Among women with advanced ovarian cancer with a
BRCA
mutation who had a response after platinum-based therapy, the median progression-free survival was approximately 3 years longer with the use of ...olaparib maintenance therapy for 2 years than with placebo.
Abstract Objective To develop an updated laparoscopy-based model to predict incomplete cytoreduction (RT > 0) in advanced epithelial ovarian cancer (AEOC), after the introduction of upper abdominal ...surgery (UAS). Patients and methods The presence of omental cake, peritoneal extensive carcinomatosis, diaphragmatic confluent carcinomatosis, bowel infiltration, stomach and/or spleen and/or lesser omentum infiltration, and superficial liver metastases was evaluated by staging laparoscopy (S-LPS) in a consecutive series of 234 women with newly diagnosed AEOC, receiving laparotomic PDS after S-LPS. Parameters showing a specificity ≥ 75%, PPV ≥ 50%, and NPV ≥ 50% received 1 point score, with an additional one point in the presence of an accuracy of ≥ 60% in predicting incomplete cytoreduction. The overall discriminating performance of the LPS-PI was finally estimated by ROC curve analysis. Results No-gross residual disease at PDS was achieved in 135 cases (57.5%). Among them, UAS was required in 72 cases (53.3%) for a total of 112 procedures, and around 25% of these patients received bowel resection, excluding recto-sigmoid resection. We observed a very high overall agreement between S-LPS and laparotomic findings, which ranged from 74.7% for omental cake to 94.8% for stomach infiltration. At a LPS-PIV ≥ 10 the chance of achieving complete PDS was 0, and the risk of unnecessary laparotomy was 33.2%. Discriminating performance of LPS-PI was very high (AUC = 0.885). Conclusions S-LPS is confirmed as an accurate tool in the prediction of complete PDS in women with AEOC. The updated LPS-PI showed improved discriminating performance, with a lower rate of inappropriate laparotomic explorations at the established cut-off value of 10.
Mirvetuximab soravtansine (MIRV) is an antibody-drug conjugate comprising a folate receptor alpha (FRα)-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent. ...The randomized, open-label, phase III study FORWARD I compared MIRV and investigator's choice chemotherapy in patients with platinum-resistant epithelial ovarian cancer (EOC).
Eligible patients with 1-3 prior lines of therapy and whose tumors were positive for FRα expression were randomly assigned, in a 2 : 1 ratio, to receive MIRV (6 mg/kg, adjusted ideal body weight) or chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan). The primary endpoint was progression-free survival PFS, Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, blinded independent central review in the intention-to-treat (ITT) population and in the prespecified FRα high population.
A total of 366 patients were randomized; 243 received MIRV and 109 received chemotherapy. The primary endpoint, PFS, did not reach statistical significance in either the ITT hazard ratio (HR), 0.98, P = 0.897 or the FRα high population (HR, 0.69, P = 0.049). Superior outcomes for MIRV over chemotherapy were observed in all secondary endpoints in the FRα high population including improved objective response rate (24% versus 10%), CA-125 responses (53% versus 25%), and patient-reported outcomes (27% versus 13%). Fewer treatment-related grade 3 or higher adverse events (25.1% versus 44.0%), and fewer events leading to dose reduction (19.8% versus 30.3%) and treatment discontinuation (4.5% versus 8.3%) were seen with MIRV compared with chemotherapy.
In patients with platinum-resistant EOC, MIRV did not result in a significant improvement in PFS compared with chemotherapy. Secondary endpoints consistently favored MIRV, particularly in patients with high FRα expression. MIRV showed a differentiated and more manageable safety profile than chemotherapy.
•In platinum-resistant EOC MIRV did not significantly improve PFS over chemotherapy.•No unexpected toxicities were observed, and tolerability profiles were consistent with those observed in previous studies.•The most promising signals of efficacy were observed with MIRV in patients with high FRα expression.•The findings support ongoing trials designed to select the patients with EOC most likely to derive benefit from this agent.
The consensus statements regarding first-line therapies in women with ovarian cancer, reached at the Fifth Ovarian Cancer Consensus Conference held in Tokyo, Japan, in November 2015 are reported. ...Three topics were reviewed and the following statements are recommended: (i) Surgery: the subgroups that should be considered in first-line ovarian cancer clinical trials should be (a) patients undergoing primary debulking surgery and (b) patients receiving neo-adjuvant chemotherapy. The amount of residual disease following surgery should further stratify patients into those with absent gross residual disease and others. (ii) Control arms for chemotherapy: for advanced stage ovarian cancer the standard is intravenous 3-weekly carboplatin and paclitaxel. Acceptable alternatives, which should be stratified variables in trials when more than one regimen is offered, include weekly paclitaxel plus 3-weekly carboplatin, the addition of bevacizumab to 3-weekly carboplatin and paclitaxel, and intraperitoneal therapy. (iii) Trial Endpoints: overall survival is the preferred primary endpoint for first-line clinical trials with or without a maintenance component. Progression-free survival (PFS) is an alternative primary endpoint, but if PFS is chosen overall survival must be measured as a secondary endpoint and PFS must be supported by additional endpoints, including predefined patient reported outcomes and time to first or second subsequent therapy. For neoadjuvant therapy, additional ‘window of opportunity’ endpoints should be included.
To compare survival outcomes and peri-operative complications in patients with advanced ovarian cancer with 1–10 mm residual disease (RD) at primary debulking surgery (PDS) versus those achieving no ...gross residual disease (NGR) at interval debulking surgery (IDS).
Patients operated with the intent of complete cytoreduction for epithelial ovarian/fallopian tube/primary peritoneal cancer, FIGO stage IIIC-IV, RD 1–10 mm at PDS and NGR at IDS, between 01/2010 and 12/2016, were retrospectively included. All patients had at least 2-years of follow-up completed.
207 patients were included (59 PDS and 148 IDS). Patients in PDS group were younger and had a higher surgical complexity score. There was a higher rate of intra- and major early post-operative complications in the group of PDS vs IDS (16.9% vs 1.3% and 28.8% vs 2.0%, p < 0.0001 respectively). After a median follow up of 56.4 months (range 59.2–65.4), 117 (56.5%) patients died of disease in the whole population. Forty-eight (81.4%) patients had progression/recurrent disease in the PDS group and 120 (81.1%) in the IDS group. Median PFS was 16.2 months and 18.9 months for PDS and IDS group, respectively (p = 0.111). Median OS was 41.4 months and 52.4 months for PDS and IDS group, respectively (p = 0.022).
IDS should be considered the preferred treatment in case millimetric residual disease is expected at PDS in view of the superimposable PFS and the reduced number of perioperative complications.
•Surgical complexity score was higher in primary debulking when compared with interval debulking surgery.•Primary debulking was associated with higher incidence of intra- and post-operative complications than interval debulking.•No progression-free survival difference was found between the two groups of patients.•Complete cytoreduction at primary and interval cytoreduction is the major prognostic factor in advanced ovarian cancer.
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