Chemotherapy-induced neutropenia as a biomarker of survival in advanced ovarian carcinoma: an exploratory study of the gynecologic oncology group.

ABSTRACT

OBJECTIVE: To determine whether chemotherapy-induced neutropenia (C-iN) is associated with improved survival in a population of primary advanced ovarian cancer and peritoneal carcinoma patients treated with a carboplatin plus paclitaxel chemotherapy backbone. METHODS: A post-hoc exploratory analysis of Gynecologic Oncology Group (GOG) protocol 182 was performed. Landmark analysis was conducted on all patients with progression-free survival >18weeks from the time of study entry. Neutropenia was defined as the absolute neutrophil count <1000mm(3). The occurrence of C-iN was analyzed according to demographic, clinicopathologic, and therapeutic intent, including age, body surface area, and treatment arm. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. The Cox proportional hazards model was used to evaluate independent prognostic factors and to estimate their effects on PFS and OS. RESULTS: Neutropenic data was available for 3447 patients. Neutropenic (n=3196) and non-neutropenic groups (n=251) were similar in demographic and clinicopathologic characteristics. Neutropenic patients experienced significantly improved survival compared to non-neutropenic patients with the adjusted hazard ratio (HR) for death being 0.86 (95% confidence interval 0.74-0.99; p=0.041). There was no survival benefit associated with any of the treatment arms among patients with C-iN. CONCLUSION: These data suggest that C-iN may represent a clinical biomarker associated with a survival advantage for patients with untreated advanced ovarian cancer. The absence of C-iN may indicate under-dosing and ultimately attenuated anti-neoplastic effect in vulnerable populations.