Abstract
BackgroundLicensed systemic treatment options for platinum-sensitive recurrent ovarian cancer are platinum-based chemotherapy and maintenance treatment with bevacizumab and poly (ADP-ribose) polymerase inhibitors. For platinum-resistant disease, several non-platinum options are available. We aimed to assess the clinical benefit of these treatments according to the European Society of Medical Oncology (ESMO)-Magnitude of Clinical Benefit Scale (MCBS).Materials and methodsA PubMed search was carried out including all studies evaluating systemic treatment of recurrent epithelial ovarian cancer, from 1990 onwards. Randomised trials with an adequate comparator and design showing a statistically significant benefit of the study arm were independently scored by two blinded observers using the ESMO-MCBS.ResultsA total of 1127 papers were identified, out of which 61 reported results of randomised trials of sufficient quality. Nineteen trials showed statistically significant results and the studied treatments were graded according to ESMO-MCBS. Only three treatments showed substantial benefit (score of 4 on a scale of 1-5) according to the ESMO-MCBS: platinum-based chemotherapy with paclitaxel in the platinum-sensitive setting and the addition of bevacizumab to chemotherapy in the platinum-resistant setting. The WEE1 inhibitor adavosertib (not licensed) also scores a 4, based on a recent small phase II study. Assessment of quality-of-life data and toxicity using the ESMO-MCBS showed to be complex, which should be taken into account in using this score for clinical decision making.ConclusionOnly a few licensed systemic therapies for recurrent ovarian cancer show substantial clinical benefit based on ESMO-MCBS scores. Trials demonstrating overall survival benefit are sparse.
Highlights
First-line therapy for advanced epithelial ovarian cancer (EOC) consists of debulking surgery and platinum-based chemotherapy
The WEE1 inhibitor adavosertib combined with gemcitabine has a preliminary score of 4 based on an overall survival (OS) benefit observed in a phase II study; this drug has not yet been licensed
Despite the use of debulking surgery for selected patients with recurrent disease, given the low chance of cure for these patients, we considered chemotherapy after debulking surgery for recurrent ovarian cancer a palliative treatment and used European Society of Medical Oncology (ESMO)-Magnitude of Clinical Benefit Scale (MCBS) forms 2 or 3
Summary
First-line therapy for advanced epithelial ovarian cancer (EOC) consists of debulking surgery and platinum-based chemotherapy. Treatment options mentioned in guidelines for this setting have limited response rates (RRs) in patients with a short PFI and most patients die of their disease within 1 year.[2] Therapies licensed for treatment of recurrent ovarian cancer, besides carboplatin and paclitaxel, are gemcitabine and bevacizumab (in combination with platinum), liposomal doxorubicin with or without trabectedin, treosulfan, melphalan, topotecan, etoposide and the poly (ADP-ribose) polymerase (PARP) inhibitors olaparib, niraparib and rucaparib. Guidelines mention these drugs as treatment options and advise that the treatment regimen should be chosen based on platinum sensitivity, previously received treatments, BRCA mutation status and physician and patients’.
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