Hebron University

About: Hebron University is a education organization based out in Hebron, Palestinian Territory. It is known for research contribution in the topics: Population & Cancer. The organization has 2714 authors who have published 4180 publications receiving 163736 citations.

Molecular prescreening to select patient population in early clinical trials

Abstract: The efficacy of targeted therapies in patient populations selected for treatment on the basis of the molecular features of their tumours is shifting the current focus of treatment to biomarker-driven clinical trials. Phase I trials provide an arena for early hypothesis testing, examining not only safety and toxicity, but also target engagement, biologically effective dosages, and the appropriate patient population. In this Perspectives article, we describe this new trend in early drug development, establishing the different approaches for building a pre-screening programme in an academic institution that is involved in early drug development. Our experience establishing the phase I programme at Vall d'Hebron serves as an example of how these approaches can be integrated in ongoing trials, and we believe these considerations will help others to implement similar programmes in their institutions.

Oral fingolimod (FTY720) in relapsing multiple sclerosis: impact on health-related quality of life in a phase II study.

Abstract: Background: Health-related quality of life (HRQoL) worsens with multiple sclerosis (MS) relapses and disease progression. Common symptoms including depression and fatigue may contribute to poor HRQ...

Capturing Hyperprogressive Disease with Immune-Checkpoint Inhibitors Using RECIST 1.1 Criteria.

Abstract: Purpose: Most hyperprogression disease (HPD) definitions are based on tumor growth rate (TGR). However, there is still no consensus on how to evaluate this phenomenon. Patients and Methods: We investigated two independent cohorts of patients with advanced solid tumors treated in phase I trials with (i) programmed cell death 1 (PD-1)/PD-L1 antibodies in monotherapy or combination and (ii) targeted agents (TA) in unapproved indications. A Response Evaluation Criteria in Solid Tumors (RECIST) 1.1–based definition of hyperprogression was developed. The primary endpoint was the assessment of the rate of HPD in patients treated with ICIs or TAs using both criteria (RECIST and TGR) and the impact on overall survival (OS) in patients who achieved PD as best response. Results: Among 270 evaluable patients treated with PD-1/PD-L1 inhibitors, 29 PD-1/PD-L1–treated patients (10.7%) had HPD by RECIST definition. This group had a significantly lower OS (median of 5.23 months; 95% CI, 3.97–6.45) when compared with the non-HPD progressor group (median, 7.33 months; 95% CI, 4.53–10.12; HR = 1.73, 95% CI, 1.05–2.85; P = 0.04). In a subset of 221 evaluable patients, 14 (6.3%) were categorized as HPD using TGR criteria, differences in median OS (mOS) between this group (mOS 4.2 months; 95% IC, 2.07–6.33) and non-HPD progressors (n = 44) by TGR criteria (mOS 6.27 months; 95% CI, 3.88–8.67) were not statistically significant (HR 1.4, 95% IC, 0.70–2.77; P = 0.346). Among 239 evaluable patients treated with TAs, 26 (10.9%) were classified as having HPD by RECIST and 14 using TGR criteria in a subset of patients. No differences in OS were observed between HPD and non-HPD progressors treated with TAs. Conclusions: HPD measured by TGR or by RECIST was observed in both cohorts of patients; however, in our series, there was an impact on survival only in the immune-checkpoint inhibitor cohort when evaluated by RECIST. We propose a new way to capture HPD using RECIST criteria that is intuitive and easy to use in daily clinical practice.

Treating cancer's kinase 'addiction'.

Abstract: When the tyrosine kinase inhibitor imatinib (Gleevec) was found to induce high remission rates in patients with chronic myeloid leukemia, this was hailed as a success for targeted tumor therapy. Since then, the repertoire of cancer types that respond to such inhibitors has expanded and researchers are beginning to grapple with the problem of acquired drug resistance. The activating kinase mutations targeted by these drugs can be viewed as the Achilles heel of cancer—they promote malignant progression, yet can turn cancer into a therapeutically exploitable disease.