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Workshop MicSeaOnMed (EEA GRANT) Blue Biotechnology: from the academy to the entrepreneur sector, Guimarães, Portugal, 24 May 2022

Background: While osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is the standard treatment in patients with advanced non-small-cell lung cancer (NSCLC) with sensitising EGFR and acquired T790M mutations, progression inevitably occurs. The angiogenic pathway is implicated in EGFR TKI resistance. Patients and methods: BOOSTER is an open-label randomised phase II trial investigating the efficacy and safety of combined osimertinib 80 mg daily and bevacizumab 15 mg/kg every 3 weeks, versus osimertinib alone, in patients with EGFR-mutant advanced NSCLC and acquired T790M mutations after failure on previous EGFR TKI therapy. Primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR) and adverse events (AEs). Results: Between May 2017 and February 2019, 155 patients were randomised (combination: 78; osimertinib: 77). At data cut-off of 22 February 2021, median follow-up was 33.8 months [interquartile range (IQR): 26.5-37.6 months] and 129 (83.2%) PFS events were reported in the intention-to-treat population. There was no difference in median PFS between the combination [15.4 months; 95% confidence interval (CI) 9.2-18.0 months] and osimertinib arm (12.3 months; 95% CI 6.2-17.2 months; stratified log-rank P = 0.83), [hazard ratio (HR) = 0.96; 95% CI 0.68-1.37]. Median OS was 24.0 months (95% CI 17.8- 32.1 months) in the combination arm and 24.3 months (95% CI 16.9-37.0 months) in the osimertinib arm (stratified log-rank P = 0.91), (HR = 1.03; 95% CI 0.67-1.56). Exploratory analysis revealed a significant interaction of smoking history with treatment for PFS (adjusted P = 0.0052) with a HR of 0.52 (95% CI 0.30-0.90) for smokers, and 1.47 (95% CI 0.92-2.33) for never smokers. ORR was 55% in both arms and the median time to treatment failure was significantly shorter in the combination than in the osimertinib arm, 8.2 months versus 10.8 months, respectively (P = 0.0074). Safety of osimertinib and bevacizumab was consistent with previous reports with grade >= 3 treatment-related AEs (TRAEs) reported in 47% and 18% of patients on combination and osimertinib alone, respectively. Conclusions: No difference in PFS was observed between osimertinib plus bevacizumab and osimertinib alone. Grade >= 3 TRAEs were more common in patients on combination.

A scientific report based on solid scientific data has been published by AESAN Identifying the most relevant dietary sources of microplastics, knowing the occurrence of the different molecules and polymers and their relevance in terms of exposure will contribute to focus future research projects, regulatory initiatives and monitoring programs. It is the interest of AESAN to promote research on MP and NP in the food supply and contribute to fill the identified knowledge gaps. Toxicokinetic; biomarkers of exposure; toxicity in experimental animals/models like acute toxicity, repeat dose and chronic toxicity; mode of action of the different MP and the observations in humans (Acute and Chronic effects); health based guidance values (dose response models and selection of critical reference points) Assessing the Spanish population dietary exposure to MP should be a challenge for our Food Safety experts and networking among the research groups should be promoted through our national food agencies and EFSA.

[EN] Finding angiogenic prognostic markers in advanced non-small-cell lung cancer is still an unmet medical need. We explored a set of genetic variants in the VEGF-pathway as potential biomarkers to predict clinical outcomes of patients with non-small-cell lung cancer treated with chemotherapy plus bevacizumab. We prospectively analyzed the relationship between VEGF-pathway components with both pathological and prognostic variables in response to chemotherapy plus bevacizumab in 168 patients with non-squamous non-small-cell lung cancer. Circulating levels of VEGF and VEGFR2 and expression of specific endothelial surface markers and single-nucleotide polymorphisms in VEGF-pathway genes were analyzed. The primary clinical endpoint was progression-free survival. Secondary endpoints included overall survival and objective tumor response. VEGFR-1 rs9582036 variants AA/AC were associated with increased progression-free survival (p = 0.012 and p = 0.035, respectively), and with improved overall survival (p = 0.019) with respect to CC allele. Patients with VEGF-A rs3025039 harboring allele TT had also reduced mortality risk (p = 0.049) compared with the CC allele. The VEGF-A rs833061 variant was found to be related with response to treatment, with 61.1% of patients harboring the CC allele achieving partial treatment response. High pre-treatment circulating levels of VEGF-A were associated with shorter progression-free survival (p = 0.036). In conclusion, in this prospective study, genetic variants in VEGFR-1 and VEGF-A and plasma levels of VEGF-A were associated with clinical benefit, progression-free survival, or overall survival in a cohort of advanced non-squamous non-small-cell lung cancer patients receiving chemotherapy plus antiangiogenic therapy., The authors thank Drs. Blanca Piedrafita and Vanessa Marfil at Medical Statistics Consulting for medial writing services. RR also wish to acknowledge the support by the Asociacion Espanola Contra el Cancer (AECC).

Objectives: Multiple reasons for suboptimal treatment of breakthrough cancer pain (BTcP) have been reported in the literature. We aimed to ascertain the perception of physicians on the potential inappropriate use and prescription of rapid-onset opioids (ROOs) for breakthrough cancer pain (BTcP) and the causes thereof.Methods: Observational study based on an online survey addressed to doctors from different specialties (radiation oncology, medical oncology, anesthesia, palliative care and general practitioners) with experience in the management of BTcP in the Spanish public health setting.Results: A total of 114 eligible specialists mainly from radiation oncology (37.7%), medical oncology (24.6%) and pain units (18.4%) participated in the study. Most agreed on important aspects of BTcP management, such as their preference for ROOs or the need for early follow-up after treatment initiation. However, their answers revealed a lack of standardization of BTcP diagnosis. Half of respondents believed that their BTcP patients might misuse ROOs. Physicians polled believed that lack of training in pain management (71.9%) and inadequate BTcP diagnosis and evaluation (66.7%) were the greatest obstacles for prescribing opioids. Specialists also thought that they do not provide the necessary information to patients (51.8%) and caregivers (57.9%) to guarantee the correct use of these drugs.Conclusions: These results are of utmost importance as they highlight the need to increase physicians' awareness of BTcP and its management and the need to improve communication with patients and their caregivers. Our findings also indicate the need for future research on the possible misuse of opioids in BTcP patients and its causes.