Weekly Respiratory Research Analysis
This week’s respiratory literature highlights rapid advances across prevention, therapeutics, and diagnostics. A multicentre phase 3 trial showed rezivertinib substantially prolongs PFS versus gefitinib in first-line EGFR‑mutated NSCLC. Biologic therapy (dupilumab) improved patient-reported outcomes in COPD with type 2 inflammation, and national observational data confirm strong maternal COVID‑19 vaccine effectiveness with meaningful infant protection. Together these studies are shifting treatme
Summary
This week’s respiratory literature highlights rapid advances across prevention, therapeutics, and diagnostics. A multicentre phase 3 trial showed rezivertinib substantially prolongs PFS versus gefitinib in first-line EGFR‑mutated NSCLC. Biologic therapy (dupilumab) improved patient-reported outcomes in COPD with type 2 inflammation, and national observational data confirm strong maternal COVID‑19 vaccine effectiveness with meaningful infant protection. Together these studies are shifting treatment options for selected phenotypes and reinforcing vaccination and genomic surveillance strategies.
Selected Articles
1. Rezivertinib versus gefitinib as first-line therapy for patients with EGFR-mutated locally advanced or metastatic non-small-cell lung cancer (REZOR): a multicentre, double-blind, randomised, phase 3 study.
In a multicentre double-blind phase 3 trial (n=369), rezivertinib nearly doubled median progression-free survival compared with gefitinib (19.3 vs 9.6 months; HR 0.48) with broadly similar rates of grade ≥3 adverse events. CNS and overall survival data remain immature; one treatment-related death (pneumonia/ILD) occurred in the rezivertinib arm.
Impact: Provides high‑quality randomized evidence that a next‑generation EGFR TKI substantially improves first‑line PFS in common sensitizing EGFR mutations, likely to influence treatment guidelines and sequencing decisions.
Clinical Implications: Rezivertinib should be considered a strong first‑line option for patients with exon 19 deletion or L858R EGFR mutations; clinicians must monitor for ILD and await comparative OS/CNS data versus third‑generation TKIs before definitive sequencing changes.
Key Findings
- Median MICR-assessed PFS: 19.3 months (rezivertinib) vs 9.6 months (gefitinib); HR 0.48.
- Grade ≥3 treatment-related adverse events were similar between arms (~23%).
- One treatment-related death (pneumonia/ILD) reported in the rezivertinib arm; OS and CNS outcomes pending.
2. Effect of Dupilumab on Health-Related Quality of Life and Respiratory Symptoms in Patients With COPD and Type 2 Inflammation: BOREAS and NOTUS.
Pooled analysis of two phase 3 RCTs (≈1,874 randomized; 1,660 completed 52 weeks) showed dupilumab added to standard triple therapy modestly but significantly improved SGRQ total (−3.4) and E‑RS:COPD total (−0.9) at 52 weeks, with consistent domain benefits for symptoms, activity, and breathlessness.
Impact: Demonstrates patient-centered benefits (symptoms, activity, quality of life) for a biologic in a COPD subgroup defined by type 2 inflammation, supporting phenotype-directed biologic use beyond asthma.
Clinical Implications: Consider dupilumab for COPD patients with evidence of type 2 inflammation not adequately controlled on inhaled triple therapy; incorporate shared decision‑making regarding symptom and QOL gains alongside exacerbation data.
Key Findings
- SGRQ total least-squares mean difference −3.4 vs placebo at 52 weeks (P < .0001).
- E‑RS:COPD total improved −0.9 vs placebo at 52 weeks (P = .0006), with breathlessness domain −0.6.
- Findings consistent across SGRQ domains (symptoms, activity, impacts) in 1,660 patients completing follow-up.
3. Vaccine effectiveness against mild and severe covid-19 in pregnant individuals and their infants in England: test negative case-control study.
A large national test-negative study in England found high vaccine effectiveness in pregnant individuals against symptomatic disease and hospitalisation for Delta and Omicron, with booster doses sustaining protection up to 15 weeks. Maternal vaccination in the third trimester conferred substantial infant protection up to 6 months (e.g., infant hospitalisation reduction >78% for Delta).
Impact: Provides policy‑relevant, population-level evidence supporting maternal primary and booster vaccination to protect both mothers and infants — highly actionable for prenatal vaccination programs.
Clinical Implications: Prioritise primary and booster COVID‑19 vaccination during pregnancy—especially late pregnancy—to reduce maternal disease and provide passive infant protection through the first six months of life.
Key Findings
- Booster effectiveness against symptomatic disease in pregnant individuals: 98.4% (delta) and 80.1% (omicron) peak estimates.
- Two-dose primary series effectiveness against delta hospital admission in pregnancy: 92.7%.
- Maternal vaccination in third trimester protected infants up to 6 months (e.g., hospital admission reduction 94.7% for delta).