In the OlympiAD study, olaparib was shown to improve progression-free survival compared with chemotherapy treatment of physician’s choice (TPC) in patients with a germline BRCA1 and/or BRCA2 mutation ...(BRCAm) and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (mBC). We now report the planned final overall survival (OS) results, and describe the most common adverse events (AEs) to better understand olaparib tolerability in this population.
OlympiAD, a Phase III, randomized, controlled, open-label study (NCT02000622), enrolled patients with a germline BRCAm and HER2-negative mBC who had received ≤2 lines of chemotherapy for mBC. Patients were randomized to olaparib tablets (300mg bid) or predeclared TPC (capecitabine, vinorelbine, or eribulin). OS and safety were secondary end points.
A total of 205 patients were randomized to olaparib and 97 to TPC. At 64% data maturity, median OS was 19.3months with olaparib versus 17.1months with TPC (HR 0.90, 95% CI 0.66–1.23; P = 0.513); median follow-up was 25.3 and 26.3months, respectively. HR for OS with olaparib versus TPC in prespecified subgroups were: prior chemotherapy for mBC no (first-line setting): 0.51, 95% CI 0.29–0.90; yes (second/third-line): 1.13, 0.79–1.64; receptor status (triple negative: 0.93, 0.62–1.43; hormone receptor positive: 0.86, 0.55–1.36); prior platinum (yes: 0.83, 0.49–1.45; no: 0.91, 0.64–1.33). Adverse events during olaparib treatment were generally low grade and manageable by supportive treatment or dose modification. There was a low rate of treatment discontinuation (4.9%), and the risk of developing anemia did not increase with extended olaparib exposure.
While there was no statistically significant improvement in OS with olaparib compared to TPC, there was the possibility of meaningful OS benefit among patients who had not received chemotherapy for metastatic disease. Olaparib was generally well-tolerated, with no evidence of cumulative toxicity during extended exposure.
The article by Bonet (BJOG ……..) is not the first paper to challenge the benefit of the partogram and the 1cm/hour rate of progress. Although the conclusion is simple the evidence and methodology ...used is not convincing to those that use the partogram on a daily basis. The use of the partogram and normal progress of labour at ≥1 cm/hour are an integral part of the philosophy of Active Management Labour (AML) which has been practiced at the National Maternity Hospital, Dublin for the last 55 years. This philosophy which at best is often misunderstood and ignored and at worst misrepresented and misused has been shown to be associated with low caesarean section rates (CSR) in spontaneous labour and also reduce CSR when studied in randomized trials. This article is protected by copyright. All rights reserved.
Next-generation sequencing (NGS) allows sequencing of a high number of nucleotides in a short time frame at an affordable cost. While this technology has been widely implemented, there are no ...recommendations from scientific societies about its use in oncology practice. The European Society for Medical Oncology (ESMO) is proposing three levels of recommendations for the use of NGS. Based on the current evidence, ESMO recommends routine use of NGS on tumour samples in advanced non-squamous non-small-cell lung cancer (NSCLC), prostate cancers, ovarian cancers and cholangiocarcinoma. In these tumours, large multigene panels could be used if they add acceptable extra cost compared with small panels. In colon cancers, NGS could be an alternative to PCR. In addition, based on the KN158 trial and considering that patients with endometrial and small-cell lung cancers should have broad access to anti-programmed cell death 1 (anti-PD1) antibodies, it is recommended to test tumour mutational burden (TMB) in cervical cancers, well- and moderately-differentiated neuroendocrine tumours, salivary cancers, thyroid cancers and vulvar cancers, as TMB-high predicted response to pembrolizumab in these cancers.
Outside the indications of multigene panels, and considering that the use of large panels of genes could lead to few clinically meaningful responders, ESMO acknowledges that a patient and a doctor could decide together to order a large panel of genes, pending no extra cost for the public health care system and if the patient is informed about the low likelihood of benefit. ESMO recommends that the use of off-label drugs matched to genomics is done only if an access programme and a procedure of decision has been developed at the national or regional level. Finally, ESMO recommends that clinical research centres develop multigene sequencing as a tool to screen patients eligible for clinical trials and to accelerate drug development, and prospectively capture the data that could further inform how to optimise the use of this technology.
•ESMO recommends the use of tumour multigene NGS in NSCLC, cholangiocarcinoma, prostate and ovarian cancers.•It is recommended to test TMB in well- and moderately-differentiated neuroendocrine tumours (NETs), cervical, salivary, thyroid and vulvar cancers.•Academic research centres should perform multigene NGS as part of their missions to enable access to innovative treatments.•A large panel of genes could be ordered, considering the benefit for the patient and the cost for the public health care system.
•This ESMO Clinical Practice Guideline provides key recommendations and algorithms for managing metastatic breast cancer.•It covers diagnosis, staging, risk assessment, treatment, disease monitoring, ...palliative care and the patient perspective.•ESMO-MCBS and ESCAT scores are given to describe the levels of evidence for treatment choices.•The authors comprise an international expert group, with recommendations based on available evidence and expert opinion.•In clinical practice, all recommendations provided need to be discussed with patients in a shared decision-making approach.
Abstract Objectives The purpose of this study was to explore the diagnostic usefulness of hybrid cardiac magnetic resonance (CMR) and positron emission tomography (PET) using 18F-fluorodeoxyglucose ...(FDG) for active cardiac sarcoidosis. Background Active cardiac sarcoidosis (aCS) is underdiagnosed and has a high mortality. Methods Patients with clinical suspicion of aCS underwent hybrid CMR/PET with late gadolinium enhancement (LGE) and FDG to assess the pattern of injury and disease activity, respectively. Patients were categorized visually as magnetic resonance (MR)+PET+ (characteristic LGE aligning exactly with increased FDG uptake), MR+PET− (characteristic LGE but no increased FDG), MR−PET− (neither characteristic LGE nor increased FDG), and MR−PET+ (increased FDG uptake in absence of characteristic LGE) and further characterized as aCS+ (MR+PET+) or aCS− (MR+PET−, MR−PET−, MR−PET+). FDG uptake was quantified using maximum target-to-normal-myocardium ratio and the net uptake rate ( K i ) from dynamic Patlak analysis. Receiver operating characteristic methods were used to identify imaging biomarkers for aCS. FDG PET was assessed using computed tomography/PET in 19 control subjects with healthy myocardium. Results A total of 25 patients (12 males; 54.9 ± 9.8 years of age) were recruited prospectively; 8 were MR+PET+, suggestive of aCS; 1 was MR+PET−, consistent with inactive cardiac sarcoidosis; and 8 were MR−PET−, with no imaging evidence of cardiac sarcoidosis. Eight patients were MR−PET+ (6 with global myocardial FDG uptake, 2 with focal-on-diffuse uptake); they demonstrated distinct K i values and hyperintense maximum standardized uptake value compared with MR+PET+ patients. Similar hyperintense patterns of global (n = 9) and focal-on-diffuse (n = 2) FDG uptake were also observed in control patients, suggesting physiological myocardial uptake. Maximum target-to-normal-myocardium ratio values were higher in the aCS+ group (p < 0.001), demonstrating an area under the curve of 0.98 on receiver operating characteristic analysis for the detection of aCS, with an optimal maximum target-to-normal myocardium ratio threshold of 1.2 (Youden index: 0.94). Conclusions CMR/PET imaging holds major promise for the diagnosis of aCS, providing incremental information about both the pattern of injury and disease activity in a single scan. (In Vivo Molecular Imaging MRI of Atherothrombotic Lesions; NCT01418313 )
Digital game-based and gamified technologies hold much promise to promote the development of learners' conceptual knowledge. This efficacy study used desktop virtual reality (dVR) to investigate how ...the place-based digital gameful learning experience (DGLE) "Watershed Explorers", implemented as a curriculum enhancement activity, impacted students' watershed literacy as well as their attitudes towards playing and learning during dVR gameplay. Thirty-five middle school students completed a pretest-posttest content assessment measuring watershed literacy, a motivation to play with a dVR game survey, and a perception of learning with dVR games survey. Results showed that using "Watershed Explorers" as a curriculum enhancement activity can positively impact learning, especially middle school students' ability to identify their own local watershed and its connections to the ocean. Most participants perceived this DGLE as a helpful and engaging type of learning technology that can promote stimulating ways of presenting content materials and make school learning more interesting. Implications for the design of future iterations of "Watershed Explorers" to enhance learning are also discussed.
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