Daily Respiratory Research Analysis
Analyzed 92 papers and selected 3 impactful papers.
Summary
Analyzed 92 papers and selected 3 impactful articles.
Selected Articles
1. Sacituzumab tirumotecan plus pembrolizumab versus pembrolizumab in PD-L1-positive advanced non-small-cell lung cancer (OptiTROP-Lung05): interim analysis of a randomised, open-label, phase 3 trial.
In 413 PD-L1–positive, driver-negative advanced NSCLC patients, sacituzumab tirumotecan plus pembrolizumab significantly prolonged PFS versus pembrolizumab alone (median not reached vs 5.7 months; HR 0.35), with benefit across PD-L1 subgroups. Grade ≥3 adverse events were more frequent with combination (55% vs 31%).
Impact: This phase 3 interim analysis shows a large PFS advantage of ADC–IO combination over PD-1 monotherapy in first-line PD-L1–positive NSCLC, potentially redefining the standard of care.
Clinical Implications: For PD-L1–positive, driver-negative advanced NSCLC, ADC–IO combinations may supersede PD-1 monotherapy; clinicians should anticipate higher grade ≥3 toxicities and monitor accordingly while awaiting OS and quality-of-life data.
Key Findings
- Median PFS was significantly longer with sac-TMT plus pembrolizumab versus pembrolizumab alone (NR vs 5.7 months; HR 0.35, p<0.0001).
- Benefit was consistent across PD-L1 TPS 1–49% (HR 0.28) and ≥50% (HR 0.47) subgroups.
- Grade ≥3 treatment-emergent adverse events occurred in 55% (combo) vs 31% (pembro).
Methodological Strengths
- Randomised phase 3 design with blinded independent central review for PFS
- Large multicentre enrollment with prespecified subgroup analyses by PD-L1 expression
Limitations
- Open-label design may bias patient-reported or management-dependent endpoints
- Interim analysis with immature OS; single-country population may limit generalisability
Future Directions: Report OS, duration of response, and quality-of-life outcomes; evaluate biomarkers of response/resistance and optimal sequencing versus chemo-IO or TROP2 ADC monotherapies.
BACKGROUND: Sacituzumab tirumotecan (sac-TMT), a trophoblast cell-surface antigen 2-targeting antibody-drug conjugate, combined with programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitors, has shown promising antitumour activity as first-line therapy for non-small-cell lung cancer (NSCLC) in early-phase studies. Our aim was to evaluate the efficacy and safety of sac-TMT plus pembrolizumab as first-line treatment for patients with PD-L1-positive advanced NSCLC without targetable geno
2. Efficacy and safety of a 4-month quabodepistat, delamanid, and bedaquiline regimen for drug-susceptible pulmonary tuberculosis: a multicentre, open-label, randomised, proof-of-concept, non-inferiority, phase 2b/c trial.
Among 121 mITT participants, end-of-treatment sputum culture conversion was 96.0% for pooled DBQ 4‑month regimens versus 100% for standard 6‑month RHEZ, meeting non-inferiority (difference −4.0%, 80% CI −7.4 to 3.4). Adverse events were mostly mild–moderate; grade ≥3 events ranged 11–20% in DBQ arms with no treatment-related serious events.
Impact: Introduces a novel, all-oral, 4‑month regimen for drug-susceptible TB that could materially shorten therapy if validated in phase 3 with relapse-free cure endpoints.
Clinical Implications: If sustained cure is confirmed, DBQ could offer a shorter, fully oral option for drug-susceptible TB, improving adherence and programmatic feasibility; pharmacovigilance for cardiac and hepatic safety remains essential.
Key Findings
- Pooled DBQ 4‑month regimens achieved 96.0% end-of-treatment culture conversion vs 100% for 6‑month RHEZ; non-inferiority margin (12%) met (difference −4.0%, 80% CI −7.4 to 3.4).
- Adverse events were mostly mild–moderate; grade ≥3 events: 11–20% in DBQ arms vs 5% in RHEZ; no treatment-related serious AEs; one death unrelated to study drugs.
- Efficacy was consistent across DBQ dose levels (10, 30, 90 mg quabodepistat).
Methodological Strengths
- Prospective randomized, multicentre non-inferiority design with predefined 12% margin
- Dose-ranging evaluation across three quabodepistat doses alongside standard comparators
Limitations
- Open-label design; primary endpoint limited to end-of-treatment culture conversion without relapse-free follow-up
- Single-country setting with modest sample size may limit generalisability
Future Directions: Proceed to phase 3 trials powered for relapse-free cure and safety; assess resistance amplification risk, PK–PD interactions, and programmatic implementation in diverse settings.
BACKGROUND: Combined therapy with delamanid, bedaquiline, and quabodepistat (DBQ) showed potent early bactericidal activity and was well tolerated in a phase 2a, 14-day early bactericidal activity trial in participants with drug-susceptible pulmonary tuberculosis. This subsequent proof-of-concept trial evaluated the efficacy and safety of a 4-month, three-dose level regimen of DBQ in participants with drug-susceptible pulmonary tuberculosis compared with 6 months of the standard of care. METHODS: This open-la
3. Asthma exacerbation profile of benralizumab for severe eosinophilic asthma (the BenRex study): a multicentre, prospective cohort study.
Across 121 assessed exacerbations in 156 patients on benralizumab, airway eosinophils were suppressed (median blood eosinophils 0/µL) while neutrophilic signatures predominated: sputum neutrophilia (55% of sampled events), CRP rise, NETs markers increase. Viruses were detected in 56% (clinically relevant in 20.5%) and new bacterial acquisition (M. catarrhalis, H. influenzae, S. pneumoniae) was observed. High FeNO (≥50 ppb) associated with lower odds of bacterial detection.
Impact: Clarifies that benralizumab-era exacerbations are largely non-eosinophilic and infection-associated, guiding precision management beyond eosinophil-targeted strategies.
Clinical Implications: For benralizumab-treated patients with exacerbations, consider early evaluation for viral/bacterial infection and neutrophilic inflammation; biomarker patterns (CRP, NETs, FeNO) may inform antibiotic decisions and adjunctive strategies.
Key Findings
- Blood eosinophils were suppressed at exacerbation (median 0/µL), while sputum neutrophilia occurred in 55% of sampled events.
- Systemic inflammation increased (CRP median 3.0→9.0 mg/L) with rises in DNA–neutrophil elastase complexes and azurocidin‑1.
- Viruses detected in 56.4% (clinically relevant 20.5%); new acquisition of M. catarrhalis, H. influenzae, and S. pneumoniae observed; FeNO ≥50 ppb associated with lower odds of bacterial detection.
Methodological Strengths
- Prospective, multicentre design with standardized sampling at exacerbation before treatment initiation
- Comprehensive profiling: FeNO, spirometry, sputum cytology, virology, bacterial acquisition, and NETs markers
Limitations
- Observational design limits causal inference and therapeutic recommendations
- Sputum available in a subset; UK cohort predominantly White may limit generalisability
Future Directions: Interventional trials testing infection-targeted and neutrophil-modulating strategies during biologic-era exacerbations; validation of biomarker-guided algorithms.
BACKGROUND: Benralizumab, an interleukin-5 receptor α antagonist, depletes blood eosinophils, reducing exacerbations of severe asthma by approximately 50% versus placebo. In this study, we aimed to characterise mechanisms underlying exacerbations occurring on benralizumab. METHODS: BenRex, a multicentre, prospective cohort study, recruited participants meeting national licensing criteria for benralizumab for asthma. The study was conducted in 15 UK severe asthma centres. After collecting baseline data, open-