Randomized Trial of Cytoreductive Surgery for Relapsed Ovarian Cancer

Harter, Philipp; Sehouli, Jalid; Vergote, Ignace; Ferron, Gwénaël; Reuß, Alexander; Meier, W.; Greggi, Stefano; Mosgaard, Berit Jul; Selle, Frédèric; Guyon, Frédéric; Pomel, Christophe; Lécuru, Fabrice; Zang, Rongyu; Åvall‐Lundqvist, Elisabeth; Kim, Jae Weon; Ponce, Jordi; Raspagliesi, Francesco; Kristensen, Gunnar; Classe, Jean‐Marc; Hillemanns, Peter; Jensen, Pernille Tine; Hasenburg, Annette; Ghaem‐Maghami, Sadaf; Mirza, Mansoor Raza; Lund, Bente; Reinthaller, Alexander; Santaballa, Ana; Olaitan, Adeola; Hilpert, Felix; Bois, Andreas du

doi:10.1056/nejmoa2103294

Cited by 179 publications

(140 citation statements)

References 30 publications

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“…DESKTOP III was the first RCT to show a survival benefit from such an intervention in recurrent EOC. Of note, most enrolled patients had HGSC; only six patients with LGSC were involved in the analysis [ 87 ].…”

Section: Managementmentioning

confidence: 99%

Low-Grade Serous Carcinoma of the Ovary: The Current Status

et al. 2022

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Low-grade serous carcinoma (LGSC) of the ovary is a rare histological subtype of epithelial ovarian carcinoma. It has distinct clinical behavior and a specific molecular profile. Compared with high-grade serous carcinoma, this tumor presents at a younger age, has an indolent course, and is associated with prolonged survival. LGSC can arise de novo or originate following a serous borderline tumor (SBT). Pathological differentiation between LGSC and other ovarian carcinoma histological subtypes is fundamental. Several factors might influence the overall outcome, such as the age at diagnosis, current smoking, elevated body mass index, mutational status, hormonal receptors’ expression, and Ki-67 proliferation index. Surgery is the main treatment option in LGSC, and efforts must be maximized to achieve a microscopic residual in metastatic disease. Despite being relatively chemo-resistant, adjuvant platinum-based chemotherapy remains the standard of care in LGSC. Hormonal maintenance therapy after adjuvant chemotherapy results in improved outcomes. Treatment options for disease recurrence include secondary cytoreductive surgery, chemotherapy, hormonal therapy, targeted therapy, and clinical trials. Advancements in genomic studies and targeted therapies are expected to change the treatment landscape in LGSC.

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Section: Managementmentioning

confidence: 99%

Low-Grade Serous Carcinoma of the Ovary: The Current Status

et al. 2022

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“…The “Rustin trial” changed the follow-up standard after the end of the first-line chemotherapy by eliminating the regular measurements of CA125, as early detection of relapse followed by early onset of systemic treatment did not improve survival [ 27 ]. However, most recently, the AGO-DESKTOP III showed that surgery for the first recurrence of EOC leads to improved overall survival [ 28 ]. It has not been investigated so far whether earlier detection of recurrence might lead to higher rates of complete macroscopic resection at secondary cytoreductive surgery.…”

Section: Discussionmentioning

confidence: 99%

Cell-Free-DNA-Based Copy Number Index Score in Epithelial Ovarian Cancer—Impact for Diagnosis and Treatment Monitoring

Braicu

Bois

Sehouli

et al. 2021

Cancers

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Background: Chromosomal instability, a hallmark of cancer, results in changes in the copy number state. These deviant copy number states can be detected in the cell-free DNA (cfDNA) and provide a quantitative measure of the ctDNA levels by converting cfDNA next-generation sequencing results into a genome-wide copy number instability score (CNI-Score). Our aim was to determine the role of the CNI-Score in detecting epithelial ovarian cancer (EOC) and its role as a marker to monitor the response to treatment. Methods: Blood samples were prospectively collected from 109 patients with high-grade EOC. cfDNA was extracted and analyzed using a clinical-grade assay designed to calculate a genome-wide CNI-Score from low-coverage sequencing data. Stored data from 241 apparently healthy controls were used as a reference set. Results: Comparison of the CNI-Scores of primary EOC patients versus controls yielded sensitivities of 91% at a specificity of 95% to detect OC, respectively. Significantly elevated CNI-Scores were detected in primary (median: 87, IQR: 351) and recurrent (median: 346, IQR: 1891) blood samples. Substantially reduced CNI-Scores were detected after primary debulking surgery. Using a cut-off of 24, a diagnostic sensitivity of 87% for primary and recurrent EOC was determined at a specificity of 95%. CNI-Scores above this threshold were detected in 21/23 primary tumor (91%), 36/42 of platinum-eligible recurrent (85.7%), and 19/22 of non-platinum-eligible recurrent (86.3%) samples, respectively. Conclusion: ctDNA-quantification based on genomic instability determined by the CNI-Score was a biomarker with high diagnostic accuracy in high-grade EOC. The applied assay might be a promising tool for diagnostics and therapy monitoring, as it requires no a priori information about the tumor.

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“…Despite the introduction of new medical therapies for the ovarian cancer therapeutic algorithm, cytoreductive surgery still plays a central role both in the upfront and recurrent settings. Final analysis of the DESKTOP III trial demonstrated a clear benefit for patients who met the study inclusion criteria and underwent secondary cytoreductive surgery, with a significantly longer median overall survival (HR 0.76, 95% CI 0.59 to 0.97, p=0.03), median progression-free survival (HR 0.66, 95% CI 0.54 to 0.82, p<0.001), and median time to start of first subsequent therapy (HR 0.65, 95% CI 0.52 to 0.81, p<0.001) in favor of the surgery arm compared with similar patients who did not undergo secondary surgery 12…”

Section: Introductionmentioning

confidence: 98%

Olaparib beyond progression compared with platinum chemotherapy after secondary cytoreductive surgery in patients with recurrent ovarian cancer: phase III randomized, open-label MITO 35b study, a project of the MITO-MANGO groups

Schettino

Musacchio

Bartoletti

et al. 2022

Int J Gynecol Cancer

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BackgroundPoly (ADP-ribose) polymerase inhibitors have transformed the management landscape for patients with ovarian cancer, demonstrating remarkable improvements in progression-free survival and overall survival. Unfortunately, most relapses are due to an acquired mechanism of resistance to these agents. We hypothesize that secondary cytoreductive surgery, removing resistant clones, might help to overcome the development of resistance to poly (ADP-ribose) polymerase inhibitors, prolonging their therapeutic effect.Primary ObjectiveTo determine the efficacy of olaparib beyond progression compared with standard platinum-based chemotherapy in patients with recurrent ovarian cancer progressed during or after poly (ADP-ribose) polymerase inhibitor maintenance therapy after secondary cytoreductive surgery.Study HypothesisOlaparib administered beyond progression is more effective in increasing progression-free survival and progression-free survival 2 compared with second-line platinum-based chemotherapy in patients after secondary cytoreductive surgery.Trial DesignPhase III, randomized, open-label, multicenter trial. Eligible patients will be randomized in a 1:1 ratio to receive olaparib or platinum-based chemotherapy of the investigator’s choice.Major Eligibility CriteriaEligible patients must have high-grade serous or endometrioid ovarian cancer progressed during or after first-line poly (ADP-ribose) polymerase inhibitor maintenance therapy and must have undergone secondary cytoreductive surgery.Primary EndpointThe dual primary endpoints will include progression-free survival and progression-free survival 2. Progression-free survival is defined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as the time between randomization and progression or death from any cause. Progression-free survival 2 is defined by the investigator using RECIST version 1.1 as the time frame from randomization to the second progression or death from any cause after subsequent treatment.Sample SizeApproximately 200 patients will be enrolled in this study.Estimated Dates for Completing Accrual and Presenting ResultsEnrollment will be completed in 2024. Results will be presented in 2026.Trial RegistrationEudraCT 2021-000245-41 NCT05255471

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Randomized Trial of Cytoreductive Surgery for Relapsed Ovarian Cancer

Cited by 179 publications

References 30 publications

Low-Grade Serous Carcinoma of the Ovary: The Current Status

Low-Grade Serous Carcinoma of the Ovary: The Current Status

Cell-Free-DNA-Based Copy Number Index Score in Epithelial Ovarian Cancer—Impact for Diagnosis and Treatment Monitoring

Olaparib beyond progression compared with platinum chemotherapy after secondary cytoreductive surgery in patients with recurrent ovarian cancer: phase III randomized, open-label MITO 35b study, a project of the MITO-MANGO groups

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