Niraparib Maintenance Therapy in Patients With Recurrent Ovarian Cancer After a Partial Response to the Last Platinum-Based Chemotherapy in the ENGOT-OV16/NOVA Trial

PURPOSEIn the ENGOT-OV16/NOVA trial (ClinicalTrials.gov identifier: NCT01847274), maintenance therapy with niraparib, a poly(ADP-ribose) polymerase inhibitor, prolonged progression-free survival in patients with platinum-sensitive, recurrent ovarian cancer who had a response to their last platinum-based chemotherapy. The objective of the study was to assess the clinical benefit and patient-reported outcomes in patients who had a partial response (PR) and complete response (CR) to their last platinum-based therapy.PATIENTS AND METHODSA total of 553 patients were enrolled in the trial. Of 203 patients with a germline BRCA mutation (gBRCAmut), 99 had a PR and 104 had a CR to their last platinum-based therapy; of 350 patients without a confirmed gBRCAmut (non?gBRCAmut), 173 had a PR and 177 had a CR. Post hoc analyses were carried out to evaluate safety and the risk of progression in these patients according to gBRCAmut status and response to their last platinum-based therapy. Ovarian cancer?specific symptoms and quality of life were assessed using the Functional Assessment of Cancer Therapy?Ovarian Symptom Index.RESULTSProgression-free survival was improved in patients treated with niraparib compared with placebo in both the gBRCAmut cohort (PR: hazard ratio [HR], 0.24; 95% CI, 0.131 to 0.441; P < .0001; CR: HR, 0.30; 95% CI, 0.160 to 0.546; P < .0001) and the non?gBRCAmut cohort (PR: HR, 0.35; 95% CI, 0.230 to 0.532; P < .0001; CR: HR, 0.58; 95% CI, 0.383 to 0.868; P = .0082). The incidence of any-grade and grade 3 or greater adverse events was manageable. No meaningful differences were observed between niraparib and placebo in PR and CR subgroups with respect to patient-reported outcomes.CONCLUSIONPatients achieved clinical benefit from maintenance treatment with niraparib regardless of response to the last platinum-based therapy

Cancer de l’ovaire : la rechute précoce

National audienceLa rechute précoce est définie par une récidive qui survient moins de 6 mois après la dernière injection de chimiothérapie à base de platine. Elle peut être primaire ou secondaire, et après une ou plusieurs lignes de traitements avec un sel de platine. Il n’y a pas d’indication à une chirurgie carcinologique. Il est recommandé une monochimiothérapie sans platine (doxorubicine liposomale pégylée [DLP], paclitaxel hebdomadaire, topotécan ou gemcitabine) en association avec du bévacizumab si la patiente n’en a pas reçu antérieurement (niveau de preuve 1, grade A). Early relapse (primary or secondary) is defined by relapse of disease less than 6 months before the last infusion of chemotherapy (with a platinum compound). There is no carcinological surgical indication. Disease should be treated with a non-platinum single agent (pegylated liposomal doxorubicin, weekly paclitaxel, gemcitabine or topotecan). Bevacizumab can be added if patients have not already received it (level of proof 1, grade A)

Single-port or Classic Laparoscopy Compared With Laparotomy to Assess the Peritoneal Cancer Index in Primary Advanced Epithelial Ovarian Cancer

International audienceA thorough laparoscopic assessment of the abdominopelvic cavity is a crucial step in the workup of primary advanced epithelial ovarian cancer to decide whether up-front cytoreductive surgery or neoadjuvant chemotherapy is the best option for adequate management. The purpose of our study was to compare single-port laparoscopy (SPL), classic laparoscopy (CL), and laparotomy using the peritoneal cancer index (PCI). Patients treated for Fédération Internationale de Gynécologie et d'Obstétrique stage 3 or 4 epithelial ovarian cancer were included in our study when they underwent a PCI evaluation by laparoscopy followed by laparotomy for cytoreduction. According to the technique used for the "noninvasive" procedure (SPL vs CL), 2 groups were compared retrospectively. The individual records of all patients were reviewed and analyzed. From 2011 to 2014, 21 patients were assessed for PCI by SPL plus laparotomy versus 21 by CL plus laparotomy. The clinicopathological features were similar in both groups (not significant [NS]), except for performance status >0, which was more frequent in the SPL group (39% vs 6%, p = .04). Quotation of PCI was possible for all patients. Nonbrowsing areas marked 3 procedures in the SPL group and 2 procedures in the CL group (NS). The mean PCI score and the score of each region assessed by SPL and CL were comparable with the evaluation by laparotomy (NS). Completeness of cytoreduction was achieved in 78% of cases in both groups (NS). SPL and widely mini-invasive procedures seem to be effective tools compared with laparotomy to adequately assess the resectability of a peritoneal carcinomatosis usin

Safety of adjuvant intensity-modulated postoperative radiation therapy in endometrial cancer: Clinical data and dosimetric parameters according to the International Commission on Radiation Units (ICRU) 83 report

International audienc

Safety of adjuvant intensity-modulated postoperative radiation therapy in endometrial cancer: Clinical data and dosimetric parameters according to the International Commission on Radiation Units (ICRU) 83 report

AimTo report a single-institution experience using postoperative pelvic Intensity Modulation Radiation Therapy (IMRT) using tomotherapy accelerators (TA) in postoperative endometrial cancer (EC) regarding ICRU 83 recommendations.BackgroundIMRT in gynecological malignancies provides excellent dosimetric data, lower rates of adverse events and clinical data similar to historical series.Material and methodsSeventy-six patients with EC were postoperatively treated with adjuvant IMRT using TA. The IMRT dose was 45[[ce:hsp sp="0.25"/]]Gy for patients without positive lymph nodes and Type I histology and 50.4[[ce:hsp sp="0.25"/]]Gy for patients with positive lymph nodes and/or type II histology.ResultsWith a median follow-up of 29 months, the 12- and 24-month Overall Survival (OS) and Disease-Free Survival (DFS) were 96%, 93%, 87%, and 74%, respectively. Age of less than 60 years was associated with better OS (HR: 8.9; CI: 1.1–68) and DFS (HR: 3.5; CI: 1.2–10.2). Patients with Type II and Type I Grade III histology had a worse OS (HR: 3.3; CI: 1.1–11). Five women (6.6%) presented in-field local vaginal recurrence, 2 (2.6%) presented non-in-field vaginal recurrence, 4 (5.2%) presented pelvic node and distant recurrence and 11 (14.4%) presented only distant metastases. One patient stopped radiation treatment due to Grade III acute diarrhea. No Grade III late toxicity was observed. Planning Target Volume (PTV) coverage showed mean D2, D50, D95, and D98 of 51.64–46.23[[ce:hsp sp="0.25"/]]Gy, 49.49–44.97[[ce:hsp sp="0.25"/]]Gy, 48.62–43.96[[ce:hsp sp="0.25"/]]Gy, and 48.47–43.58[[ce:hsp sp="0.25"/]]Gy for patients who received 45 and 50.4[[ce:hsp sp="0.25"/]]Gy, respectively.ConclusionsIMRT with TA in postoperative EC shows excellent conformity and homogeneity of PTV dose. Without Grade III late toxicity, data from this cohort demonstrated the utility of IMRT

Once weekly paclitaxel associated with a fixed dose of oral metronomic cyclophosphamide: a dose-finding phase 1 trial

International audienceBACKGROUND:The primary aim of this trial was to determine the recommended phase II dose (RP2D) of weekly paclitaxel (wP) administered in combination with oral metronomic cyclophosphamide (OMC).METHODS:Patients ≥ 18 years of age with refractory metastatic cancers were eligible if no standard curative measures existed. Paclitaxel was administered IV weekly (D1, D8, D15; D1 = D28) in combination with a fixed dose of OMC (50 mg twice a day). A 3 + 3 design was used for dose escalation of wP (40 to 75 mg/m2) followed by an expansion cohort at RP2D. Dose-limiting toxicity (DLT) was defined over the first 28-day cycle as grade ≥ 3 non-hematological or grade 4 hematological toxicity (NCI-CTCAE v4.0) or any toxicity leading to a dose reduction.RESULTS:In total, 28 pts. (18 in dose-escalation phase and 10 in expansion cohort) were included, and 16/18 pts. enrolled in the dose-escalation phase were evaluable for DLT. DLT occurred in 0/3, 1/6 (neuropathy), 0/3 and 2/4 pts. (hematological toxicity) at doses of 40, 60, 70 and 75 mg/m2 of wP, respectively. The RP2D of wP was 70 mg/m2; 1/10 patients in the expansion phase had a hematological DLT. At RP2D (n = 14), the maximal grade of drug-related adverse event was Gr1 in three patients, Gr2 in six patients, Gr3 in one patient and Gr4 in one patient (no AE in three patients). At RP2D, a partial response was observed in one patient with lung adenocarcinoma.CONCLUSION:The combination of OMC and wP resulted in an acceptable safety profile, warranting further clinical evaluation.TRIAL REGISTRATION:TRN: NCT01374620 ; date of registration: 16 June 2011

Prospective study of serum and aqueous humour anti‐Hsp70.1 IgG antibody levels in ocular toxoplasmosis

International audienc

Efficacy and safety of bevacizumab-containing neoadjuvant therapy followed by interval debulking surgery in advanced ovarian cancer: Results from the ANTHALYA trial

AbstractAimTo investigate whether adding bevacizumab to neoadjuvant carboplatin-paclitaxel (CP) helps achieve optimal debulking, measured by complete resection rate (CRR) at interval debulking surgery (IDS), in patients with initially unresectable International Federation of Gynecology and Obstetrics stage IIIC/IV ovarian, tubal or peritoneal adenocarcinoma.MethodsMulticentre, open-label, non-comparative phase II study. Ninety-five patients randomised (2:1) to receive four cycles of neoadjuvant CP ±3 concomitant cycles of bevacizumab 15 mg/kg (BCP) followed by IDS. Primary objective is to evaluate the CRR at IDS in the BCP group (reference CRR rate defined as 45% CRR). A stopping rule based on bevacizumab-related adverse events (AEs) of special interest was implemented.ResultsIn the BCP group (N = 58), IDS was performed in 40 (69%) patients, of whom 85% had a complete resection. The CRR of this group was therefore 58.6% (34 patients), statistically over pre-defined 45%. The CRR in the CP group was 51.4%: 22 (60%) patients underwent IDS (85% had a complete resection). Grade ≥3 adverse events occurred in 62% of the BCP-treated patients and 63% of the CP-treated patients: mainly blood and lymphatic, gastrointestinal and vascular disorders, without more toxicity with BCP. Postoperative complications (mainly wound, infectious and gastrointestinal complications) occurred in 28% and 36% of the patients, respectively. The pre-specified safety stopping rule was not reached.ConclusionThe primary objective was met as the CRR with BCP was significantly higher than the reference rate. Bevacizumab may be safely added to a preoperative program in patients deemed non-optimally resectable, whatever the final surgical decision. Bevacizumab's role in this setting should be further investigated