Feasibility and outcome of interval debulking surgery (IDS) after carboplatin-paclitaxel-bevacizumab (CPB): A subgroup analysis of the MITO-16A-MaNGO OV2A phase 4 trial
Introduction
Ovarian cancer (OC) is the most lethal among gynaecologic tumours. It is estimated that in Europe, in 2015, 31.378 women will die due to OC [1]. The main reasons for the dismal prognosis of OC include the late discovery of the tumour, with most of the patients being diagnosed at an advanced stage, the high tumour burden at the diagnosis, and the development of chemotherapy resistance at recurrence, despite an initial high response to treatment. The therapeutic mainstay of the advanced disease is the primary maximum cytoreductive surgical effort followed by the carboplatin-paclitaxel chemotherapy. However, optimal primary cytoreduction has been reported to be possible only in 40% to 80% of the cases largely depending on surgeon's expertise. In the remaining cases neoadjuvant chemotherapy is offered to patients who are not eligible for frontline surgery in order to facilitate tumour debulking.
The natural history of the OC has been recently challenged by several advances in the knowledge of the disease's biology and by therapeutic targeting of crucial molecular hallmarks of OC. Among these, angiogenesis has been shown to exert a major role in promoting and sustaining gynaecologic tumours and is regarded as one of the most important therapeutic target in OC [2]. Several antiangiogenic drugs have been tested for the treatment of ovarian cancer. Among these, the monoclonal antibody bevacizumab, has been showed to significantly prolong PFS in chemonaïve patients [3], [4], and both in platinum sensitive [5] and resistant [6] recurrence in patient who did not receive bevacizumab in first line. Based on these results bevacizumab has been approved, by European Medicines Agency (EMA), for the treatment of FIGO stage IIIB-C-IV OC patients. More recently, the addition of bevacizumab to platinum-based chemotherapy failed to show a significant impact on the survival of a subset of 69 platinum-sensitive recurrent OC patients who had received bevacizumab within the first-line treatment, although in this population it elicited a higher response rate [7]. Noteworthy, in the two pivotal trials, first line bevacizumab was given after primary cytoreductive surgery [3], [4]. Data regarding bevacizumab in combination to standard chemotherapy in the neoadjuvant setting are not available.
We designed the MITO16A-MaNGO OV2A trial to evaluate potentially predictive/prognostic biomarkers useful to select patients with OC who might benefit from bevacizumab in first line. Administration of neoadjuvant chemotherapy was allowed according to inclusion criteria.
Results presented here refer to an unplanned analysis, aimed at describing the impact of bevacizumab on feasibility of interval debulking surgery and on the rate of complications, in the cohort of patients receiving bevacizumab as part of a neoadjuvant treatment in first line.
Section snippets
Study design
The MITO16A-MaNGO OV2A (www.clinicaltrials.gov number: NCT01706120) is a phase IV, non-randomized, trial evaluating the potential prognostic role of multiple molecular and clinical biomarkers in a population of advanced ovarian cancer patients receiving carboplatin-paclitaxel and bevacizumab as first line treatment. Patients were enrolled through the web (http:\\www.usc-intnapoli.net).
Data were collected through the above reported website with dedicated electronic CRF. The data presented here
Results
The overall MITO 16A-MaNGO OV2A population of 400 patients was accrued between October 2012 and March 2014. Among these, 79 (19.8%) patients received neoadjuvant chemotherapy followed by IDS within the study. Of these, only 74 patients received at least one dose of bevacizumab as part of the study treatment before IDS. Main characteristics of these patients are showed in Table 1. The median age was 61.2 (inter-quartile range, IQR: 53.1–69.8); most patients had a FIGO IIIC disease (70%), had
Discussion
The vast majority of patients affected by OC are diagnosed with advanced stage disease [8]. Complete primary surgery followed by platinum-based chemotherapy remains the mainstay of treatment of advanced OC patients, but unfortunately, in a variable percentage of them, this strategy cannot be applicable because of the tumour burden or for reasons related to poor performance status of the patient which preclude major surgery. Therefore, in order to significantly impact on survival, clinical
Conflict of interest statement
FP declared grant and non-financial support from Roche and personal fees from Roche, Amgen, Bayer, Lilly, Novartis and Daiichi-Sankyo. FR declared grant, personal fees and non-financial Support from Roche, Pharmamar and Astra Zeneca. NC declared personal fees from Roche, Pharmamar, Astra Zeneca, Amgen, Clovis, Debiopharm, Tesaro. SP declared grant and personal fees from Roche and personal fees from Astra Zeneca.
Financial disclosure
MITO-16A-MaNGO OV2A is an academic non-profit trial. Sponsor of the study is National Cancer Institute of Naples, which owns the full property of data. Roche SPA provided Bevacizumab and partial funding.
Acknowledgements
Dr. S. Pignata is a recipient of a grant from Associazione Italiana per la Ricerca sul Cancro (AIRC).
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Efficacy and safety of neoadjuvant chemotherapy containing anti-angiogenic drugs, immunotherapy, or PARP inhibitors for ovarian cancer
2024, Critical Reviews in Oncology/HematologyPostoperative adjuvant dose-dense chemotherapy with bevacizumab and maintenance bevacizumab after neoadjuvant chemotherapy for advanced ovarian cancer: A phase II AGOG/TGOG trial
2021, European Journal of Obstetrics and Gynecology and Reproductive BiologyCitation Excerpt :The following randomized phase 2 ANTHALYA study compared with or without bevacizumab added to NAC, the result showed better complete resection rate in bevacizumab arm than chemotherapy alone (58.6 % vs. 51.4 %) [18]. The MITO16A-Mango OV2A study subgroup analysis showed 63.5 % of complete cytoreduction rate with bevacizumab during NAC phase [19]. An Italian retrospective matched control study found a higher CA125 response (48 % vs 35.1 %; p = 0.041) but a similar complete resection rate (80 % vs 72.3 %) of the bevacizumab group [20].
Survival outcome and perioperative complication related to neoadjuvant chemotherapy with carboplatin and paclitaxel for advanced ovarian cancer: A systematic review and meta-analysis
2020, European Journal of Surgical OncologyCitation Excerpt :Among them, 305 articles were excluded because of being reports on ongoing trials without survival outcomes, retrospective studies, reports on non-target diseases, or non-English articles. The remaining 28 articles met the criteria for further assessment, being reports of studies that compared PDS with carboplatin/taxane-based NACT followed by IDS for advanced epithelial ovarian cancer, and full content review of these articles was performed (Supplemental Table S3) [6–8,21–40]. Finally, four RCTs were identified (EORTC 55971, CHORUS, JGOG0602, and SCORPION), which enrolled patients with FIGO stage II-IV ovarian cancer and met the inclusion criteria for this review (Fig. 2) [39,41–43].
HIPEC in ovarian cancer: What should we expect?
2019, Bulletin du CancerMedical treatment in ovarian cancers newly diagnosed: Article drafted from the French Guidelines in oncology entitled “Initial management of patients with epithelial ovarian cancer” developed by FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY under the aegis of CNGOF and endorsed by INCa
2019, Gynecologie Obstetrique Fertilite et Senologie
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