Heterogeneous treatment effect of dose‐dense paclitaxel plus carboplatin therapy for advanced ovarian cancer

Abstract

AbstractA Japanese clinical trial (JGOG3016) showed that dose‐dense weekly paclitaxel in combination with carboplatin extensively prolonged overall survival (OS) in patients with advanced ovarian cancer. However, in other clinical trials, dose‐dense paclitaxel regimens were not superior to triweekly paclitaxel regimens. In this study, causal tree analysis was applied to explore subpopulations with different treatment effects of dose‐dense paclitaxel in a data‐driven approach. The 587 participants with stage II–IV ovarian cancer in the JGOG3016 trial were used for model development. The primary endpoint was treatment effect in terms of 3‐year OS in patients receiving dose‐dense vs. conventional paclitaxel therapies. In patients <50 years, the 3‐year OS was similar in both groups; however, it was higher in the dose‐dense group in patients ≥50 years. Dose‐dense paclitaxel showed strong positive treatment effects in patients ≥50 years with stage II/III disease, BMI <23 kg/m2, non‐CC/MC, and residual tumor ≥1 cm. In contrast, although there was no significant difference in OS; the 3‐year OS rate was 23% lower in dose‐dense paclitaxel than conventional paclitaxel in patients ≥60 years with stage IV cancer. Patients in this group had a particularly lower performance status than other groups. Our causal tree analysis suggested that poor prognosis groups represented by residual tumor tissue ≥1 cm benefit from dose‐dense paclitaxel, whereas elderly patients with advanced disease and low‐performance status are negatively impacted by dose‐dense paclitaxel. These subpopulations will be of interest to future validation studies. Personalized treatments based on clinical features are expected to improve advanced ovarian cancer prognosis.