Who really benefits from intraperitoneal chemotherapy for advanced ovarian cancer? A treatment‐free survival analysis of the AICE trial

Abstract Objective To investigate whether peritoneal disease extent can predict the survival benefit of intraperitoneal/intravenous (IP/IV) chemotherapy in ovarian cancer. Design A treatment‐free survival (TFS) analysis. Setting Five‐centre trial. Population An extended follow‐up of the Additional Intraperitoneal Cisplatin and Etoposide in ovarian cancer (AICE) trial (NCT01669226), with data cut‐off on 27 August 2020. Patients were categorised into subgroups with high tumour burden (HTB) and low tumour burden (LTB). Methods Overall survival (OS) was divided into time on protocol treatment exposure (T), time free of subsequent treatment or death (TFS) and time after the first subsequent therapy (REL). TFS analyses and quality‐adjusted OS were calculated by multiplying the mean time in each health state by its assigned utility: quality‐adjusted OS = u t × T + TFS + u rel × REL. Main outcome measures The area under each Kaplan–Meier curve was estimated using the 96‐month restricted mean time, with threshold utility analyses used to illustrate quality‐adjusted OS comparisons. Results In the HTB subgroup, the restricted mean TFS was 33.9 months and 18.7 months in the IP/IV and IV groups, respectively ( p = 0.005), with a significant quality‐adjusted OS gain (13.2–16.0 months). In the LTB subgroup, IP/IV therapy yielded no survival benefit in either TFS ( p = 0.268) or quality‐adjusted OS (range: 1.4–6.3 months). Conclusions Both TFS and quality‐adjusted OS was longer across all utility weight values with IP/IV than with standard IV therapy in the HTB subgroup, whereas patients in the LTB subgroup did not benefit from the therapy. The tumour burden of ovarian cancer should be assessed before deciding on IP/IV versus IV treatment.