OBJECTIVE:High blood eosinophil counts (BECs) are associated with increased asthma exacerbation risk. Studies show anti-IL-5/5R biologics meaningfully reduce BEC; however, there are limited data describing the real-world effects of anti-IgE and anti-IL-4R biologics on BECs. This analysis aimed to describe BECs before and after initiation of different biologics in a real-world cohort of patients with severe asthma (SA). METHODS:CHRONICLE (NCT03373045) was an observational study of subspecialist-treated adults with SA in the US receiving biologics or maintenance systemic corticosteroids or whose disease was persistently uncontrolled on high-dosage inhaled corticosteroids and additional controllers. This analysis included patients enrolled between February 2018 and November 2023 who initiated omalizumab, mepolizumab, benralizumab, or dupilumab treatment. Patients' highest BECs in the 12 months before, 2 to <12 months after, and ≥12 months after biologic initiation were evaluated. RESULTS:In total, 323 of the 3912 enrolled patients met the inclusion criteria, of whom 61 received omalizumab, 80 received mepolizumab, 118 received benralizumab, and 64 received dupilumab. Patients treated with anti-IL-5/5R biologics (mepolizumab, benralizumab) had higher pretreatment BECs that were reduced at both 2 to <12 months and ≥12 months following initiation. Conversely, patients treated with anti-IL-4R (dupilumab) or anti-IgE (omalizumab) biologics had lower pretreatment BECs that were slightly reduced 2 to <12 months following initiation but increased ≥12 months following initiation. CONCLUSION:Among US subspecialist-treated patients with SA, those treated with biologics that do not block or reduce IL-5/5R may experience an increase in BEC over time.

Purpose:There are limited recent data assessing all-cause mortality for US patients with severe asthma. This descriptive analysis evaluated all-cause mortality in a real-world cohort of US adults with subspecialist-treated severe asthma, examining patient characteristics among those who died, physician-reported primary causes of death, and associations with treatment class. Patients and Methods:CHRONICLE (NCT03373045) was an observational study of US adults (aged ≥18 years) with subspecialist-treated severe asthma, enrolled from February 2018 to October 2024. Patients met at least one of the following criteria: ongoing FDA-approved monoclonal antibody therapy, maintenance systemic corticosteroids (mSCS) for ≥50% of the prior year, or persistently uncontrolled asthma despite high-dosage inhaled corticosteroids and additional controllers. All-cause mortality was assessed descriptively, overall and by treatment class at time of death. Investigators reported primary causes of death and COVID-19 involvement. Treatment class exposure was calculated by the cumulative days on biologics and/or mSCS. Results:Among 4366 enrolled patients, mean age was 54.7 years; 69.7% were female, 73.1% were White, and 18.6% were Black. Over 14,758 person-years of observation, 130 deaths occurred (3.0%), yielding a mortality of 8.8 (95% confidence interval: 7.4, 10.5) per 1000 person-years. Cardiovascular disease was the leading cause of death (25.4%), followed by cancer (13.1%) and asthma (1.5%). COVID-19 contributed to 8.5% of deaths. Observed associations for all-cause mortality ranged from 6.8 per 1000 person-years in patients who were receiving biologics without mSCS to 31.6 per 1000 person-years in those receiving mSCS without biologics. Conclusion:US adults with subspecialist-treated severe asthma have an increased risk of all-cause mortality, especially those patients receiving mSCS. These findings highlight the importance of identifying mortality risks and limiting the use of mSCS whenever possible while supporting further research into the relationship between severe asthma and cardiovascular disease.

Thymic stromal lymphopoietin (TSLP) is a key upstream epithelial cytokine and its over-expression is associated with inflammation leading to immune dysfunction, epithelial barrier disruption, and tissue remodeling. TSLP is implicated in the pathogenesis of multiple atopic diseases including asthma, chronic rhinosinusitis with nasal polyps and eosinophilic esophagitis (EoE). EoE is a chronic, type 2 (T2) inflammatory disease linked to a delayed-type hypersensitivity response to food antigens and characterized by eosinophil-predominant mucosal inflammation and esophageal dysfunction. TSLP expression and TSLP-mediated T2 inflammatory activity is elevated in esophageal biopsies in patients with active EoE compared with patients with inactive EoE and healthy individuals. In phase 3 clinical trials, a monoclonal antibody against TSLP, tezepelumab, has shown significant improvements in clinical outcomes compared with placebo in other atopic conditions that have a shared T2 inflammatory disease pathology and epithelial remodeling pathway with EoE such as asthma and chronic rhinosinusitis with nasal polyps. In this review, we present evidence of TSLP involvement in mediating and exacerbating EoE pathology and discuss how targeting TSLP activity could be a viable therapeutic option for EoE treatment.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory disorder of the sinonasal mucosa, predominantly characterized by epithelial dysfunction and chronic heterogeneous mucosal inflammation. CRSwNP and asthma are common comorbidities with overlapping pathophysiology, epithelial impairment, and activation of downstream type 2 inflammation. Thymic stromal lymphopoietin (TSLP) is an epithelial cytokine that sits at the top of the immunological cascade and initiates and amplifies type 2-dependent and -independent inflammatory responses. Although the role of TSLP in asthma has been well described, the role of TSLP in CRSwNP has yet to be comprehensively outlined. This review examines the evidence for TSLP as a key factor in CRSwNP pathogenesis. We explore what is known about TSLP expression patterns within the sinonasal mucosa, finding that TSLP expression is increased in patients with CRSwNP compared with healthy patients, and in eosinophilic- versus non-eosinophilic CRSwNP. We discuss the impact of environmental triggers and genetic factors on TSLP expression and activity, as well as other upstream regulators of TSLP signaling. We then consider the known mechanisms and effects of TSLP signaling on the recruitment and activation of various immune and structural cell types in CRSwNP. Finally, we consider the available evidence on the therapeutic potential of targeting TSLP signaling for the treatment of CRSwNP and discuss ongoing trials of promising therapeutic candidates.

Airway inflammation, a hallmark feature of asthma, drives many canonical features of the disease, including airflow limitation, mucus plugging, airway remodeling, and hyperresponsiveness. The T2 inflammatory paradigm is firmly established as the dominant mechanism of asthma pathogenesis, largely due to the success of inhaled corticosteroids and biologic therapies targeting components of the T2 pathway, including IL-4, IL-5, IL-13, and thymic stromal lymphopoietin (TSLP). However, up to 30% of patients may lack signatures of meaningful T2 inflammation (ie, T2 low). In T2-low asthma patients, T2 inflammation may be masked due to anti-inflammatory treatments or may be highly variable depending on exposure to common asthma triggers such as allergens, respiratory infections, and smoke or pollution. The epithelium and epithelial cytokines (TSLP, IL-33) are increasingly recognized as upstream drivers of canonical T2 pathways and as modulators of various effector cells, including mast cells, eosinophils, and neutrophils, which impact the pathological manifestations of airway smooth muscle hypertrophy, hypercontractility, and airway hyperresponsiveness. Approved biologics for severe asthma target several distinct mechanisms of action, leading to differential effects on the spectrum of T2 inflammation, inflammatory biomarkers, and treatment efficacy (reducing asthma exacerbations, improving lung function, and diminishing symptoms). The approved anti-asthma biologics primarily target T2 immune pathways, with little evidence suggesting a benefit of targeting non-T2 asthma-associated mediators. Indeed, many negative results challenge current assumptions about the etiology of non-T2 asthma and raise doubts about the viability of targeting popular alternative inflammatory pathways, such as T17. Novel data have emerged from the use of biologics to treat various inflammatory mediators and have furthered our understanding of pathogenic mechanisms that drive asthma. This review discusses inflammatory pathways that contribute to asthma, quantitatively outlines effects of available biologics on biomarkers, and summarizes data and challenges from clinical trials that address non-T2 mechanisms of asthma.

Introduction (contexte de la recherche) Tézépélumab, un anticorps monoclonal humain, bloque l’activité de la lymphopoïétine stromale thymique (TSLP). Les études de phase 2b PATHWAY et de phase 3 NAVIGATOR ont démontré que tézépélumab réduit les exacerbations, améliore la fonction pulmonaire, le contrôle de l’asthme et la qualité de vie par rapport au placebo chez les patients asthmatiques sévères non contrôlés. Objectif Cette analyse exploratoire préspécifiée a évalué l’efficacité du tézépélumab chez les patients issus de ces deux études, en fonction de leur éligibilité au traitement par dupilumab (conformément aux conditions de prescription européennes). Méthodes PATHWAY et NAVIGATOR étaient des études multicentriques, randomisées, en double aveugle, contrôlées contre placebo, de méthodologies similaires. Les patients (12 à 80ans) inclus dans cette analyse poolée ont reçu tézépélumab 210mg ou un placebo par voie sous-cutanée toutes les 4 semaines (sem) pendant 52 sem. L’éligibilité au dupilumab était définie par un asthme T2 insuffisamment contrôlé avec, à l’inclusion, une valeur de la fraction expirée du monoxyde d’azote (FeNO) ≥25 ppb et/ou un taux d’éosinophiles sanguins (EOS)≥150 cellules/μL, malgré un traitement par fortes doses de corticoïdes inhalés et un autre traitement de fond. Le taux annualisé d’exacerbations d’asthme (TAEA) sur 52 sem et la variation du volume expiratoire maximal par seconde (VEMS) pré-bronchodilatateur (BD) entre l’inclusion et la semaine 52 ont été évalués chez les patients éligibles au dupilumab. Résultats Au total, 800 patients (395 sous tézépélumab et 405 sous placebo) étaient éligibles au dupilumab. Chez ces patients, tézépélumab a réduit de 66 % (IC95 % : 58–73) le TAEA sur 52 sem par rapport au placebo et a permis des améliorations du VEMS pré-BD plus importantes qu’avec le placebo (différence par rapport à l’inclusion de 0,20 [IC95 % : 0,14–0,26] L). Conclusions Tézépélumab a réduit les exacerbations et amélioré le VEMS pré-BD par rapport au placebo chez les patients éligibles au dupilumab. Ces résultats confirment les bénéfices de tézépélumab chez les patients asthmatiques sévères T2 non contrôlés, y compris ceux présentant des taux de FeNO≥25 ppb et/ou d’EOS≥150 cellules/μL et éligibles au dupilumab.

Tézépélumab, un anticorps monoclonal humain, bloque l'activité de la lymphopoïétine stromale thymique (TSLP). Les études de phase 2b PATHWAY (NCT02054130) et de phase 3 NAVIGATOR (NCT03347279) ont démontré que tézépélumab réduit les exacerbations, améliore la fonction pulmonaire, le contrôle de l'asthme et la qualité de vie par rapport au placebo chez les patients asthmatiques sévères non contrôlés. Cette analyse exploratoire pré-spécifiée vise à évaluer l'efficacité du tézépélumab chez les patients issus des études PATHWAY et NAVIGATOR, en fonction de leur éligibilité au traitement par dupilumab (conformément aux conditions de prescription européennes). Les études PATHWAY et NAVIGATOR étaient des études multicentriques, randomisées, en double aveugle, contrôlées contre placebo, de méthodologies similaires. Les patients (âgés de 12 à 80 ans) asthmatiques sévères non contrôlés inclus dans cette analyse poolée ont reçu tézépélumab 210 mg ou un placebo par voie sous cutanée toutes les 4 semaines pendant 52 semaines. Pour cette analyse exploratoire, l'éligibilité au dupilumab était définie par un asthme de type 2 insuffisamment contrôlé avec, à l'inclusion, une valeur de la fraction expirée du monoxyde d'azote (FeNO) ≥ 25 ppb et/ou un taux d'éosinophiles sanguins ≥ 150 cellules/μL, malgré un traitement par fortes doses de corticostéroïdes inhalés et un autre traitement de fond. Le taux annualisé d'exacerbations d'asthme (TAEA) sur 52 semaines et la variation du volume expiratoire maximal par seconde (VEMS) pré-bronchodilatateur (BD) entre l'inclusion et la semaine 52 ont été évalués chez les patients éligibles au dupilumab. Au total, 800 patients (395 sous tézépélumab et 405 sous placebo) étaient éligibles au dupilumab. Chez ces patients, tézépélumab a réduit de 66% (IC95%: 58–73; Fig. 1) le TAEA sur 52 semaines par rapport au placebo. À la semaine 52, les améliorations du VEMS pré-BD étaient plus importantes avec tézépélumab qu'avec le placebo chez les patients éligibles au dupilumab (variation moyenne des moindres carrés par rapport à l'inclusion, 0,28 L vs 0,08 L; différence de 0,20 [IC95%: 0,14–0,26] L). Des améliorations cliniquement significatives du VEMS pré-BD ont été observées dès la semaine 4 (premier point de mesure dans PATHWAY) chez les patients traités par tézépélumab. Tézépélumab a réduit les exacerbations et amélioré le VEMS pré-BD par rapport au placebo chez les patients éligibles au dupilumab. Ces résultats confirment les bénéfices de tézépélumab chez les patients atteints d'asthme sévère T2 et non contrôlés, y compris ceux présentant des taux, à l'inclusion, de FeNO≥25 ppb et/ou d'éosinophiles sanguins ≥ 150 cellules/μL et éligibles à un traitement par dupilumab.

Tezepelumab blocks the activity of thymic stromal lymphopoietin, an epithelial cytokine implicated in the pathogenesis of asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). In a previous analysis, tezepelumab improved asthma and rhinosinusitis symptoms compared with placebo in patients with severe, uncontrolled asthma and a history of CRSwNP in the 2 years before randomization in the NAVIGATOR study. This post hoc analysis of patients with a CRSwNP diagnosis at any time before randomization in NAVIGATOR enabled domain and symptom-specific analyses of Sino-Nasal Outcome Test (SNOT)-22 outcomes. Patients (aged 12–80 years) with severe, uncontrolled asthma were randomized to tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. SNOT-22 total, domain, and item scores were assessed in patients with a history of CRSwNP. Annualized asthma exacerbation rate (primary efficacy outcome), pre-bronchodilator forced expiratory volume in 1 s, and Asthma Control Questionnaire-6, Asthma Quality of Life Questionnaire (standardized) for patients 12 years and older, and Asthma Symptom Diary scores were also assessed in patients with and without a history of CRSwNP. Of 1059 patients with severe asthma, 165 (15.6 https://classic.clinicaltrials.gov/ct2/show/NCT03347279 ).

Purpose: Younger age of asthma onset (AAO) has been associated with an allergic phenotype, whereas eosinophilic phenotypes have been associated with older AAO. In randomized trials, biologic efficacy among adults with severe asthma (SA) has varied by age at asthma onset. To determine whether these associations observed in trials apply to real-world outcomes, this study examined biologic effectiveness by AAO and biologic class in a large, real-world cohort. Patients and methods: CHRONICLE is an ongoing, real-world study of US adults with subspecialist-treated SA receiving biologics, maintenance corticosteroids, or who are uncontrolled on high-dosage inhaled corticosteroids with additional controllers. Patients enrolled between February 2018 and February 2022 who initiated a biologic for SA and had complete data for analysis were included. A locally estimated scatterplot smoothing (LOESS) analysis was used to plot the relationship between percentage exacer- bation rate reduction and AAO by biologic class. Results: Of 578 patients with complete data, 198, 149, and 231 were diagnosed with asthma at age <18, 18-39, and >= 40 years, respectively. Across subgroups, patients were predominantly White (72-78%), female (67-73%), and commercially insured (54-71%). In the LOESS analysis, exacerbation rate reductions were similar for anti-IgE and anti-IL-5/5R and anti-IL-4R subgroups with younger AAO, but the exacerbation rate reduction diminished for patients with older AAO receiving anti-IgE therapy, particularly with asthma onset age >= 40 years. Conclusion: Clinicians should consider age of onset in biologic treatment decisions, given reduced effectiveness of omalizumab in patients with asthma onset at age >= 40 years.

La rhinosinusite chronique avec polypes nasaux est une maladie inflammatoire des voies aériennes supérieures et une comorbidité fréquente dans l'asthme sévère. Le « Sino-Nasal Outcome Test (SNOT)-22 » est une méthode validée pour évaluer la sévérité des symptômes et l'impact de la rhinosinusite sur la qualité de vie (HRQoL). Cette analyse post-hoc a évalué l'efficacité du tézépélumab via les scores du SNOT-22, total et par domaine, chez les patients avec des antécédents de polypose nasale (PN) issus de l'étude de phase 3 NAVIGATOR (NCT03347279). NAVIGATOR était une étude multicentrique, randomisée, en double aveugle, contrôlée par placebo. Les patients (âgés de 12 à 80 ans) asthmatiques sévères non contrôlés ont été randomisés 1 : 1 pour recevoir tézépélumab 210 mg ou un placebo par voie sous-cutanée toutes les 4 semaines pendant 52 semaines. Les variations des scores du SNOT-22, total et par domaine, ont été évalués entre l'inclusion dans l'étude et la semaine 52 chez les patients présentant des antécédents de PN. Le SNOT-22 comprend 22 items, chacun noté de 0 (aucun problème) à 5 (problème très sévère) et classé en cinq domaines : nasal (8 items), oreille/facial (4 items), sommeil (4 items), fonction (3 items) et émotion (3 items). Les scores de chaque domaine ont été calculés comme étant la moyenne des scores des items d'un domaine donné (de 0 à 5). Le score total du SNOT-22 varie de 0 (aucun impact) à 110 (impact maximal) ; la différence minimale cliniquement importante (MCID) est de 8,9. Au total, 165 patients présentant des antécédents de PN ont été randomisés pour recevoir tézépélumab (n = 90) ou un placebo (n = 75). À l'inclusion, les scores totaux moyens du SNOT-22 étaient similaires chez les patients avec des antécédents de PN et recevant tézépélumab ou le placebo (49,6 [n = 69] et 49,3 [n = 62], respectivement). Les scores moyens du SNOT-22 par domaine, à l'inclusion, étaient également similaires entre les groupes traités par tézépélumab et le placebo (nasal : 2,7, 2,6 ; oreille/facial : 1,5, 1,4 ; sommeil : 2,4, 2,5 ; fonction : 2,3, 2,5 ; émotion : 1,8, 1,8, respectivement). La variation des scores totaux du SNOT-22 entre l'inclusion et la semaine 52 était de −21,29 pour tézépélumab et de −10,21 pour le placebo (différence moyenne des moindres carrés [LS], −11,08 [intervalle de confiance à 95 % (IC95 %) : −17,80, −4,35]) (Fig. 1). Tézépélumab a numériquement réduit le score de chaque domaine du SNOT-22 entre l'inclusion et la semaine 52 par rapport au placebo. Tézépélumab a permis d'améliorer les symptômes cliniquement significatifs de la rhinosinusite et la qualité de vie sur 52 semaines par rapport au placebo évalué par les scores du SNOT-22. Des réductions numériques ont été observées dans tous les domaines, les plus importantes étant observées dans le domaine nasal, sommeil et fonction. Ces résultats démontrent l'efficacité de tézépélumab pour améliorer les symptômes de rhinosinusite chez les patients asthmatiques sévères non contrôlés avec des antécédents de PN.

Introduction In the phase 2b PATHWAY (NCT02054130) and phase 3 NAVIGATOR (NCT03347279) studies, tezepelumab reduced inflammatory biomarker levels (blood eosinophil count [BEC], fractional exhaled nitric oxide [FeNO] and serum total immunoglobulin E [IgE]) at week 52 compared with placebo in patients with severe, uncontrolled asthma. This post hoc pooled analysis of PATHWAY and NAVIGATOR assessed the effects of tezepelumab on inflammatory biomarker levels over the continuum of biomarker levels at baseline. Methods PATHWAY and NAVIGATOR were multicenter, randomized, double-blind, placebo-controlled, parallel-group, 52-week studies with similar designs. Included patients (12–80 years old) received tezepelumab 210 mg or placebo subcutaneously every 4 weeks. Among tezepelumab recipients, the absolute percentage changes from baseline to week 52 in BEC and levels of FeNO and serum total IgE were visualized using locally estimated regression and smoothing scatterplots. Results Among the 665 tezepelumab recipients included, median (range) biomarker levels at baseline were 260 (0–3650) cells/µL for BEC, 28 (4–235) ppb for FeNO and 177.1 (1.5–12 823.2) IU/mL for serum total IgE. At week 52, tezepelumab reduced inflammatory biomarker levels over the continuum of baseline biomarker levels; a greater magnitude of effect was observed with increasing levels the respective biomarker, especially BEC and FeNO, at baseline (Figure). Conclusion Across multiple biomarkers, tezepelumab treatment led to consistently greater reductions in biomarker levels with increasing levels of the respective biomarker at baseline.

Patients with moderate-to-severe asthma frequently have comorbid nasal polyps (NP), which are associated with an increased disease burden and may benefit from biologic treatment. This analysis summarized annualized asthma exacerbation rate (AAER) reductions and changes in Sino-Nasal Outcome Test (SNOT)-22 scores from randomized, placebo-controlled studies of biologic treatment in patients with moderate-to-severe, uncontrolled asthma and a history of comorbid NP.

In the PATHWAY (NCT02054130) and NAVIGATOR (NCT03347279) studies, tezepelumab reduced the annualized asthma exacerbation rate (AAER) over 52 weeks versus placebo among patients with severe, uncontrolled asthma. The efficacy of tezepelumab in patients with fungal sensitization at baseline was evaluated using pooled data from PATHWAY and NAVIGATOR.

BACKGROUND: Understanding the implementation of key guideline recommendations is critical for managing severe asthma (SA) in the treatment of uncontrolled disease. OBJECTIVE: To assess specialist visits and medication escalation in US patients with SA after events indicating uncontrolled disease (EUD) and associations with health outcomes and social disparity indicators. METHODS: Patients with SA appearing in administrative claims data spanning 2015 to 2020 were indexed hierarchically on asthma-related EUD, including hospitalizations, emergency department visits with systemic corticosteroid treatment, or outpatient visits with systemic corticosteroid treatment. Patients with SA without EUD served as controls. Eligibility included age 12 or greater, 12 months enrollment before and after index, no biologic use, and no other major respiratory disease during the pre-period. Escalation of care in the form of specialist visits and medication escalation, health care resource use, costs, and disease exacerbations were assessed during follow-up. RESULTS: We identi fi ed 180,736 patients with SA (90,368 uncontrolled and 90,368 controls). Between 35% and 51% of patients with SA with an EUD had no specialist visit or medication escalation. Follow-up exacerbations ranged from 51% to 4% across EUD cohorts, compared with 13% in controls. Among uncontrolled patients with SA who were Black or Hispanic/Latino, 41% and 38%, respectively, had no specialist visit or medication escalation after EUD, compared with 33% of non-Hispanic White patients. CONCLUSIONS: A substantial proportion of uncontrolled patients with SA had no evidence of specialist visits or medication escalation after uncontrolled disease, and there was a clear relationship between uncontrolled disease and subsequent health care resource use and exacerbations. Findings highlight the need for improved guideline-based care delivery to patients with SA, particularly for those facing social disparities. (c) 2024 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/). (J Allergy Clin Immunol Pract 2024;12:1775-82)

Background: Acquired resistance limits long-term epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) efficacy in patients with EGFR mutation-positive non-small-cell lung cancer (NSCLC) in whom anti-programmed death-ligand 1 (PD-L1) efficacy is also limited. We hypothesized that combining atezolizumab with erlotinib could enhance antitumor immunity and extend efficacy in these patients.Patients and methods: This open-label phase Ib trial was conducted in adults aged >18 years who had advanced, unresectable NSCLC. Stage 1 (safety evaluation) enrolled EGFR TKI-naive patients regardless of EGFR status. Stage 2 (expansion) enrolled patients with EGFR-mutant NSCLC treated with <1 prior non-EGFR TKI therapy. Patients received 150 mg erlotinib orally once daily. After a 7-day erlotinib run-in, atezolizumab 1200 mg was administered intravenously every 3 weeks. The primary endpoint was the safety and tolerability of the combination in all patients; secondary endpoints included antitumor activity per RECIST 1.1 in stage 2 patients.Results: At the data cut-off on 7 May 2020, 28 patients (8 in stage 1, 20 in stage 2) were assessable for safety. No dose -limiting toxicities or grade 4 or 5 treatment-related adverse events occurred. Grade 3 treatment-related adverse events occurred in 46% of patients; the most common were increased alanine aminotransferase, diarrhea, pyrexia, and rash (each in 7% of patients). Serious adverse events occurred in 50% of patients. Pneumonitis (grade 1) was reported in a single patient (4%). The objective response rate was 75% [95% confidence interval (CI) 50.9% to 91.3%]), median response duration was 18.9 months (95% CI 9.5-40.5 months), median progression-free survival was 15.4 months (95% CI 8.4-39.0 months), and median overall survival was not estimable (NE) (95% CI 34.6-NE).Conclusions: Atezolizumab combined with erlotinib demonstrated a tolerable safety profile and encouraging, durable clinical activity in patients with advanced EGFR mutation-positive NSCLC.

Background: In the phase 3 NAVIGATOR study (NCT03347279), tezepelumab gradually decreased serum total immunoglobulin (Ig)E levels in patients with severe, uncontrolled asthma over 52 weeks. In the phase 3 DESTINATION study (NCT03706079), this reduction continued to end of treatment (EOT; week 104). Objective: To assess serum total IgE during the off-treatment extended follow-up (EFU) in DESTINATION, following tezepelumab cessation. Methods: Patients (12–80 years) who completed NAVIGATOR could enrol in DESTINATION, a multicentre, randomized, placebo-controlled, double-blind, extension study. Patients previously randomized to tezepelumab continued treatment (tezepelumab only; 210 mg every 4 weeks). Those previously randomized to placebo were re-randomized 1:1 to placebo (placebo only) or tezepelumab. At EOT, eligible patients could enter a 36-week off-treatment EFU. Change in serum total IgE over time was assessed. Results: Overall, 569 patients entered the EFU. Mean baseline serum total IgE was 586.18 and 625.19 IU/mL for the tezepelumab only and placebo only subgroups. After tezepelumab cessation, serum total IgE remained low; there was a partial increase from week 122, but levels remained below baseline (Figure). Conclusion: Serum total IgE levels reductions achieved with tezepelumab during NAVIGATOR and DESTINATION were maintained for 36 weeks after tezepelumab cessation, suggesting a maintained immunological effect.