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
- Author:
Takashi MOTOHASHI
1
;
Akira YABUNO
;
Hiroshi MICHIMAE
;
Tetsuro OHISHI
;
Miwa NONAKA
;
Masashi TAKANO
;
Shin NISHIO
;
Hiroyuki FUJIWARA
;
Keiichi KEIICHI
;
Eiji KONDO
;
Toru SUGIYAMA
;
Tsutomu TABATA
Author Information
- Publication Type:Original Article
- From:Journal of Gynecologic Oncology 2021;32(1):e9-
- CountryRepublic of Korea
- Language:English
-
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 progressionfree 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.
