RT Journal Article
SR Electronic
T1 Central radiology assessment of the randomized phase III open-label OVHIPEC-1 trial in ovarian cancer
JF International Journal of Gynecologic Cancer
JO Int J Gynecol Cancer
FD BMJ Publishing Group Ltd
SP ijgc-2020-001825
DO 10.1136/ijgc-2020-001825
A1 Simone N. Koole
A1 Leigh Bruijs
A1 Cristina Fabris
A1 Karolina Sikorska
A1 Maurits Engbersen
A1 Jules H. Schagen van Leeuwen
A1 Henk W.R. Schreuder
A1 Ralph H. Hermans
A1 Jacobus van der Velden
A1 Henriette J.G. Arts
A1 Maaike van Ham
A1 Peter Van Dam
A1 Peter Vuylsteke
A1 Max Lahaye
A1 Gabe Sonke
A1 Willemien van Driel
YR 2020
UL http://ijgc.bmj.com/content/early/2020/10/11/ijgc-2020-001825.abstract
AB Introduction Hyperthermic 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.Methods OVHIPEC-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.Results CT 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.Conclusion Centrally-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.