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PURPOSE Immune checkpoint inhibitors (ICIs) have been demonstrated to improve overall survival (OS) in several tumor types. Durable responses have been reported with these agents in patients with melanoma and lung cancer. We aimed to quantify the proportion of patients who experience durable responses on ICIs and to compare it with other drug classes. PATIENTS AND METHODS We retrieved published phase III randomized trials that included at least one ICI arm in the recurrent and/or metastatic setting. A durable response to treatment was defined as a progression-free survival that exceeded three times the median progression-free survival of the whole population. The proportion of patients who experienced an OS that exceeded two times the median OS of the whole patient population also was estimated. RESULTS Nineteen studies involving 11,640 patients treated in 42 treatment arms (26 ICI and 16 non-ICI arms) were included. The mean proportion of patients who experienced a durable response was 2.3 times higher in those treated with an ICI compared with those treated in the control arms (25% v 11%). Durable responses were more frequent in patients treated with anti–PD-1/PD-L1 agents than in patients treated with anti–CTLA-4 agents (28% v 18%). The mean proportion of patients who had an OS that exceeded two times the median OS was also higher in those treated with ICIs than in those treated in the control arms (30% v 23%). In multivariable analysis, the effects of treatment with anti–PD-1/PD-L1 agents and of first-line treatment were statistically associated with a higher mean proportion of durable responses. CONCLUSION Durable responses were more frequent in patients treated with ICIs, although they also occurred in patients treated with other drug classes.
Purpose: Menopause tends to be associated with an increased risk of obesity and abdominal fat mass (FM) and is associated with lower intestinal species diversity. The aim of this study was to determine the effects of a high-intensity interval training and resistance training (HIIT + RT) program on body composition and intestinal microbiota composition in overweight or obese postmenopausal women. Methods: Participants (n = 17) were randomized in two groups: HIIT + RT group (3 / week, 12 weeks) and control group without any training. Dual-energy X-ray absorptiometry was used to measure whole-body and abdominal/visceral FM and fat-free mass. Intestinal microbiota composition was determined by 16S rRNA gene sequencing at baseline and at the study end, and the diet controlled. Results: Compared with sedentary controls, physical fitness (Maximal Oxygen Consumption, Peak Power Output) increased, total abdominal and visceral FM decreased, and segmental muscle mass increased in the training group. Although the HIIT + RT protocol did not modify α-diversity and taxonomy, it significantly influenced microbiota composition. Moreover, various intestinal microbiota members were correlated with HIIT + RT-induced body composition changes, and baseline microbiota composition predicted the response to the HIIT + RT program. Conclusions: HIIT + RT is an effective modality to reduce abdominal/visceral FM and improve physical capacity in non-dieting overweight or obese postmenopausal women. Training modified intestinal microbiota composition and the response to training seems to depend on the initial microbiota profile. More studies are needed to determine whether microbiota composition could predict the individual training response.
BackgroundHigh throughput molecular screening techniques allow the identification of multiple molecular alterations, some of which are actionable and can be targeted by molecularly targeted agents (MTA). We aimed at evaluating the relevance of using this approach in the frame of Institut Curie Molecular Tumor Board (MTB) to guide patients with cancer to clinical trials with MTAs.Patients and methodsWe included all patients presented at Institut Curie MTB from 4 October 2014 to 31 October 2017. The following information was extracted from the chart: decision to perform tumour profiling, types of molecular analyses, samples used, molecular alterations identified and those which are actionable, and inclusion in a clinical trial with matched MTA.Results736 patients were presented at the MTB. Molecular analyses were performed in 442 patients (60%). Techniques used included next-generation sequencing, comparative genomic hybridisation array and/or other techniques including immunohistochemistry in 78%, 51% and 58% of patients, respectively. Analyses were performed on a fresh frozen biopsy in 91 patients (21%), on archival tissue (fixed or frozen) in 326 patients (74%) and on both archival and fresh frozen biopsy in 25 patients (6%). At least one molecular alteration was identified in 280 analysed patients (63%). An actionable molecular alteration was identified in 207 analysed patients (47%). Forty-five analysed patients (10%) were enrolled in a clinical trial with matched MTA and 29 additional patients were oriented and included in a clinical trial based on a molecular alteration identified prior to the MTB analysis. Median time between date of specimen reception and molecular results was 28 days (range: 5–168).ConclusionsThe implementation of an MTB at Institut Curie enabled the inclusion of 10% of patients into a clinical trial with matched therapy.
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