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- Arance, Ana, et al.
(author)
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Phase II LEAP-004 Study of Lenvatinib Plus Pembrolizumab for Melanoma With Confirmed Progression on a Programmed Cell Death Protein-1 or Programmed Death Ligand 1 Inhibitor Given as Monotherapy or in Combination.
- 2023
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In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 1527-7755. ; 41:1, s. 75-85
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Journal article (peer-reviewed)abstract
- Effective treatments are needed for melanoma that progresses on inhibitors of programmed cell death protein-1 (PD-1) or its ligand (PD-L1). We conducted the phase II LEAP-004 study to evaluate the combination of the multikinase inhibitor lenvatinib and the PD-1 inhibitor pembrolizumab in this population (ClinicalTrials.gov identifier: NCT03776136).Eligible patients with unresectable stage III-IV melanoma with confirmed progressive disease (PD) within 12 weeks of the last dose of a PD-1/L1 inhibitor given alone or with other therapies, including cytotoxic T-cell lymphocyte-associated antigen 4 (CTLA-4) inhibitors, received lenvatinib 20 mg orally once daily plus ≤ 35 doses of pembrolizumab 200 mg intravenously once every 3 weeks until PD or unacceptable toxicity. The primary end point was objective response rate (ORR) per RECIST, version 1.1, by independent central review.A total of 103 patients were enrolled and treated. The median study follow-up was 15.3 months. ORR in the total population was 21.4% (95% CI, 13.9 to 30.5), with three (2.9%) complete responses and 19 (18.4%) partial responses. The median duration of response was 8.3 months (range, 3.2-15.9+). ORR was 33.3% in the 30 patients with PD on prior anti-PD-1 plus anti-CTLA-4 therapy. The median progression-free survival and overall survival in the total population were 4.2 months (95% CI, 3.8 to 7.1) and 14.0 months (95% CI, 10.8 to not reached), respectively. Grade 3-5 treatment-related adverse events occurred in 47 (45.6%) patients, most commonly hypertension (21.4%); one patient died from a treatment-related event (decreased platelet count).Lenvatinib plus pembrolizumab provides clinically meaningful, durable responses in patients with advanced melanoma with confirmed PD on prior PD-1/L1 inhibitor-based therapy, including those with PD on anti-PD-1 plus anti-CTLA-4 therapy. The safety profile was as expected. These data support lenvatinib plus pembrolizumab as a potential regimen for this population of high unmet need.
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- Fagerholm, F., et al.
(author)
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Cognition in Software Engineering: A Taxonomy and Survey of a Half-Century of Research
- 2022
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In: Acm Computing Surveys. - : Association for Computing Machinery (ACM). - 0360-0300 .- 1557-7341. ; 54:11
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Journal article (peer-reviewed)abstract
- Cognition plays a fundamental role in most software engineering activities. This article provides a taxonomy of cognitive concepts and a survey of the literature since the beginning of the Software Engineering discipline. The taxonomy comprises the top-level concepts of perception, attention, memory, cognitive load, reasoning, cognitive biases, knowledge, social cognition, cognitive control, and errors, and procedures to assess them both qualitatively and quantitatively. The taxonomy provides a useful tool to filter existing studies, classify new studies, and support researchers in getting familiar with a (sub) area. In the literature survey, we systematically collected and analysed 311 scientific papers spanning five decades and classified them using the cognitive concepts from the taxonomy. Our analysis shows that the most developed areas of research correspond to the four life-cycle stages, software requirements, design, construction, and maintenance. Most research is quantitative and focuses on knowledge, cognitive load, memory, and reasoning. Overall, the state of the art appears fragmented when viewed from the perspective of cognition. There is a lack of use of cognitive concepts that would represent a coherent picture of the cognitive processes active in specific tasks. Accordingly, we discuss the research gap in each cognitive concept and provide recommendations for future research.
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