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: 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.

Overall Survival Results of the Feasibility Study of Adjuvant Chemotherapy With Docetaxel Plus Cisplatin Followed by Long-term Single-agent Administration of S-1 in Patients With Completely Resected Non-Small Cell Lung Cancer: Thoracic Oncology Research Group (TORG) 0809.

OBJECTIVES: The TORG0809 study was a multicenter feasibility study of long-term single-agent therapy with S-1 after docetaxel plus cisplatin therapy in patients with completely resected stage II or stage IIIA non-small cell lung cancer. We report the results of the final overall survival (OS) analysis. PATIENTS AND METHODS: A total of 129 eligible patients received 3 cycles of docetaxel (60 mg/m, day 1) plus cisplatin (80 mg/m, day 1), followed by S-1 at 40 mg/m twice daily for 14 consecutive days, for >6 months (maximum, 1 y). RESULTS: At the cutoff date of April 13, 2016, the median follow-up time was 6.0 years. Of the 129 patients, 43 had died, and 74 patients developed disease recurrence or died. The median OS had not been reached. The 5-year OS rate was 71% [95% confidence interval (CI), 62-78]. The 5-year OS rates in the patients with stage II and stage IIIA were 76% and 68%, respectively. The median recurrence-free survival (RFS) duration was 3.4 years (95% CI, 2.3-5.7). The 5-year RFS rate was 44% (95% CI, 36-53). The 5-year RFS rates in patients with stage II and stage IIIA disease were 57% and 38%, respectively. Disease recurrence occurred in 68 patients, and 62 of these patients received second-line chemotherapy. The most common sites of recurrence were the brain (n=22) and mediastinal lymph nodes (n=22). CONCLUSION: The survival data obtained from this study are promising and comparable to those reported from a previous study conducted in Japan.