Quality of Life With Pembrolizumab for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma: KEYNOTE-040

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) affects health-related quality of life (HRQoL); few treatments have demonstrated clinically meaningful HRQoL benefit. KEYNOTE-040 evaluated pembrolizumab versus standard of care (SOC) in patients with recurrent/metastatic (R/M) HNSCC whose disease recurred/progressed after platinum-containing regimen. METHODS: Patients received pembrolizumab 200\u2009mg or SOC (methotrexate, docetaxel, or cetuximab). Exploratory HRQoL analyses used European Organisation for Research and Treatment of Cancer (EORTC) 30 quality-of-life, EORTC 35-question quality-of-life head and neck cancer-specific module, and EuroQoL 5-dimensions questionnaires. RESULTS: HRQoL population comprised 469 patients (pembrolizumab=241, SOC=228). HRQoL compliance for patients on study at week 15 was 75.3% (116/154) for pembrolizumab and 74.6% (85/114) for SOC. Median time to deterioration in global health status (GHS)/QoL score was 4.8 months and 2.8 months, respectively (HR, 0.79; 95% CI: 0.59, 1.05). At week 15, GHS/QoL scores were stable for pembrolizumab (least squares mean [LSM], 0.39; 95% CI: -3.00, 3.78) but worsened for SOC (LSM, -5.86; 95% CI: -9.68, -2.04); LSM between-group difference was 6.25 points (95% CI: 1.32, 11.18; nominal 2-sided P=.01). Greater difference in LSM score for GHS/QoL occurred with pembrolizumab versus docetaxel (10.23; 95% CI: 3.15, 17.30) compared with pembrolizumab versus methotrexate (6.21; 95% CI: -4.57, 16.99) or pembrolizumab versus cetuximab (-1.44; 95% CI: -11.43, 8.56). Pembrolizumab-treated patients had stable functioning and symptoms at week 15, with no notable differences from SOC. CONCLUSIONS: GHS/QoL was stable with pembrolizumab but declined with SOC in patients at week 15, supporting the clinically meaningful benefit of pembrolizumab in R/M HNSCC

Distribution of costameric proteins in the diaphragm of patients with chronic obstructive pulmonary disease.

Contains fulltext : 50857.pdf (publisher's version ) (Closed access)BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with an increased load on the diaphragm. Increased (eccentric) loading has been shown to result in disturbances in the cytoskeleton. OBJECTIVES: We hypothesized that due to a continuous overload of the diaphragm in COPD patients, distinct alterations in the membrane-associated cytoskeleton occur, especially in the costameres. METHODS: Diaphragm biopsies from 7 COPD patients (forced expiratory volume in 1 s 62 +/- 3% predicted) and 5 non-COPD patients (forced expiratory volume in 1 s 105 +/- 6% predicted) were obtained. Cryosections of these biopsies were stained with antibodies against the costameric proteins of the focal adhesion complex (vinculin, talin and integrin-beta(1)), the dystroglycan complex (dystrophin and beta-dystroglycan) and the spectrin-based membrane cytoskeleton (beta-spectrin). Furthermore, in these cryosections, the basal membrane protein laminin was stained. RESULTS: We found no differences in the distribution and staining intensity of the costameric proteins of the focal adhesion complex, the dystroglycan complex and the spectrin-based membrane cytoskeleton in the diaphragm between the COPD and the non-COPD patients. Furthermore, no differences were observed in the expression of laminin in the diaphragm between COPD and non-COPD patients. CONCLUSIONS: These results indicate that the increased loading to which the diaphragm is exposed in COPD does not result in disturbances in expression of the costameric system and histological damage of the sarcolemma