AIO Studien gGmbH

Patients with lung cancer under treatment have been associated with a high risk of COVID-19 infection and potentially worse outcome, but real-world data on patient-reported outcomes (PROs) are rare. We assess patients' characteristics and PROs before and during the COVID-19 pandemic in an advanced non-small cell lung cancer (NSCLC) cohort in Germany. Patients with locally advanced or metastatic NSCLC from the prospective, multicentre, observational CRISP Registry (NCT02622581) were categorised as pre-pandemic (March 2019 to Feb 2020, n = 1621) and pandemic (March 2020 to Feb 2021, n = 1317). From baseline to month 15, patients' health-related quality of life (HRQoL) was assessed by FACT-L, anxiety and depression by PHQ-4. Association of pandemic status with time to deterioration (TTD) in QoL scales adjusted for potential covariates was estimated using Cox modelling. PROs were documented for 1166 patients (72%) in the pre-pandemic, 979 (74%) in the pandemic group. Almost 60% of patients were male, median age was 66 years, comorbidities occurred in 85%. Regarding HRQoL, mean-change-from-baseline plots hardly differed between both samples. Approximately 15%-21% of patients reported anxiety, about 19%-27% signs of depression. For the pandemic group, TTD was slightly, but statistically significantly, worse for the physical well-being-FACT-G subscale (HR 1.15 [95%CI 1.02-1.30]) and the anxiety-GAD-2 subscale (HR 1.14 [95%CI 1.01-1.29]). These prospectively collected real-world data provide valuable insights into PROs before and during the COVID-19 pandemic in advanced NSCLC. For the patients, the pandemic seemed to be less of a burden than the disease itself, as there was a considerable proportion of patients with anxiety and depression in both groups.

Simple SummaryThere is a need to better understand the effectiveness of new treatments, such as the recently approved nivolumab, in patients with locally advanced or metastatic non-small cell lung cancer in clinical practice. This study aims to report the characteristics and outcomes of 2784 patients with locally advanced or metastatic non-small cell lung cancer receiving nivolumab in second-line or later in France (ESME-AMLC) and Germany (CRISP) between 2015 and 2020. Two-year survival rates were 26.7% in patients with tumors with squamous histology and 32.8% in patients with non-squamous/others histologies in ESME-AMLC, and 20.9% and 18.9%, respectively, in CRISP. Poorer performance score and shorter duration from the previous line of therapy initiation were significantly associated with shorter treatment duration with nivolumab and overall survival. These real-world data provide insight into the characteristics of patients receiving nivolumab in France and Germany and confirm the efficacy of nivolumab previously observed in clinical trials.This study reports characteristics and outcomes in patients with locally advanced or metastatic non-small cell lung cancer (aNSCLC) receiving nivolumab in second-line or later (2L+) in France and Germany between 2015 and 2020. Patients with aNSCLC (stage IIIB–C/IV) receiving nivolumab in 2L+ were included from the retrospective Epidemiological Strategy and Medical Economics of Advanced and Metastatic Lung Cancer cohort (ESME-AMLC, France; 2015–2019) and Clinical Research platform Into molecular testing, treatment and outcome of non-Small cell lung carcinoma Patients (CRISP, Germany; 2016–2020). Overall, 2262 ESME-AMLC and 522 CRISP patients were included. Median treatment duration (95% confidence intervals) was 2.8 months (2.5–3.2) in squamous and 2.5 months (2.3–2.8) in non-squamous/others patients in ESME-AMLC, and 2.3 months (1.4–3.1) and 2.3 months (2.0–2.8), respectively in CRISP. One-year and two-year overall survival (OS) were 47.2% and 26.7% in squamous and 50.8% and 32.8% in non-squamous/others patients in ESME-AMLC, and 43.1% and 20.9%, and 37.7% and 18.9%, respectively in CRISP. Poorer performance score and shorter time from start of previous line of therapy initiation were significantly associated with shorter treatment duration and OS. This study confirms, in real-world clinical databases, the efficacy of nivolumab previously observed in clinical trials.

Aberrant neuronal network activity likely resulting from disturbed interactions of excitatory and inhibitory systems may be a major cause of cognitive deficits in neuropsychiatric diseases, like within the spectrum of schizophrenic phenotypes. In particular, the synchrony and pattern of oscillatory brain activity appears to be disturbed within limbic networks, e.g. between prefrontal cortex and hippocampus. In a rat model of maternal immune activation (MIA), we compared the acute effects of deep brain stimulation within either medial prefrontal cortex or ventral hippocampus with the effects of repetitive transcranial magnetic stimulation (rTMS), using the intermittent theta-burst protocol (iTBS), on oscillatory activity within limbic structures. Simultaneous local field potential recordings were made from medial prefrontal cortex, ventral hippocampus, nucleus accumbens and rostral part of ventral tegmental area before and after deep brain stimulation in anaesthetized rats previously (~3h) treated with sham or verum rTMS. We found a waxing and waning pattern of theta and gamma activity in all structures which was less synchronous in particular between medial prefrontal cortex and ventral hippocampus in MIA offspring. Deep brain stimulation in medial prefrontal cortex and pre-treatment with iTBS-rTMS partly improved this pattern. Gamma-theta cross-frequency coupling was stronger in MIA offspring and could partly be reduced by deep brain stimulation in medial prefrontal cortex. We can confirm aberrant limbic network activity in a rat MIA model, and at least acute normalizing effects of the neuromodulatory methods. It has to be proven whether these procedures can have chronic effects suitable for therapeutic purposes.

Abstract Background: Elderly patients represent a major fraction of non-small cell lung cancer (NSCLC) patients in routine clinical practice, but they are still underrepresented in clinical trials. In particular, data regarding efficacy and safety in frail or elderly patients with respect to immunotherapy are lacking. Importantly, immunosenescence in elderly patients might interfere with activities of immune-modulating drugs such as PD-1/PD-L1 inhibitors. Thus, there is an urgent need to assess safety and efficacy of such inhibitors in this group. Methods/design: In this prospective, open label, treatment stratified, and randomized phase II study, 200 patients with stage IV NSCLC amenable at least to single-agent chemotherapy (CT). Eligible patients must be 70 years or older and/or “frail” (Charlson Comorbidity Index >1) or have a restricted performance status (Eastern Cooperative Oncology Group, ECOG >1). Patients are stratified according to modified Cancer and Age Research Group (CARG) score:”fit” patients are allocated to combination CT (carboplatin/ nab -paclitaxel), “less fit” patients receive single-agent CT (gemcitabine or vinorelbine). After allocation to strata, patients are randomized 1:1 to receive either 4 cycles of CT or 2 cycles of CT followed by 2 cycles of durvalumab and subsequent maintenance treatment with durvalumab every 4 weeks. The primary endpoint is the rate of treatment related grade III/IV adverse events (Common Terminology Criteria for Adverse Events, CTCAE V4.03). As secondary endpoints, progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1, response rate (RR), overall survival (OS), descriptive subgroup analyses according to PD-L1 expression, and quality of life are addressed. Geriatric screening assessments and functional tests will be performed to complete the phenotyping of a potential “frail” and “elderly” patient cohort. The trial is accompanied by a biomaterial repository to explore potential biomarkers. Discussion: The DURATION trial will prospectively investigate the safety and tolerability of anti-PD-L1 treatment with durvalumab after chemotherapy in elderly and frail patients and thereby provide new insights into the effect of PD-L1 blockade and the impact of immunosenescence in this cohort of patients.