Bayer (Italy)

Despite the availability of various anti-vascular endothelial growth factor (anti-VEGF) therapies for diabetic macular edema (DME), high treatment burden remains a significant issue in many European countries, including Italy. This burden impacts healthcare costs, clinic capacities, and patient adherence. Aflibercept 8mg was developed to reduce treatment burden by requiring only three monthly injections before allowing extended dosing intervals up to 6months, without compromising efficacy and safety. This analysis aimed to evaluate the efficacy, safety, and treatment burden of aflibercept 8mg regimens compared to other anti-VEGF options (aflibercept 2mg, ranibizumab 0.5mg, faricimab 6mg, brolucizumab 6mg, and bevacizumab 1.25mg) in Italy. A systematic literature review identified randomised controlled trials of anti-VEGF therapies for DME with a 2-year follow-up. This informed a Bayesian network meta-analysis (NMA) assessing efficacy, safety, and treatment burden. A cost-minimisation analysis (CMA) was conducted from the perspective of the Italian National Health System over a 2-year horizon. The NMA, involving nine studies, showed no significant differences in best-corrected visual acuity, anatomical outcomes, and safety between aflibercept 8mg and the other anti-VEGF agents. Aflibercept 8mg required fewer injections than the comparators, with a mean of 9.3 injections over 2years for T&E (Q12) and 8.4 for T&E (Q16) regimens. Economically, aflibercept 8mg was the least costly licensed and reimbursed anti-VEGF in Italy. Aflibercept 8mg may be the most advantageous anti-VEGF option for reducing treatment burden in Italian patients with DME, benefiting healthcare providers, clinics, and the healthcare system. Aflibercept 8mg offers comparable efficacy and safety to other anti-VEGF therapies, with fewer injections and potentially lower overall costs.

Additional therapeutic options are needed for patients with lung cancer with HER2 activating mutations, including exon 20 insertions. Sevabertinib shows activity against ERBB2-encoded HER2 exon 20 insertions in preclinical models of lung cancer, corroborated by early data from a phase 1/2 clinical trial.

TPS3185 Background: Human epidermal growth factor receptor 2 ( HER2 ) gene mutations occur in approximately 3.5% of solid tumors, with a frequency varying from less than 1% to 9%, depending on the tumor type. BAY 2927088 is an oral, reversible tyrosine kinase inhibitor that potently inhibits HER2 and mutant epidermal growth factor receptor and has shown clinical benefit based on preliminary evidence from the Phase I/II SOHO-01 trial in patients with HER2 -mutant non-small cell lung cancer (NSCLC; PL04.03 presented at IASLC 2024 World Conference on Lung Cancer), an indication for which the FDA has granted Breakthrough Designation. Here we introduce the panSOHO trial evaluating the efficacy and safety of BAY 2927088 in patients with unresectable, locally advanced or metastatic solid tumors with HER2 -activating mutations. Methods: panSOHO is a Phase II, open-label, multicenter, multinational, single-arm basket trial of BAY 2927088 in patients with unresectable or metastatic solid tumors with HER2 -activating mutations (NCT06760819), and will be conducted in the USA, Europe, and the Asia-Pacific region. Eligibility criteria include patients aged ≥18 years with: documented histologically or cytologically confirmed, locally advanced or metastatic solid tumor cancer (colorectal, biliary tract, bladder and urothelial tract, cervical, endometrial, or other solid tumor); documented activating HER2 mutation; ≥1 measurable lesion per RECIST v1.1; and previous standard therapy or no satisfactory alternative treatment options. Key exclusion criteria include primary diagnosis of NSCLC, treatment with a HER2 tyrosine kinase inhibitor, untreated active brain metastases, and leptomeningeal disease. Overall, 111 eligible patients will receive BAY 2927088 p.o. 20 mg twice daily in 3-week cycles until disease progression, unacceptable toxicity, or study withdrawal. The primary outcome is BAY 2927088 efficacy on objective response rate per RECIST v1.1 as assessed by blinded independent central review (BICR). Secondary outcomes include BAY 2927088 efficacy on time to response, duration of response, disease control rate, and progression-free survival per RECIST v1.1 by BICR, and overall survival, and BAY 2927088 safety and tolerability. Impact of BAY 2927088 on patient quality of life will be evaluated by EORTC QLQ-C30. Enrollment is open. Clinical trial information: NCT06760819 .

This study aimed to describe the characteristics, treatment patterns, adverse events (AEs), and clinical outcomes of patients starting steroidal mineralocorticoid receptor antagonists (sMRAs) in real-world settings. The RELICS study, complementing the survey-based RELICS-PS study, was a retrospective cohort study conducted using the Healthcare Integrated Research Database (HIRD®), a single-payer healthcare database with medical and pharmacy claims from health insurance plans across the United States. A cohort of adults initiating sMRAs from January 2016 to June 2021 was divided into six subgroups: three mutually exclusive heart failure (HF) subgroups, two mutually exclusive chronic kidney disease (CKD) subgroups, and "all other patients" subgroup, which included those without documented HF or CKD. Outcomes assessed from the first sMRA fill until death, health-plan disenrollment, or June 2022 (whichever came first) included analysis of treatment patterns, AEs, and clinical outcomes. Factors associated with sMRA discontinuation were evaluated with multivariate logistic regression. Of the 224,100 sMRA initiators identified, 76.4% did not have documented HF or CKD (ie, "all other patients" subgroup). This subgroup was younger and primarily female. Across all initiators, 72.3% were nonadherent, and 73.0% discontinued treatment within a median of 90 days of initiation. Of these discontinuers, 44.2% restarted treatment within a median of 91 days of discontinuation. Factors decreasing odds of discontinuation across most subgroups included a higher comorbidity burden, use of other cardiovascular medications, and cardiologist prescribing. These findings were consistent across subgroups. AEs and clinical outcomes varied across subgroups in line with baseline comorbidity profiles. Patients with a higher comorbidity burden, such as those with both CKD and T2D rather than CKD alone, experienced worse outcomes. High rates of treatment discontinuation and subsequent restart were observed across all subgroups, implying fluctuating sMRA use. However, heightened cardiovascular risk may decrease the odds of discontinuation.

Larotrectinib, a first-in-class, highly selective tropomyosin receptor kinase (TRK) inhibitor, has demonstrated efficacy in adult and pediatric patients with various solid tumors harboring NTRK gene fusions. This subset analysis focuses on the efficacy and safety of larotrectinib in an expanded cohort of adult patients with TRK fusion sarcomas. Patients (≥18years old) with sarcomas harboring NTRK gene fusions were identified from three clinical trials. Patients received larotrectinib 100mg orally twice daily. Response was investigator-assessed per RECIST v1.1. Data cutoff was July 20, 2021. At the data cutoff, 36 adult patients with TRK fusion sarcomas had initiated larotrectinib therapy: two (6%) patients had bone sarcomas, four (11%) had gastrointestinal stromal tumors, and 30 (83%) had soft tissue sarcomas. All patients were evaluable for response and demonstrated an objective response rate of 58% (95% confidence interval, 41-74). Patients responded well to larotrectinib regardless of number of prior lines of therapy. Adverse events (AEs) were mostly grade 1/2. Grade 3 treatment-emergent AEs (TEAEs) occurred in 15 (42%) patients. There were no grade 4 TEAEs. Two grade 5 TEAEs were reported, neither of which were considered related to larotrectinib. Four (11%) patients permanently discontinued treatment due to TEAEs. Larotrectinib demonstrated robust and durable responses, extended survival benefit, and a favorable safety profile in adult patients with TRK fusion sarcomas with longer follow-up. These results continue to demonstrate that testing for NTRK gene fusions should be incorporated into the clinical management of adult patients with various types of sarcomas. Tropomyosin receptor kinase (TRK) fusion proteins result from translocations involving the NTRK gene and cause cancer in a range of tumor types. Larotrectinib is an agent that specifically targets TRK fusion proteins and is approved for the treatment of patients with TRK fusion cancer. This study looked at how well larotrectinib worked in adult patients with sarcomas caused by TRK fusion proteins. Over half of patients had a durable response to larotrectinib, with no unexpected side effects. These results show that larotrectinib is safe and effective in adult patients with TRK fusion sarcomas.

Simple SummaryAlthough the use of antimicrobials and the related selection of antimicrobial-resistant (AMR) pathogens are recognized worldwide, limited or no information is available on the effect of the antibiotic treatment on the genetic structure as well as the dissemination and persistence of plasmids carrying AMR genetic determinants. This is of particular interest for bacterial pathogens like Avian Pathogenic Escherica coli (APEC), which have the potential to persist and be transmitted from broilers to humans through the food chain as well as for their AMR genetic determinants, which have the potential to be mobilized and spread. With a genomic approach, results of the present study revealed that during the enrofloxacin treatment of broilers, initial strains of extraintestinal E. coli disappeared, being substituted by new clones. Plasmid-mediated fluoroquinolone resistance did not appear to disseminate or persist among observed genomes, confirming that QRDR mutations rather than plasmids are the main drivers of quinolone resistance. Interestingly, plasmids carrying other AMR genes than quinolone-determinant ones were disseminated and persistent since they were found in different clones both before and after the treatment. The persistence of plasmids without a direct antimicrobial selective pressure, if confirmed with further studies, might give insights on the so-called plasmid paradox.The aim of the present study was to investigate the genetic diversity and antimicrobial resistance (AMR) of E. coli during enrofloxacin therapy in broilers affected by colisepticemia. Three unrelated farms with ongoing colibacillosis outbreaks were sampled at day 1 before treatment and at days 5, 10 and 24 post-treatment. A total of 179 E. coli isolates were collected from extraintestinal organs and submitted to serotyping, PFGE and the minimum inhibitory concentration (MIC) against enrofloxacin. PFGE clusters shifted from 3–6 at D1 to 10–16 at D5, D10 and D24, suggesting an increased population diversity after the treatment. The majority of strains belonged to NT or O78 and to ST117 or ST23. PFGE results were confirmed with SNP calling: no persistent isolates were identified. An increase in resistance to fluoroquinolones in E. coli isolates was observed along the treatment. Resistome analyses revealed qnrB19 and qnrS1 genes along with mutations in the gyrA, parC and parE genes. Interestingly, despite a fluoroquinolone selective pressure, qnr-carrying plasmids did not persist. On the contrary, two conjugative AMR plasmid clusters (AB233 and AA474) harboring AMR genes other than qnr were persistent since they were identified in both D1 and D10 genomes in two farms. Further studies should be performed in order to confirm plasmid persistence not associated (in vivo) to antimicrobial selective pressure.