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.
Phase II Clinical Trial of Pegylated Liposomal Doxorubicin (JNS002) in Japanese Patients with Mullerian Carcinoma (Epithelial Ovarian Carcinoma, Primary Carcinoma of Fallopian Tube, Peritoneal Carcinoma) Having a Therapeutic History of Platinum-based Chemotherapy: A Phase II Study of the Japanese Gynecologic Oncology Group
