Chemotherapy-induced neutropenia as a biomarker of survival in advanced ovarian carcinoma: An exploratory study of the Gynecologic Oncology Group

• Chemotherapy-induced neutropenia has emerged as an important biomarker in several solid tumors.
• Chemotherapy-induced neutropenia may be a biomarker for survival in untreated advanced ovarian cancer.
• Absence of chemotherapy-induced neutropenia may reflect under-dosing and ultimately attenuated antineoplastic effect.

ObjectiveTo 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.MethodsA post-hoc exploratory analysis of Gynecologic Oncology Group (GOG) protocol 182 was performed. Landmark analysis was conducted on all patients with progression-free survival > 18 weeks from the time of study entry. Neutropenia was defined as the absolute neutrophil count < 1000 mm3. 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.ResultsNeutropenic 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.ConclusionThese 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.