than those in prospective clinical trials, the combination of trabectedin plus PLD induced comparable clinical benefits, with a similar and manageable safety profile. Overall, these findings show that trabectedin in combination with PLD maintains antitumor activity when administered to heavily pretreated patients in real-life clinical practice.

Project description:BACKGROUND:Olaratumab is a platelet-derived growth factor receptor-? (PDGFR?)-targeting monoclonal antibody blocking PDGFR? signaling. PDGFR? expression is associated with a more aggressive phenotype and poor ovarian cancer outcomes. This randomized, open label phase II study evaluated olaratumab plus liposomal doxorubicin compared with liposomal doxorubicin alone in advanced ovarian cancer patients. METHODS:Patients with platinum-refractory or platinum-resistant advanced ovarian cancer were randomized 1:1 to receive liposomal doxorubicin (40?mg/m2, intravenous infusion) administered every 4?weeks with or without olaratumab (20?mg/kg, IV infusion) every 2?weeks. Patients were stratified based on prior response to platinum therapy (refractory vs resistant). The primary efficacy endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate, duration of response, and safety. RESULTS:A total of 123 patients were treated (62 olaratumab+liposomal doxorubicin; 61 liposomal doxorubicin). Median PFS was 4.2?months for olaratumab+liposomal doxorubicin and 4.0?months for liposomal doxorubicin (stratified hazard ratio [HR]?=?1.043; 95% confidence interval [CI] 0.698-1.558; p?=?0.837). Median OS was 16.6?months and 16.2?months in the olaratumab+liposomal doxorubicin and liposomal doxorubicin arms, respectively (HR?=?1.098; 95% CI 0.71-1.71). In the platinum-refractory subgroup, median PFS was 5.5?months (95% CI 1.6-9.2) and 3.7?months (95% CI 1.9-9.2) in the olaratumab+liposomal doxorubicin (n?=?15) and liposomal doxorubicin arms (n?=?16), respectively (HR?=?0.85; 95% CI 0.38-1.91). Overall, 59.7% (olaratumab+liposomal doxorubicin) and 65.6% (liposomal doxorubicin) of patients reported grade???3 adverse events regardless of causality. The most common treatment-emergent adverse events (all grades) regardless of causality were fatigue related (61%), nausea (57%), and constipation (52%) with olaratumab+liposomal doxorubicin and nausea (64%), fatigue related (62%), and mucositis (46%) with liposomal doxorubicin. CONCLUSIONS:The addition of olaratumab to liposomal doxorubicin did not result in significant prolongation of PFS or OS in platinum-resistant or platinum-refractory ovarian cancer. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT00913835 ; registered June 2, 2009.

Dataset Information

Randomized phase III trial comparing pegylated liposomal doxorubicin (PLD) at 50 mg/m² versus 40 mg/m² in patients with platinum-refractory and -resistant ovarian carcinoma: the JGOG 3018 Trial.

Objective

Methods

Results

Conclusion

Trial registration

Publications

Randomized phase III trial comparing pegylated liposomal doxorubicin (PLD) at 50 mg/m² versus 40 mg/m² in patients with platinum-refractory and -resistant ovarian carcinoma: the JGOG 3018 Trial.

Similar Datasets

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