Daily Respiratory Research Analysis
A phase 3 randomized trial showed rezivertinib nearly doubled progression-free survival versus gefitinib in first-line EGFR-mutated NSCLC. Nationwide real-world data from Spain demonstrated strong effectiveness of nirsevimab in preventing infant RSV hospitalizations and critical care needs, while a large U.S. ED cohort found adult RSV test positivity was not linked to higher hospitalization or 30-day mortality. Together, these studies refine oncology practice and respiratory virus prevention and
Summary
A phase 3 randomized trial showed rezivertinib nearly doubled progression-free survival versus gefitinib in first-line EGFR-mutated NSCLC. Nationwide real-world data from Spain demonstrated strong effectiveness of nirsevimab in preventing infant RSV hospitalizations and critical care needs, while a large U.S. ED cohort found adult RSV test positivity was not linked to higher hospitalization or 30-day mortality. Together, these studies refine oncology practice and respiratory virus prevention and triage.
Research Themes
- Targeted therapy advancements in EGFR-mutated NSCLC
- Population-level RSV immunoprophylaxis effectiveness in infants
- Risk stratification for adult RSV-positive acute respiratory illness
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 369 EGFR-mutated NSCLC patients, rezivertinib nearly doubled median progression-free survival versus gefitinib (19.3 vs 9.6 months; HR 0.48) with similar rates of grade ≥3 treatment-related adverse events. One treatment-related death (pneumonia/interstitial lung disease) occurred with rezivertinib.
Impact: This high-quality phase 3 RCT provides compelling first-line evidence for a next-generation EGFR TKI that significantly prolongs PFS compared with gefitinib. It is likely to influence treatment algorithms in EGFR-mutated NSCLC.
Clinical Implications: Rezivertinib is a strong first-line option for EGFR exon19del/L858R NSCLC. Clinicians should weigh PFS benefit against potential ILD risk, monitor closely, and await OS/CNS outcomes and comparative data versus osimertinib.
Key Findings
- Median PFS 19.3 months with rezivertinib vs 9.6 months with gefitinib (HR 0.48, p<0.0001).
- Grade ≥3 treatment-emergent and treatment-related adverse events were similar between arms (23% TRAEs in each arm).
- One treatment-related death (pneumonia/interstitial lung disease) occurred in the rezivertinib arm.
Methodological Strengths
- Multicentre, double-blind, randomized phase 3 design with masked independent central review of PFS.
- Adequate sample size with prespecified subgroup analyses and balanced arms.
Limitations
- Population entirely in China; generalizability outside East Asia uncertain.
- Overall survival and CNS efficacy not yet mature; no head-to-head comparison with osimertinib.
Future Directions: Head-to-head comparisons with third-generation TKIs (e.g., osimertinib), evaluation of CNS control, resistance mechanisms, and sequencing strategies; broader multiethnic confirmatory trials.
BACKGROUND: This study aimed to compare the efficacy and safety of rezivertinib (BPI-7711) and gefitinib as first-line therapies in patients with EGFR-mutated locally advanced or metastatic non-small-cell lung cancer (NSCLC). METHODS: This multicentre, double-blind, randomised, phase 3 study (REZOR) included eligible patients from 50 hospitals across China. Those who had been histologically or cytologically confirmed as having NSCLC with EGFR exon 19 deletion or exon 21 Leu858Arg mutation by central laboratory were randomly assigned (1:1) to receive once daily either rezivertinib 180 mg or gefitinib 250 mg, until unacceptable toxicity occurred, disease progression, or other treatment discontinuation criteria were met. Each cycle lasted for 21 days. The primary endpoint was progression-free survival evaluated by masked independent central review (MICR) in the intention-to-treat set. This trial is registered with ClinicalTrials.gov, NCT03866499 and follow-up is ongoing. FINDINGS: Between July 15, 2019, and Feb 14, 2022, 695 patients were screened. Among them, 369 eligible patients were randomly assigned to receive either rezivertinib 180 mg/day plus placebo (n=184) or gefitinib 250 mg/day plus placebo (n=185) in a 1:1 ratio; all of eligible participants were included in the intention-to-treat set. Median MICR-assessed progression-free survival was 19·3 months (95% CI 13·8-22·1) in the rezivertinib group and 9·6 months (8·4-11·3) in the gefitinib group (hazard ratio [HR)
2. Effectiveness of catch-up and at-birth nirsevimab immunisation against RSV hospital admission in the first year of life: a population-based case-control study, Spain, 2023/24 season.
Nationwide matched case-control analyses showed nirsevimab reduced RSV hospitalizations by 71–80% (catch-up) and 78–83% (at-birth), with similar protection against ICU admission and mechanical ventilation. Effectiveness was modestly lower in preterm and low-birthweight infants but remained substantial.
Impact: This provides robust real-world effectiveness for universal infant RSV immunoprophylaxis, supporting rapid policy implementation and resource allocation during the RSV season.
Clinical Implications: Health systems can expect substantial reductions in RSV hospitalizations and critical care demand with broad nirsevimab coverage. Prioritize outreach to preterm/low-birthweight infants given slightly reduced effectiveness.
Key Findings
- Catch-up nirsevimab effectiveness: ITT 71% (95% CI 65–76), PP 80% (95% CI 75–84).
- At-birth nirsevimab effectiveness: ITT 78% (95% CI 73–82), PP 83% (95% CI 79–87).
- Protection extended to ICU admission and mechanical ventilation; effectiveness slightly lower (≈60–70%) in preterm/low-birthweight infants.
Methodological Strengths
- Nationwide, population-based matched case-control design with four matched controls per case.
- Causal ITT and PP estimates using inverse-probability-of-immunisation weighted conditional logistic regression.
Limitations
- Observational design susceptible to residual confounding and misclassification.
- Evaluation limited to a single RSV season; durability and inter-season variability not assessed.
Future Directions: Assess multi-season durability, cost-effectiveness, and implementation strategies; evaluate effectiveness in high-risk subgroups and interaction with maternal RSV vaccination programs.
BackgroundRespiratory syncytial virus (RSV) causes substantial morbidity in infants < 1 year. In October 2023, Spain recommended the monoclonal antibody nirsevimab to all children born since 1 April 2023, at birth or as catch-up if born before October 2023.AimWe estimated nirsevimab effectiveness in preventing RSV hospitalisations during the 2023/24 season.MethodsWe conducted a nationwide population-based matched case-control study. Cases were children hospitalised for lower respiratory tract infection who were RSV PCR-positive. For each case, we selected four population density controls born in the same province and date (±2 days). We defined at-birth immunisation as receiving nirsevimab during the first 2 weeks of life, and catch-up immunisation within 30 days from campaign onset. Causal intention-to-treat (ITT) and per-protocol (PP) effectiveness was estimated using inverse-probability-of-immunisation weighted conditional logistic regression.ResultsWe included 406 cases and 1,623 controls in catch-up and 546 cases and 2,182 controls in at-birth immunisation studies. Effectiveness in preventing RSV hospitalisations for catch-up immunisation was 71% (95% confidence interval (CI): 65-76) by ITT and 80% (95% CI: 75-84) PP. Effectiveness for at-birth immunisation was 78% (95% CI: 73-82) by ITT and 83% (95% CI: 79-87) PP. Effectiveness was similar for ICU admission, need of mechanical ventilation, and RSV viral subgroups A and B. Children born pre-term or with birthweight < 2,500 g showed lower PP effectiveness of 60-70%.ConclusionsPopulation-level nirsevimab immunoprophylaxis in children in their first RSV season was very effective in preventing RSV hospitalisations, ICU admission and mechanical ventilation, with reduced but still high effectiveness for pre-term and low-birthweight children.
3. Laboratory Confirmation of Respiratory Syncytial Virus Infection Is Not Associated With an Increased Risk of Death in Adults With Acute Respiratory Illness.
In over 1.2 million ED ARI encounters across 91 hospitals, RSV positivity (2.4%) was not associated with higher hospitalization or 30-day mortality after adjustment (aOR 0.79 and 0.62, respectively). Age ≥65, worse vital signs, male sex, and heart failure—not RSV positivity—drove mortality risk.
Impact: This large prospective network study informs ED triage and resource use by showing RSV test positivity alone does not signal worse short-term outcomes in adults with ARI.
Clinical Implications: Adult ED triage should prioritize age, clinical status, and comorbidities over RSV status; indiscriminate RSV testing may have limited prognostic value for short-term outcomes.
Key Findings
- Among 1,210,394 ARI adult ED encounters, 28.5% were tested for RSV and 2.4% were positive.
- Adjusted analyses showed RSV+ status was not associated with higher hospitalization (aOR 0.79) or 30-day mortality (aOR 0.62) vs RSV-.
- Age ≥65, worsening vital signs, male sex, and heart failure were independently associated with death.
Methodological Strengths
- Prospective multicenter surveillance across 91 hospitals with very large sample size.
- Use of generalized estimating equations to adjust for clustering and confounders.
Limitations
- RSV test ordering was not standardized and may reflect clinician selection biases.
- Limited to short-term outcomes; viral load and timing of illness onset not detailed.
Future Directions: Define which adult subgroups (e.g., severe immunosuppression) may benefit from RSV-specific testing; integrate clinical prediction tools for ED triage.
BACKGROUND: Limited data have described the testing patterns and outcomes of adults (≥18 years) with acute respiratory illness (ARI) in the emergency department setting. METHODS: This prospective cohort study includes patients with ARI from a program sponsored by the Centers for Disease Control and Prevention entitled Respiratory Virus Laboratory Emergency Department Network Surveillance (RESP-LENS) from August 2021 until March 2024 (91 hospitals). Patients with ARIs were identified weekly by electronic surveillance for 1 or more of 130 RESULTS: From 1 210 394 patients with ARI, 345 185 (28.5%) adults underwent RSV testing, which was positive in 2.4%. In adults who were RSV+, the overall mortality rate was 1.9% as compared with 2.9% in adults who were RSV-. Mortality with RSV+ status increased with age ≥65 years to 3.8% (95% CI, 3.1%-4.5%). However, in the generalized estimating equation, RSV+ status was not associated with a higher rate of hospitalization (adjusted odds, 0.79; 95% CI, .75-.84) or 30-day mortality (odds, 0.62; 95% CI, .53-.74) relative to those who were RSV-. Age ≥65 years, incremental worsening of vital signs, male sex, and heart failure were independently associated with death. CONCLUSIONS: Among adults with ARI presenting to an emergency department who were tested for RSV as part of their usual care, laboratory-confirmed RSV positivity was not associated with increased risk, including hospitalization, intensive care unit requirement, or death.