Background: In the phase III IMpassion130 trial, combining atezolizumab with first-line nanoparticle albumin-boundpaclitaxel for advanced triple-negative breast cancer (aTNBC) showed a statistically significant progression-free survival (PFS) benefit in the intention-to-treat (ITT) and programmed death-ligand 1 (PD-L1)-positive populations, and a clinically meaningful overall survival (OS) effect in PD-L1-positive aTNBC. The phase III KEYNOTE-355 trial adding pembrolizumab to chemotherapy for aTNBC showed similar PFS effects. IMpassion131 evaluated first-line atezolizumabepaclitaxel in aTNBC. Patients and methods: Eligible patients [no prior systemic therapy or 12 months since (neo)adjuvant chemotherapy] were randomised 2:1 to atezolizumab 840 mg or placebo (days 1, 15), both with paclitaxel 90 mg/m 2 (days 1, 8, 15), every 28 days until disease progression or unacceptable toxicity. Stratification factors were tumour PD-L1 status, prior taxane, liver metastases and geographical region. The primary endpoint was investigator-assessed PFS, tested hierarchically first in the PD-L1-positive [immune cell expression 1%, VENTANA PD-L1 (SP142) assay] population, and then in the ITT population. OS was a secondary endpoint. Results: Of 651 randomised patients, 45% had PD-L1-positive aTNBC. At the primary PFS analysis, adding atezolizumab to paclitaxel did not improve investigator-assessed PFS in the PD-L1-positive population [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.60-1.12; P ¼ 0.20; median PFS 6.0 months with atezolizumabepaclitaxel versus 5.7 months with placeboepaclitaxel]. In the PD-L1-positive population, atezolizumabepaclitaxel was associated with more favourable unconfirmed best overall response rate (63% versus 55% with placeboepaclitaxel) and median duration of response (7.2 versus 5.5 months, respectively). Final OS results showed no difference between arms (HR 1.11, 95% CI 0.76-1.64; median 22.1 months with atezolizumabepaclitaxel versus 28.3 months with placeboe paclitaxel in the PD-L1-positive population). Results in the ITT population were consistent with the PD-L1-positive population. The safety profile was consistent with known effects of each study drug. Conclusion: Combining atezolizumab with paclitaxel did not improve PFS or OS versus paclitaxel alone. ClinicalTrials.gov: NCT03125902.
Chronic low back pain (CLBP) is associated with a number of costly disability-related outcomes. It has received increasing attention from qualitative researchers studying its consequences for personal, social, and health care experiences. As research questions and methods diversify, there is a growing need to integrate findings emerging from these studies. A meta-ethnography was carried out to synthesise the findings of 38 separate qualitative articles published on the subjective experience of CLBP between 1994 and 2011. Studies were identified following a literature search and quality appraisal. Four themes were proposed after a process of translating the meaning of text extracts from the findings sections across all the articles. The themes referred to the undermining influence of pain, its disempowering impact on all levels, unsatisfying relationships with health care professionals, and learning to live with the pain. The findings are dominated by wide-ranging distress and loss but also acknowledge self-determination and resilience. Implications of the meta-ethnography for clinicians and future qualitative research are outlined, including the need to study relatively unexamined facets of subjective experience such as illness trajectory and social identity.
Patient expectations from these treatments are often unrealistic. Although objective responses are low, active palliation with chemotherapy is associated with substantive improvement in patients' emotional function and global QL, with overall costs that seem relatively modest.
Recent investigators have attempted to manipulate mood in the laboratory by having subjects read a series of self-referent mood statements and have reported significant changes in affect. The present study was designed to assess the contribution of demand characteristics to the outcomes of these experiments. In addition to having subjects read elating, neutral, or depressing self-referent statements or instructing them to act elated or depressed, the present investigators included two counter-demand groups in which subjects read the elation or depression statements but were told to expect to feel the reverse of what the statements implied. The results indicated that demand characteristics do indeed contribute to mood shifts engendered by this technique, but that the shifts are not merely artifactual.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.