Adherence to Chemotherapy Among Patients with Advanced Epithelial Ovarian Cancer in the Netherlands and Its Impact on Survival: A Nationwide Cohort Study

ObjectivePopulation-based information regarding adherence to first-line chemotherapy in epithelial ovarian cancer is scarce. This study aimed to evaluate chemotherapy adherence, reasons for chemotherapy modifications, and associations with overall survival. MethodsAdvanced-stage epithelial ovarian cancer patients diagnosed between January 2015 and December 2021 were identified from the Netherlands Cancer Registry. Patients who underwent cytoreductive surgery combined with platinum- and taxane-based chemotherapy were included. Patients were categorized into two groups: adherent (patients without modifications) and non-adherent (patients with modifications: dose reduction, chemotherapy interruption, and/or reduction in chemotherapy cycles). Reasons for modifications were assessed. Kaplan-Meier survival curves and Cox proportional hazards models were used to analyze overall survival. ResultsAmong the cohort (N = 3,687), 54% of patients underwent chemotherapy modifications. Dose reduction (38%) was the most common, followed by interruption (24%) and reduction in chemotherapy cycles (9%). Non-adherence was associated with poorer performance scores, higher comorbidity indices, and undergoing primary cytoreductive surgery. Neurotoxicity and hematologic toxicity were the primary reasons for modifications in platinum (33% and 37%) and taxane (47% and 35%) agents. No association with survival was found for dose reduction and interruption. However, reduction in chemotherapy cycles was associated with lower 5-year overall survival (32% (95% CI 26%-38%) vs. 36% (95% CI 34%-38%)), remaining significant after multivariable adjustment (hazard ratio 1.36; 95% CI 1.17-1.59). ConclusionA significant proportion of Dutch advanced-stage epithelial ovarian cancer patients undergo chemotherapy modifications. No impact on overall survival was found for dose reduction or chemotherapy interruption, warranting prospective studies. Reduction in chemotherapy cycles was negatively associated with overall survival, possibly reflecting underlying treatment ineffectiveness. Key messagesO_ST_ABSWhat is already known on this topicC_ST_ABSGuideline-recommended chemotherapy for advanced epithelial ovarian cancer is often difficult to deliver in routine practice, and real-world data on adherence and its impact on survival are limited. What this study addsIn this nationwide retrospective cohort, over half of patients experienced chemotherapy modifications; dose reductions and interruptions were not associated with poorer overall survival, whereas a reduction in the number of cycles showed an association with worse outcomes, although this may partly reflect underlying disease severity or treatment response. How this study might affect research, practice or policyOur findings suggest that standard dosing and treatment duration of six cycles may not always be necessary, emphasizing the need to tailor treatment plans to optimize both efficacy and tolerability in advanced-stage epithelial ovarian cancer patients