TY - JOUR
T1 - Cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy in patients with advanced ovarian cancer (OVHIPEC-1)
T2 - final survival analysis of a randomised, controlled, phase 3 trial
AU - Aronson, S. Lot
AU - Lopez-Yurda, Marta
AU - Koole, Simone N.
AU - Schagen van Leeuwen, Jules H.
AU - Schreuder, Hendrik W. R.
AU - Hermans, Ralph H. M.
AU - de Hingh, Ignace H. J. T.
AU - van Gent, Mignon D. J. M.
AU - Arts, Henriëtte J. G.
AU - van Ham, Maaike A. P. C.
AU - van Dam, Peter A.
AU - Vuylsteke, Peter
AU - Verwaal, Victor J.
AU - van de Vijver, Koen K.
AU - Aaronson, Neil K.
AU - Sonke, Gabe S.
AU - van Driel, Willemien J.
N1 - Funding Information: WJvD was the coordinating principal investigator for the study and was responsible for funding acquisition. SLA, SNK, JHSvL, HWRS, RHMH, IHJTdH, MDJMvG, HJGA, MAPCvH, PAvD, PV, GSS, and WJvD were involved in patient accrual and data collection. KKvdV performed central pathology review. AGJA and NKA had clinical advisory roles. SLA, ML-Y, GSS, and WJvD have accessed and verified the data. The formal analysis was done by SLA and ML-Y. SLA, ML-Y, GSS, WJvD interpreted the data. SLA wrote the original draft of the manuscript. GSS and WJvD supervised the study. All authors were involved in critically revising the report. All authors had access to the data in the study and approved the final version of the manuscript. All authors take responsibility for decision to submit the manuscript for publication. Funding Information: Funding for this study was provided by The Dutch Cancer Society (KWF Kankerbestrijding; NKI 2006–4176). HWRS, IHJTdH, and AGJA are members of The Dutch Peritoneal Oncology Group. GSS and WJvD are members of The Dutch Gynecological Oncology Group. In addition to the authors, the following collaborators participated in the study: S Achten, H van Berkum-Kuipers, J O A M van Baal, D Boerma, Y D Boomgaard, R J van Ginkel, K Havenga, M Zournas-Hermans, H M Horlings, A D R Huitema, A de Jong, J Kant, A M Kosterman, M Los, D W G van Loosdregt, P B Ottevanger, L M Pronk, A K L Reyners, K Sikorska, P J Tanis, A Torres Acosta, A M Westermann, M J Wiezer, and P O Witteveen. We thank all the participating patients in this trial, their families, and caretakers; the NKI-AVL Core Facility Molecular Pathology & Biobanking and the Genomic Core Facility for laboratory support and collaboration; the Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON) for the germline-status data delivery; and the nationwide network and registry of histopathology and cytopathology in the Netherlands, PALGA: Dutch Pathology Registry, for the national collection and distribution of tissue samples. Publisher Copyright: © 2023 Elsevier Ltd
PY - 2023/10/1
Y1 - 2023/10/1
N2 - Background: The OVHIPEC-1 trial previously showed that the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery resulted in improved progression-free and overall survival compared with cytoreductive surgery alone at 4·7 years of follow-up in patients with stage III epithelial ovarian cancer who were ineligible for primary cytoreduction. We report the final survival outcomes after 10 years of follow-up. Methods: In this open-label, randomised, controlled, phase 3 trial, patients with primary epithelial stage III ovarian cancer were recruited at eight HIPEC centres in the Netherlands and Belgium. Patients were eligible if they were aged 18–76 years, had not progressed during at least three cycles of neoadjuvant carboplatin plus paclitaxel, had a WHO performance status score of 0–2, normal blood counts, and adequate renal function. Patients were randomly assigned (1:1) to undergo interval cytoreductive surgery without HIPEC (surgery group) or with HIPEC (100 mg/m2 cisplatin; surgery-plus-HIPEC group). Randomisation was done centrally by minimisation with a masked web-based allocation procedure at the time of surgery when residual disease smaller than 10 mm diameter was anticipated, and was stratified by institution, previous suboptimal cytoreductive surgery, and number of abdominal regions involved. The primary endpoint was progression-free survival and a secondary endpoint was overall survival, analysed in the intention-to-treat population (ie, all randomly assigned patients). This study is registered with ClinicalTrials.gov, NCT00426257, and is closed. Findings: Between April 1, 2007, and April 30, 2016, 245 patients were enrolled and followed up for a median of 10·1 years (95% CI 8·4–12·9) in the surgery group (n=123) and 10·4 years (95% CI 9·5–13·3) in the surgery-plus-HIPEC group (n=122). Recurrence, progression, or death occurred in 114 (93%) patients in the surgery group (median progression-free survival 10·7 months [95% CI 9·6–12·0]) and 109 (89%) patients in the surgery-plus-HIPEC group (14·3 months [12·0–18·5]; hazard ratio [HR] 0·63 [95% CI 0·48–0·83], stratified log-rank p=0·0008). Death occurred in 108 (88%) patients in the surgery group (median overall survival 33·3 months [95% CI 29·0–39·1]) and 100 (82%) patients in the surgery-plus-HIPEC group (44·9 months [95% CI 38·6–55·1]; HR 0·70 [95% CI 0·53–0·92], stratified log-rank p=0·011). Interpretation: These updated survival results confirm the long-term survival benefit of HIPEC in patients with primary stage III epithelial ovarian cancer undergoing interval cytoreductive surgery. Funding: Dutch Cancer Foundation (KWF Kankerbestrijding).
AB - Background: The OVHIPEC-1 trial previously showed that the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery resulted in improved progression-free and overall survival compared with cytoreductive surgery alone at 4·7 years of follow-up in patients with stage III epithelial ovarian cancer who were ineligible for primary cytoreduction. We report the final survival outcomes after 10 years of follow-up. Methods: In this open-label, randomised, controlled, phase 3 trial, patients with primary epithelial stage III ovarian cancer were recruited at eight HIPEC centres in the Netherlands and Belgium. Patients were eligible if they were aged 18–76 years, had not progressed during at least three cycles of neoadjuvant carboplatin plus paclitaxel, had a WHO performance status score of 0–2, normal blood counts, and adequate renal function. Patients were randomly assigned (1:1) to undergo interval cytoreductive surgery without HIPEC (surgery group) or with HIPEC (100 mg/m2 cisplatin; surgery-plus-HIPEC group). Randomisation was done centrally by minimisation with a masked web-based allocation procedure at the time of surgery when residual disease smaller than 10 mm diameter was anticipated, and was stratified by institution, previous suboptimal cytoreductive surgery, and number of abdominal regions involved. The primary endpoint was progression-free survival and a secondary endpoint was overall survival, analysed in the intention-to-treat population (ie, all randomly assigned patients). This study is registered with ClinicalTrials.gov, NCT00426257, and is closed. Findings: Between April 1, 2007, and April 30, 2016, 245 patients were enrolled and followed up for a median of 10·1 years (95% CI 8·4–12·9) in the surgery group (n=123) and 10·4 years (95% CI 9·5–13·3) in the surgery-plus-HIPEC group (n=122). Recurrence, progression, or death occurred in 114 (93%) patients in the surgery group (median progression-free survival 10·7 months [95% CI 9·6–12·0]) and 109 (89%) patients in the surgery-plus-HIPEC group (14·3 months [12·0–18·5]; hazard ratio [HR] 0·63 [95% CI 0·48–0·83], stratified log-rank p=0·0008). Death occurred in 108 (88%) patients in the surgery group (median overall survival 33·3 months [95% CI 29·0–39·1]) and 100 (82%) patients in the surgery-plus-HIPEC group (44·9 months [95% CI 38·6–55·1]; HR 0·70 [95% CI 0·53–0·92], stratified log-rank p=0·011). Interpretation: These updated survival results confirm the long-term survival benefit of HIPEC in patients with primary stage III epithelial ovarian cancer undergoing interval cytoreductive surgery. Funding: Dutch Cancer Foundation (KWF Kankerbestrijding).
UR - http://www.scopus.com/inward/record.url?scp=85172660944&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/S1470-2045(23)00396-0
DO - https://doi.org/10.1016/S1470-2045(23)00396-0
M3 - Article
C2 - 37708912
SN - 1470-2045
VL - 24
SP - 1109
EP - 1118
JO - The Lancet Oncology
JF - The Lancet Oncology
IS - 10
ER -