TRUST: Trial of Radical Upfront Surgical Therapy in advanced ovarian cancer (ENGOT ov33/AGO‐OVAR OP7)

2019 ◽  
Vol 29 (8) ◽  
pp. 1327-1331 ◽  
Author(s):  
Alexander Reuss ◽  
Andreas du Bois ◽  
Philipp Harter ◽  
Christina Fotopoulou ◽  
Jalid Sehouli ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
Cytoreductive Surgery ◽  
Advanced Ovarian Cancer ◽  
Figo Stage ◽  
Complete Resection ◽  
Peritoneal Carcinoma ◽  
Exclusion Criteria ◽  
Platinum Based Chemotherapy

BackgroundPrimary cytoreductive surgery followed by chemotherapy has been considered standard management for patients with advanced ovarian cancer over decades. An alternative approach of interval debulking surgery following neoadjuvant chemotherapy was subsequently reported by two randomized phase III trials (EORTC‐GCG, CHORUS), which were criticized owing to important limitations, especially regarding the rate of complete resection.Primary ObjectiveTo clarify the optimal timing of surgical therapy in advanced ovarian cancer.Study HypothesisPrimary cytoreductive surgery is superior to interval cytoreductive surgery following neoadjuvant chemotherapy for overall survival in patients with advanced ovarian cancer.Trial DesignTRUST is an international open, randomized, controlled multi-center trial investigating overall survival after primary cytoreductive surgery versus neoadjuvant chemotherapy and subsequent interval cytoreductive surgery in patients with FIGO stage IIIB–IVB ovarian, tubal, and peritoneal carcinoma. To guarantee adequate surgical quality, participating centers need to fulfill specific quality assurance criteria (eg, ≥50% complete resection rate in upfront surgery for FIGO IIIB–IVB patients, ≥36 debulking-surgeries/year) and agree to independent audits by TRUST quality committee delegates. Patients in the primary cytoreductive surgery arm undergo surgery followed by 6 cycles of platinum-based chemotherapy, whereas patients in the interval cytoreductive surgery arm undergo 3 cycles of neoadjuvant chemotherapy after histologic confirmation of the disease, followed by interval cytoreductive surgery and subsequently, 3 cycles of platinum-based chemotherapy. The intention of surgery for both groups is complete tumor resection according to guideline recommendations.Major Inclusion/Exclusion CriteriaMajor inclusion criteria are suspected or histologically confirmed, newly diagnosed invasive epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinoma FIGO stage IIIB–IVB (IV only if resectable metastasis). Major exclusion criteria are non-epithelial ovarian malignancies and borderline tumors; prior chemotherapy for ovarian cancer; or abdominal/pelvic radiotherapy.Primary EndpointOverall survival.Sample Size772 patients.Estimated Dates for Completing Accrual and Presenting ResultsAccrual completion approximately mid-2019, results are expected after 5 years' follow-up in 2024.Trial RegistrationNCT02828618.

scholarly journals The FIGO Stage IVA Versus IVB of Ovarian Cancer: Prognostic Value and Predictive Value for Neoadjuvant Chemotherapy

2018 ◽  
Vol 28 (3) ◽  
pp. 453-458 ◽  
Author(s):  
Parvin Tajik ◽  
Roelien van de Vrie ◽  
Mohammad H. Zafarmand ◽  
Corneel Coens ◽  
Marrije R. Buist ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
Epithelial Ovarian Cancer ◽  
Prognostic Value ◽  
Median Overall Survival ◽  
Stage Iv ◽  
Figo Stage ◽  
Figo Staging ◽  
Stage Ivb

ObjectiveThe revised version of the International Federation of Gynaecology and Obstetrics (FIGO) staging system (2014) for epithelial ovarian cancer includes a number of changes. One of these is the division of stage IV into 2 subgroups. Data on the prognostic and predictive significance of this classification are scarce. The effect of neoadjuvant chemotherapy (NACT) versus primary debulking surgery (PDS) in relation to the subclassification of FIGO stage IV is also unknown.MethodsWe used data of the EORTC 55971 trial, in which 670 patients with previous stage IIIC or IV epithelial ovarian cancer were randomly assigned to PDS or NACT; 160 patients had previous stage IV. Information on previous FIGO staging and presence of pleural effusion with positive cytology were used to classify tumors as either stage IVA or IVB. We tested the association between stage IVA/IVB and survival to evaluate the prognostic value and interactions between stage, treatment, and survival to evaluate the predictive performance.ResultsAmong the 160 participants with previous stage IV disease, 103 (64%) were categorized as stage IVA and 57 (36%) as stage IVB tumors. Median overall survival was 24 months in FIGO stage IVA and 31 months in stage IVB patients (P = 0.044). Stage IVB patients treated with NACT had 9 months longer median overall survival compared with IVB patients undergoing PDS (P = 0.025), whereas in IVA patients, no significant difference was observed (24 vs 26 months, P = 0.48).ConclusionsThe reclassification of FIGO stage IV into stage IVA or IVB was not prognostic as expected. Compared with stage IVA patients, stage IVB patients have a better overall survival and may benefit more from NACT.

Upfront cytoreductive surgery versus neoadjuvant chemotherapy in advanced epithelial ovarian cancer in Indian patients

2021 ◽  
Author(s):  
Mukur Dipi Ray ◽  
Suryanarayana S.V. Deo ◽  
Lalit Kumar ◽  
Manish Kumar Gaur
Keyword(s):  
Ovarian Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Ovarian Carcinoma ◽  
Cytoreductive Surgery ◽  
Advanced Ovarian Cancer ◽  
Advanced Stages ◽  
Selection For ◽  
Selection Of Patients ◽  
Selection Of

In cases of ovarian carcinoma, primary cytoreductive surgery (CRS) is the standard treatment up to stage IIIB, but patient selection for neoadjuvant chemotherapy (NACT) in selected cases is controversial. A total of 200 patients with advanced ovarian cancer were analyzed retrospectively, according to specific selection criteria. Primary CRS was performed in 95 patients (47.5%) and interval CRS after 3–6 cycles of NACT was performed in 105 patients (52.5%). After median follow-up of 35 months, 5-year overall survival was 53.7% in the upfront CRS group and 42.2% in the NACT group. Primary CRS is the standard in advanced stages of ovarian carcinoma, but in certain subset of patients, NACT is preferred. Identifying that group is challenging but feasible. Proper selection of patients is key to successful outcomes.

Chemotherapy or upfront surgery for newly diagnosed advanced ovarian cancer: Results from the MRC CHORUS trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5500-5500 ◽  
Author(s):  
Sean Kehoe ◽  
Jane Hook ◽  
Matthew Nankivell ◽  
Gordon C. Jayson ◽  
Henry Charles Kitchener ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Controlled Trial ◽  
Advanced Ovarian Cancer ◽  
Pelvic Mass ◽  
Stage Iv ◽  
Figo Stage ◽  
Phase Iii ◽  
Initial Surgery ◽  
Platinum Based Chemotherapy ◽  
Optimal Debulking

5500 Background: First line treatment of advanced ovarian cancer (OC) is accepted to be primary surgery (PS) followed by adjuvant platinum-based chemotherapy (P-CT). However, the EORTC55971 trial suggested neoadjuvant chemotherapy (NACT) is an alternative, showing increased optimal debulking rates and reduced surgical complications without detriment to survival. CHORUS (CRUK 07/009) is the 2nd phase III randomized controlled trial to investigate timing of initial surgery in OC. Methods: Patients (pts) with clinical FIGO stage III-IV OC (pelvic mass, extrapelvic metastases and CA125/CEA ratio >25) were randomized to standard treatment (PS followed by 6 cycles P-CT) or NACT (3 cycles P-CT either side of surgery). CHORUS was designed to demonstrate non-inferiority of NACT, excluding a 6% absolute detriment in 3yr survival from 50% expected with PS (1-sided alpha 10%). Primary outcome was overall survival (OS) and secondary outcomes were progression free survival (PFS), toxicity and quality of life. Results: 550 women (276 PS, 274 NACT) were randomized from 74 centres (72 UK, 2 NZ) between Mar 2004 and Aug 2010. Baseline characteristics were well balanced: median age 65yrs, median tumor size 80mm, 25% FIGO stage IV, 19% WHO PS 2. Median follow-up was 3yrs, 410 pts have died. Treatment data are summarized in the Table. 3yr survival in the control arm was 32%. Intention to treat analysis showed a median OS of 22.8 months for PS vs 24.5 months for NACT (hazard ratio (HR) 0.87 in favor of NACT, 80% CI 0.76 – 0.98) and median PFS of 10.2 vs 11.7 months (HR 0.91, 0.81 – 1.02). OS results represent a 5% absolute benefit in 3yr survival for NACT to 37% and the upper 80% CI allows us to exclude a survival benefit for PS. Conclusions: NACT was associated with increased optimal debulking, less early mortality and similar survival in this poor prognosis group. CHORUS results are consistent with EORTC55971 and strengthen evidence that NACT is a viable alternative to PS. Clinical trial information: ISRCTN74802813. [Table: see text]

Neoadjuvant chemotherapy with six cycles of carboplatin and paclitaxel in advanced ovarian cancer patients not candidates for optimal primary surgery: Safety and effectivenes.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5540-5540
Author(s):  
Vanessa Costa Miranda ◽  
Angelo Bezerra de Sousa Fede ◽  
Carlos Henrique Dos Anjos ◽  
Juliana Ribeiro da Silva ◽  
Fernando Barbosa Sanchez ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
Disease Progression ◽  
Advanced Ovarian Cancer ◽  
Length Of Hospital Stay ◽  
Complete Response ◽  
Debulking Surgery ◽  
Stage Iiic ◽  
Primary Debulking Surgery

5540 Background: Primary debulking surgery (PDS) has been considered the standard of treatment in advanced ovarian cancer, while neoadjuvant chemotherapy, three cycles followed by interval debulking (ID) surgery, is a valid treatment alternative for patients with non-resectable disease. This study aimed to show the efficacy and safety of six cycles of neoadjuvant chemotherapy (N-CT) followed by cytoreduction, a single institution experience. Methods: Aretrospective analysis was performed of all patients (pts) with advanced ovarian cancer treated with platinum based N-CT, between January/2004 and February/2012. Results: 97 pts underwent N-CT in our institution; 78.1% and 18.8% the patients had extensive stage IIIC or IV disease at diagnosis, respectively. Median age 60 years (36 – 82). Histologic types: serous 84.5%, adenocarcinoma not specified 11.3%, endometrioide 1.0%. A median of six cycles of chemotherapy were performed. Patients did not received chemotherapy after debulking surgery. During the treatment 31.4% had grade 3/4 toxicity, the most commonly observed toxicities were hematologic toxicities and nausea, four (4.1%) patients died during chemotherapy due to disease progression. After N-CT 24.7% achieved clinical complete response, 57.7% partial response and 12.4% disease progression. From this cohort 63.1% underwent a complete resection of all macroscopic and microscopic disease (R0). Median length of hospital stay and postoperative ICU stay was 5 and 0.8 days respectively, surgical complications were not common however five (7.1%) patients needed second surgery due to operatory complications and 19 pts (27.1%) needed blood transfusion after debulking. With a median follow up of 21.8 months (0.5-139.7), median overall survival and chemotherapy-free interval were 57,7 and 9,5 months, respectively. Conclusions: Six cycles of neoadjuvant carboplatin and paclitaxel is safe, effective and does not increase perioperative and postoperative complications for patients with stage IIIC-IV not candidates for optimal/R0 PDS. The overall survival of this cohort is higher than those treated with interval debulking surgery.

scholarly journals Significance of Platinum Distribution to Predicts Platinum Resistance in Ovarian Cancer After Platinum Treatment in Neoadjuvant Chemotherapy

2021 ◽  
Author(s):  
Kaname Uno ◽  
Nobuhisa Yoshikawa ◽  
Akira Tazaki ◽  
Shoko Ohnuma ◽  
Kazuhisa Kitami ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Adjuvant Chemotherapy ◽  
Neoadjuvant Chemotherapy ◽  
Inductively Coupled Plasma ◽  
Advanced Ovarian Cancer ◽  
Type A ◽  
Platinum Resistance ◽  
Tumor Type ◽  
Platinum Based Chemotherapy ◽  
Platinum Accumulation

Abstract Most advanced ovarian cancer patients experience recurrence and develop resistance to platinum-based agents. However, the diagnosis of platinum resistance based on platinum-free interval is not always accurate and timely. In this study, we employed laser ablation inductively coupled plasma mass spectrometry to visualize platinum distribution in the tissues at the time of interval debulking surgery following neoadjuvant chemotherapy. Twenty seven patients with advanced high grade serous ovarian cancer were enrolled. Two distinct patterns of platinum distribution were observed. Type A (n = 16): platinum accumulation at the adjacent stroma but little in the tumor; type B (n = 11): even distribution of platinum through tumor and adjacent stroma. Type A was significantly correlated with worse prognosis (P = 0.031). Patients classified in type A and treated with platinum-based adjuvant chemotherapy after operation were significantly shorter period of recurrence after last platinum-based chemotherapy (P = 0.020) and diagnosed with “platinum-resistant recurrence”. Treatment with non-platinum-based chemotherapy after operation could be effective for the patients who were classified in type A. Our data indicate that the platinum resistance can be predicted prior to recurrence with platinum distribution. Thus, we will be able to select more appropriate adjuvant chemotherapy, which may possibly lead to improve patient’s prognosis.

A retrospective analysis of neoadjuvant platinum-based chemotherapy versus up-front surgery in advanced ovarian cancer

2006 ◽  
Vol 16 (Suppl 1) ◽  
pp. 47-53 ◽  
Author(s):  
H. Steed ◽  
A. M. Oza ◽  
J. Murphy ◽  
S. Laframboise ◽  
G. Lockwood ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Retrospective Analysis ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Postoperative Chemotherapy ◽  
Pleural Effusions ◽  
Primary Surgery ◽  
Platinum Based Chemotherapy ◽  
Significant Difference

The objective of this study is to compare progression-free survival (PFS) and overall survival (OS) of ovarian cancer patients treated with neoadjuvant chemotherapy and surgery to primary surgery and postoperative chemotherapy. Retrospective analysis from 1998 to 2003 of 116 patients with ovarian cancer was performed. Fifty women diagnosed by positive cytology received three cycles of carboplatin and paclitaxel. Thirty-six patients subsequently underwent cytoreductive surgery and completed three further cycles postoperatively. The OS and PFS were compared in 66 women treated with primary surgery and postoperative chemotherapy. A statistically significant difference was observed for OS (P= 0.03, HR = 1.85, CI = 1.06–3.23) and PFS (P= 0.04, HR = 1.61, CI = 1.03–2.53) favoring the primary surgery group. Due to the small numbers, age, grade, stage, pleural effusions, and histologic cell type were controlled for separately in the bivariate analyses. Controlling for stage made the results weaker. A matched subgroup survival analysis was performed on patients who had surgery following neoadjuvant chemotherapy. After matching for stage and grade and controlling age and pleural effusions (N= 28 matched pairs), there was no statistical difference for OS (P= 0.95, HR = 1.04, CI = 0.33–3.30) or PFS (P= 0.79, HR = 1.11, CI = 0.98–1.04). It is concluded that primary surgery should be considered in all patients. Neoadjuvant chemotherapy may be an alternative in a subset of women with the intent to also perform interval debulking.

scholarly journals Primary cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy (HIPEC) for FIGO stage III epithelial ovarian cancer: OVHIPEC-2, a phase III randomized clinical trial

2020 ◽  
Vol 30 (6) ◽  
pp. 888-892 ◽  
Author(s):  
Simone Koole ◽  
Ruby van Stein ◽  
Karolina Sikorska ◽  
Desmond Barton ◽  
Lewis Perrin ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Epithelial Ovarian Cancer ◽  
Cytoreductive Surgery ◽  
Hyperthermic Intraperitoneal Chemotherapy ◽  
Residual Disease ◽  
Figo Stage ◽  
Primary Objective ◽  
Phase Iii ◽  
Stage Iii

BackgroundThe addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery improves recurrence-free and overall survival in patients with FIGO stage III ovarian cancer who are ineligible for primary cytoreductive surgery. The effect of HIPEC remains undetermined in patients who are candidates for primary cytoreductive surgery.Primary objectiveThe primary objective is to evaluate the effect of HIPEC on overall survival in patients with FIGO stage III epithelial ovarian cancer who are treated with primary cytoreductive surgery resulting in no residual disease, or residual disease up to 2.5 mm in maximum dimension.Study hypothesisWe hypothesize that the addition of HIPEC to primary cytoreductive surgery improves overall survival in patients with primary FIGO stage III epithelial ovarian cancer.Trial designThis international, randomized, open-label, phase III trial will enroll 538 patients with newly diagnosed FIGO stage III epithelial ovarian cancer. Following complete or near-complete (residual disease ≤2.5 mm) primary cytoreduction, patients are randomly allocated (1:1) to receive HIPEC or no HIPEC. All patients will receive six courses of platinum-paclitaxel chemotherapy, and maintenance PARP-inhibitor or bevacizumab according to current guidelines.Major eligibility criteriaPatients with FIGO stage III primary epithelial ovarian, fallopian tube, or primary peritoneal cancer are eligible after complete or near-complete primary cytoreductive surgery. Patients with resectable umbilical, spleen, or local bowel lesions may be included. Enlarged extra-abdominal lymph nodes should be negative on FDG-PET or fine-needle aspiration/biopsy.Primary endpointThe primary endpoint is overall survival.Sample sizeTo detect a HR of 0.67 in favor of HIPEC, 200 overall survival events are required. With an expected accrual period of 60 months and 12 months additional follow-up, 538 patients need to be randomized.Estimated dates for completing accrual and presenting resultsThe OVHIPEC-2 trial started in January 2020 and primary analyses are anticipated in 2026.Trial registrationClinicalTrials.gov:NCT03772028

Primary Surgery or Neoadjuvant Chemotherapy in Advanced Ovarian Cancer: The Debate Continues…

2016 ◽  
pp. 153-162 ◽  
Author(s):  
Renee Cowan ◽  
Dennis Chi ◽  
Sean Kehoe ◽  
Matthew Nankivell ◽  
Alexandra Leary
Keyword(s):  
Ovarian Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Residual Disease ◽  
Tumor Biology ◽  
Advanced Ovarian Cancer ◽  
Debulking Surgery ◽  
Primary Debulking Surgery ◽  
Platinum Based Chemotherapy ◽  
Patient Reported ◽  
The Impact

Primary debulking surgery (PDS) followed by platinum-based chemotherapy has been the cornerstone of treatment for advanced ovarian cancer for decades. Primary debulking surgery has been repeatedly identified as one of the key factors in improving survival in patients with advanced ovarian cancer, especially when minimal or no residual disease is left behind. Achieving these results sometimes requires extensive abdominal and pelvic surgical procedures and consultation with other surgical teams. Some clinicians who propose a primary chemotherapy approach reported an increased likelihood of leaving no macroscopic disease after surgery and improved patient-reported outcomes and quality-of-life (QOL) measures. Given the ongoing debate regarding the relative benefit of PDS versus neoadjuvant chemotherapy (NACT), tumor biology may aid in patient selection for each approach. Neoadjuvant chemotherapy offers the opportunity for in vivo chemosensitivity testing. Studies are needed to determine the best way to evaluate the impact of NACT in each individual patient with advanced ovarian cancer. Indeed, the biggest utility of NACT may be in research, where this approach provides the opportunity for the investigation of predictive markers, mechanisms of resistance, and a forum to test novel therapies.

Six versus nine cycles of paclitaxel-carboplatin as first-line chemotherapy in patients with newly diagnosed epithelial advanced ovarian cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16535-e16535
Author(s):  
B. Nayl ◽  
X. Durando ◽  
C. Pomel ◽  
P. Dubray ◽  
M. Mouret-Reynier ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cytoreductive Surgery ◽  
Median Overall Survival ◽  
Progressive Disease ◽  
Advanced Ovarian Cancer ◽  
Stage Iiic ◽  
Chemotherapeutic Regimen ◽  
Platinum Based Chemotherapy ◽  
Multimodality Approach ◽  
Infusion Period

e16535 Background: A multimodality approach with cytoreductive surgery and six courses of paclitaxel-platinum-based chemotherapy is actually the mainstay of treatment of Advanced Ovarian Cancer (AOC). This study was performed to determine retrospectively the efficacy of three additional cycles of paclitaxel-carboplatin (PC) in patients with AOC who had previously demonstrated chemosensitivity to six courses of this regimen. Methods: From January 2000 to August 2008, 125 epithelial AOC (FIGO stages IIIC and IV) were diagnosed in a single institution. After a cytoreductive surgery, 51 patients received six cycles of PC (PC 6 group), 57 received 9 (PC 9 group), and 17 experienced progressive disease during treatment. The chemotherapeutic regimen consisted of intravenous paclitaxel 175 mg/m2 for a 3-hour infusion period and intravenous carboplatin AUC 5 every 3 weeks. Results: Median age was 62 years in PC6 group and 59.7 years in PC9. According to the FIGO criteria, 72.6% patients were in stage IIIC in group PC6 and 75.4% in group PC9. Except the patients who experienced refractory disease, complete clinical response at the end of chemotherapy was assessed in 71.4% patients in group PC6 and 71.9% in PC9 (p = 0.13). The median time to progression (TTP) was 26.2 months in PC6 and 29 months in PC9 (p = 0.5). The median overall survival (OS) was 106 months and 97 months respectively (p = 0.16). Conclusions: This retrospective study suggests that three cycles of consolidation chemotherapy with paclitaxel and carboplatin might not prolong duration of TTP or OS in AOC patients. No significant financial relationships to disclose.

Primary cytoreductive surgery with or without Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for FIGO stage III epithelial ovarian cancer: The OVHIPEC-2 trial in progress.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS6100-TPS6100
Author(s):  
Ruby M. van Stein ◽  
Simone N. Koole ◽  
Karolina Sikorska ◽  
Desmond P. Barton ◽  
Lewis Perrin ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Intraperitoneal Chemotherapy ◽  
Cytoreductive Surgery ◽  
Hyperthermic Intraperitoneal Chemotherapy ◽  
Figo Stage ◽  
Phase Iii ◽  
Stage Iii ◽  
Peritoneal Cancer ◽  
Anticancer Treatment

TPS6100 Background: The addition of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) to interval cytoreductive surgery improves recurrence-free and overall survival in patients with FIGO stage III ovarian cancer who are ineligible for primary cytoreductive surgery due to extensive intraperitoneal disease. The effect of HIPEC remains undetermined in patients who are eligible for primary cytoreductive surgery. We hypothesize that the addition of HIPEC to a complete or near-complete (residual disease ≤2.5 mm) primary cytoreductive surgery improves overall survival in patients with FIGO stage III ovarian cancer. Methods: This international, randomized, open-label, phase III trial enrolls patients with newly diagnosed, histological proven FIGO stage III epithelial ovarian, fallopian tube, or primary peritoneal cancer. Patients with resectable umbilical, spleen or local bowel lesions may be included. Following complete or near-complete primary cytoreduction, patients are intra-operatively randomized (1:1) to receive HIPEC or no HIPEC. Patients in both study arms will receive six courses of adjuvant carboplatin-paclitaxel and maintenance PARP-inhibitor or bevacizumab according to current guidelines. The primary endpoint is overall survival. To detect a Hazard Ratio of 0.67 in favor of HIPEC, 200 overall survival events are required. Assuming that accrual will be completed in 60 months, and 12 months additional follow-up, 538 patients need to be randomized. All randomized patients will be included in the analysis for overall survival according to the intention to treat principle. Pre-specified subgroup analyses will be performed based on stratification factors (peritoneal cancer index at start of surgery, completeness of surgery), histologic subtype (high-grade serous versus other), and BRCA mutation (BRCA1/2 mutation versus wildtype). Secondary endpoints are recurrence-free survival, time to first subsequent anticancer treatment, and treatment related complications and toxicity. Exploratory endpoints are time to second subsequent anticancer treatment, health-related quality of life, and cost-effectiveness. The Institutional Review Board of the Netherlands Cancer Institute approved the trial, which is actively enrolling patients since January 2020. Clinical trial information: NCT03772028.

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