ORCID Profile
0000-0002-1533-3815
Current Organisations
CHUM
,
Université de Montréal
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Publisher: Elsevier BV
Date: 08-2018
DOI: 10.1016/J.SCITOTENV.2018.03.106
Abstract: Anthropogenic effects of urban density have altered natural ecosystems. Such changes include eutrophication of freshwater and adjoining coastal habitats, and increased levels of inorganic nutrients and pollutants into waterways. In Australia, these changes are intensified by large-scale ocean-atmospheric events, leading to considerable abiotic stress on the natural flora and fauna. Bacterial communities in marine sediments from Moreton Bay (South East Queensland, Australia) were examined in order to assess the impact of rainfall changes, chemical pollution, and subsequent abiotic stress on living organisms within a marine ecosystem. Sediments were collected during the wet and dry seasons and analyzed using bacterial metagenomics and community metabolomics techniques. Physicochemical data were also analyzed to account for biological variance that may be due to non-rainfall-based abiotic stresses. Wet-dry seasonality was the dominant control on bacterial community structure and metabolic function. Changes in the availability of nutrients, organic matter and light appeared to be the major seasonal stressors. In contrast, urban and industrial pollutants appeared to be minor stressors at the sites s led. During the wet season, the bacterial community composition reflected organisms that utilize biogeochemical pathways with fast kinetics, such as aerobic metabolism, direct assimilation of inorganic compounds, and primary production. The transition to the dry season saw the bacterial community composition shift towards organisms that utilize more complex organic energy sources, such as carbohydrates and fatty acids, and anaerobic redox processes.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 20-07-2022
DOI: 10.1200/JCO.21.02198
Abstract: The phase III KEYNOTE-048 (ClinicalTrials.gov identifier: NCT02358031 ) trial of pembrolizumab in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) included planned efficacy analyses in the total population and in participants with programmed death ligand-1 (PD-L1) combined positive score (CPS) ≥ 1 and CPS ≥ 20. To further characterize the predictive value of PD-L1 expression on outcome, we conducted efficacy analyses in the PD-L1 CPS 1 and CPS 1-19 subgroups in KEYNOTE-048. Participants with R/M HNSCC and no prior systemic therapy for R/M disease were randomly assigned 1:1:1 to pembrolizumab, pembrolizumab-chemotherapy, or cetuximab-chemotherapy. Post hoc efficacy analyses of the PD-L1 CPS 1 and CPS 1-19 subgroups were performed. Of 882 participants enrolled, 128 had PD-L1 CPS 1 and 373 had CPS 1-19. For pembrolizumab versus cetuximab-chemotherapy, the median overall survival was 7.9 versus 11.3 months in the PD-L1 CPS 1 subgroup (hazard ratio [HR], 1.51 [95% CI, 0.96 to 2.37]) and 10.8 versus 10.1 months in the CPS 1-19 subgroup (HR, 0.86 [95% CI, 0.66 to 1.12]). For pembrolizumab-chemotherapy versus cetuximab-chemotherapy, the median overall survival was 11.3 versus 10.7 months in the PD-L1 CPS 1 subgroup (HR, 1.21 [95% CI, 0.76 to 1.94]) and 12.7 versus 9.9 months in the CPS 1-19 subgroup (HR, 0.71 [95% CI, 0.54 to 0.94]). Increased efficacy of pembrolizumab or pembrolizumab-chemotherapy was observed with increasing PD-L1 expression. PD-L1 CPS 1 subgroup analysis was limited by small participant numbers. Results from the PD-L1 CPS 1-19 subgroup support previous findings of treatment benefit with pembrolizumab monotherapy and pembrolizumab-chemotherapy in patients with PD-L1 CPS ≥ 1 tumors. Although PD-L1 expression is informative, exploration of additional predictive biomarkers is needed for low PD-L1–expressing HNSCC.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 02-2023
DOI: 10.1200/JCO.21.02508
Abstract: Pembrolizumab and pembrolizumab-chemotherapy demonstrated efficacy in recurrent/metastatic head and neck squamous cell carcinoma in KEYNOTE-048. Post hoc analysis of long-term efficacy and progression-free survival on next-line therapy (PFS2) is presented. Patients were randomly assigned (1:1:1) to pembrolizumab, pembrolizumab-chemotherapy, or cetuximab-chemotherapy. Efficacy was evaluated in programmed death ligand 1 (PD-L1) combined positive score (CPS) ≥ 20, CPS ≥ 1, and total populations, with no multiplicity or alpha adjustment. The median study follow-up was 45.0 months (interquartile range, 41.0-49.2 n = 882). At data cutoff (February 18, 2020), overall survival improved with pembrolizumab in the PD-L1 CPS ≥ 20 (hazard ratio [HR], 0.61 95% CI, 0.46 to 0.81) and CPS ≥ 1 populations (HR, 0.74 95% CI, 0.61 to 0.89) and was noninferior in the total population (HR, 0.81 95% CI, 0.68 to 0.97). Overall survival improved with pembrolizumab-chemotherapy in the PD-L1 CPS ≥ 20 (HR, 0.62 95% CI, 0.46 to 0.84), CPS ≥ 1 (HR, 0.64 95% CI, 0.53 to 0.78), and total (HR, 0.71 95% CI, 0.59 to 0.85) populations. The objective response rate on second-course pembrolizumab was 27.3% (3 of 11). PFS2 improved with pembrolizumab in the PD-L1 CPS ≥ 20 (HR, 0.64 95% CI, 0.48 to 0.84) and CPS ≥ 1 (HR, 0.79 95% CI, 0.66 to 0.95) populations and with pembrolizumab-chemotherapy in the PD-L1 CPS ≥ 20 (HR, 0.64 95% CI, 0.48 to 0.86), CPS ≥ 1 (HR, 0.66 95% CI, 0.55 to 0.81), and total (HR, 0.73 95% CI, 0.61 to 0.88) populations. PFS2 was similar after pembrolizumab and longer after pembrolizumab-chemotherapy on next-line taxanes and shorter after pembrolizumab and similar after pembrolizumab-chemotherapy on next-line nontaxanes. With a 4-year follow-up, first-line pembrolizumab and pembrolizumab-chemotherapy continued to demonstrate survival benefit versus cetuximab-chemotherapy in recurrent/metastatic head and neck squamous cell carcinoma. Patients responded well to subsequent treatment after pembrolizumab-based therapy.
No related grants have been discovered for Denis Soulières.