Central radiology assessment of the randomized phase III open-label OVHIPEC-1 trial in ovarian cancer

Abstract

IntroductionHyperthermic intraperitoneal chemotherapy (HIPEC) improved investigator-assessed recurrence-free survival and overall survival in patients with stage III ovarian cancer in the phase III OVHIPEC-1 trial. We analyzed whether an open-label design affected the results of the trial by central blinded assessment of recurrence-free survival, and tested whether HIPEC specifically targets the peritoneal surface by analyzing the site of disease recurrence.MethodsOVHIPEC-1 was an open-label, multicenter, phase III trial that randomized 245 patients after three cycles of neoadjuvant chemotherapy to interval cytoreduction with or without HIPEC using cisplatin (100 mg/m2). Patients received three additional cycles of chemotherapy after surgery. Computed tomography (CT) scans and serum cancer antigen 125 (CA125) measurements were performed during chemotherapy, and during follow-up. Two expert radiologists reviewed all available CT scans. They were blinded for treatment allocation and clinical outcome. Central revision included Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 measurements and peritoneal cancer index scorings at baseline, during treatment, and during follow-up. Time to centrally-revised recurrence was compared between study arms using Cox proportional hazard models. Subdistribution models compared time to peritoneal recurrence between arms, accounting for competing risks.ResultsCT scans for central revision were available for 231 patients (94%) during neoadjuvant treatment and 212 patients (87%) during follow-up. Centrally-assessed median recurrence-free survival was 9.9 months in the surgery group and 13.2 months in the surgery+HIPEC group (HR for disease recurrence or death 0.72, 95% CI 0.55 to 0.94; p=0.015). The improved recurrence-free survival and overall survival associated with HIPEC were irrespective of response to neoadjuvant chemotherapy and baseline peritoneal cancer index. Cumulative incidence of peritoneal recurrence was lower after surgery+HIPEC, but there was no difference in extraperitoneal recurrences.ConclusionCentrally-assessed recurrence-free survival analysis confirms the benefit of adding HIPEC to interval cytoreductive surgery in patients with stage III ovarian cancer, with fewer peritoneal recurrences. These results rule out radiological bias caused by the open-label nature of the study.

Hyperthermic Intraperitoneal Chemotherapy After Interval Cytoreductive Surgery for Patients With Advanced-Stage Ovarian Cancer Who Had Received Neoadjuvant Chemotherapy

“…As described previously, HIPEC may alter the recurrence pattern in ovarian cancer and was associated with a lower rate of peritoneal recurrence, which was consistent with our findings . Ceresoli et al reported that recurrence in the peritoneum was associated with poor OS among patients who underwent ICS with HIPEC.…”

Hyperthermic intraperitoneal chemotherapy (HIPEC) for the management of primary advanced and recurrent ovarian cancer: a systematic review and meta-analysis of randomized trials

“… 27 Five studies were excluded due to not being randomized 28 , 29 and due to researching outcomes unrelated to our analysis. 30 , 31 , 32 The eligible studies were conducted in South Korea, 22 Spain, 23 USA, 24 , 27 the Netherlands, 25 Greece 26 and three of them were multicenter. 22 , 24 , 25 Overall 737 patients were randomized across six trials; among these four studies (519 patients) 22 , 23 , 25 , 27 concerned the experimental use of HIPEC in primary ovarian cancer and two (218 patients) its investigational use in recurrent settings.…”

Hyperthermic Intraperitoneal Chemotherapy for Ovarian and Colorectal Cancer

“…These latter 2 observations indicate that any potential surgical bias has had minimal prognostic impact. Furthermore, central revision of recurrence-free survival ruled out radiological bias . Regarding the alleged imbalance in specific baseline characteristics such as histologic subtype, the general principle of randomization ensured equality of prognosis based on all known and unknown prognostic factors.…”