ABSTRACT
Following the results of the PRIMA and PAOLA-1 trials, the most effective maintenance strategy for International Federation of Gynecology and Obstetrics stage III patients is still debated, raising the question which of those two maintenance strategies is the most effective: PARP inhibitors alone or PARP inhibitors in combination with bevacizumab. The ongoing NIRVANA-1 study will try to answer this question by assessing the efficacy and safety of niraparib + bevacizumab in comparison with niraparib alone after adjuvant chemotherapy for completely resected stage III patients. Stratification factors include tumor BRCA status, International Federation of Gynecology and Obstetrics stage (IIIA vs IIIB/IIIC) and the use of hyperthermic intraperitoneal chemotherapy during surgery - within the OVHIPEC-2 trial. The primary end point will be progression-free survival rate at 24 months. Safety, median progression-free survival and overall survival will also be studied.
In many patients with ovarian cancer who are treated with platinum-based chemotherapy after surgery, the tumor comes back several months later. In order to minimize this risk, one treatment approach that has shown promising results is PARP inhibitors. This treatment works by inhibiting cancer cells' ability to repair themselves after DNA damage. One of the PARP inhibitors approved by medical authorities is niraparib, used as a solo therapy after surgery and chemotherapy. Nevertheless, the most effective maintenance strategy for patients in this setting is still debated. In a worldwide clinical trial called NIRVANA-1, researchers are investigating how niraparib would work if combined with another treatment called bevacizumab, which stops the growth of new blood vessels in tumors. Patients who participate in this trial will be randomly assigned to one of two treatment groups: the combination of niraparib + bevacizumab or niraparib by itself. The main purpose of NIRVANA-1 is to understand whether the combination of niraparib and bevacizumab prevents the cancer from returning in patients with completely resected stage III ovarian cancer. The trial will also assess the safety of this combination compared with niraparib alone. At the time of this writing, NIRVANA-1 is open for new patients to join. Sponsored by ARCAGY-GINECO, the NIRVANA-1 trial is currently recruiting patients from France, Spain, Italy, Belgium, Japan and Korea. The duration of the inclusion period is estimated to be around 36 months. The study is registered on ClinicalTrial.gov with registration number NCT05183984.
Subject(s)
Genital Neoplasms, Male , Ovarian Neoplasms , Female , Pregnancy , Male , Humans , Bevacizumab , Poly(ADP-ribose) Polymerase Inhibitors , Chemotherapy, Adjuvant , Carcinoma, Ovarian EpithelialSubject(s)
Brain Neoplasms/mortality , Brain Neoplasms/secondary , Breast Neoplasms/pathology , Breast Neoplasms/therapy , Adult , Aged , Bone Neoplasms/secondary , Brain Neoplasms/pathology , Brain Neoplasms/therapy , Breast Neoplasms/mortality , Chemotherapy, Adjuvant , Female , Humans , Lymphatic Metastasis/pathology , Middle Aged , Prognosis , Receptor, ErbB-2/metabolism , Trastuzumab/therapeutic use , Treatment OutcomeABSTRACT
BACKGROUND: Trastuzumab improves therapeutic outcomes among patients with human epidermal growth factor receptor 2-positive breast cancer (BC). However, it is associated with a risk of treatment-induced cardiotoxicity. The aims of this study were to determine the frequency of trastuzumab-induced cardiotoxicity (TIC) in Tunisian patients, to study the effects of trastuzumab on cardiac biomarkers and echocardiographic parameters using the speckle tracking technique and to identify risk factors of occurrence of TIC. PATIENTS AND METHODS: Fifty women with newly diagnosed human epidermal growth factor receptor 2-positive BC treated with or without anthracycline followed by taxane and trastuzumab were enrolled, from November 2016 to December 2018, to be evaluated every 3 months during trastuzumab treatment (total of 15 mo) using echocardiograms and blood samples. Left ventricular ejection fraction (LVEF) and peak systolic left ventricular longitudinal myocardial strain were calculated. Ultrasensitive troponin I (TNI) and N-terminal pro-B-type natriuretic peptide (NT pro-BNP) were also measured. RESULTS: LVEF decreased from 62±3.12% to 59±3.3% (P=0.005) over 15 months. Seven patients (14%) developed cardiotoxicity, as defined by the European Society of Cardiology; of these patients, 2 (4%) had symptoms of heart failure. Hypertension, left ventricular longitudinal myocardial strain, Log TNI, and NT pro-BNP measured at the completion of anthracyclines were significantly correlated to TIC occurrence. At multivariate analysis, the degree of LVEF decline was the only independent factor correlated to TIC (hazard ratio=2.4; 95% confidence interval=1.2-6.03; P=0.049). This TIC was reversible in 86% of cases. CONCLUSION: In patients with BC treated with trastuzumab, in addition to the evaluation of the LVEF, systolic longitudinal strain, TNI, and NT pro-BNP measured at the completion of anthracyclines are useful in the prediction of subsequent TIC.
Subject(s)
Antineoplastic Agents, Immunological/adverse effects , Breast Neoplasms/drug therapy , Cardiotoxicity , Trastuzumab/adverse effects , Adult , Aged , Breast Neoplasms/genetics , Female , Humans , Middle Aged , Prospective Studies , Receptor, ErbB-2/genetics , Risk Factors , Stroke Volume/drug effects , Tunisia , Ventricular Dysfunction, Left/chemically induced , Ventricular Function, Left/drug effectsABSTRACT
Metastases of ovarian carcinoma to the breast are uncommon. The incidence of ovarian metastasis to the breast ranges from 0.5% to 1.2%. Nevertheless, its detection and distinction from other primaries, especially primary breast carcinoma, is important as treatment and prognosis differ significantly. We report the case of a 38-year-old Tunisian woman with bilateral metastases to breast from ovarian carcinoma. Through a review of literature, we discuss the clinical, radiological and histological characteristics of ovarian metastases to the breast.
Subject(s)
Breast Neoplasms/secondary , Breast/pathology , Carcinoma/pathology , Ovarian Neoplasms/pathology , Adult , Breast Neoplasms/diagnostic imaging , Diagnosis, Differential , Female , Humans , Ovarian Neoplasms/diagnostic imaging , Tomography, X-Ray ComputedABSTRACT
Primary peritoneal serous carcinoma (PPSC) is a rare malignancy of the peritoneum. Clinically and histopathologically, PPSC is similar to serous ovarian papillary carcinoma. Brain metastases (BM) from PPSC are exceedingly rare. We report here a new case of BM two years after complete remission from a PPSC, to make aware physicians about this entity. This case is exceptional; firstly given the rarity of this entity and secondly due to the good response after radiotherapy then systemic chemotherapy with Carboplatin and Paclitaxel.