Daily Respiratory Research Analysis
Three impactful respiratory studies stood out today: a large prospective study shows that elexacaftor-tezacaftor-ivacaftor can partially reverse bronchial dilatations in adolescents with cystic fibrosis; a double-blind RCT (COMPEL) demonstrates that continuing osimertinib with platinum chemotherapy improves PFS after first-line osimertinib progression in EGFR-mutated NSCLC; and near real-time surveillance in the Vaccine Safety Datalink supports the safety of RSV vaccines in older adults.
Summary
Three impactful respiratory studies stood out today: a large prospective study shows that elexacaftor-tezacaftor-ivacaftor can partially reverse bronchial dilatations in adolescents with cystic fibrosis; a double-blind RCT (COMPEL) demonstrates that continuing osimertinib with platinum chemotherapy improves PFS after first-line osimertinib progression in EGFR-mutated NSCLC; and near real-time surveillance in the Vaccine Safety Datalink supports the safety of RSV vaccines in older adults.
Research Themes
- Disease-modifying therapy and structural lung change in cystic fibrosis
- Post-progression treatment strategy in EGFR-mutated NSCLC
- Real-world vaccine safety surveillance for RSV vaccines in older adults
Selected Articles
1. Effect of elexacaftor-tezacaftor-ivacaftor on bronchial dilatations in adolescents with cystic fibrosis: a multicentre prospective observational study.
In a 12-month multicentre prospective cohort of 320 adolescents with cystic fibrosis, ETI therapy was associated with radiologic reversal of bronchial dilatations on chest CT, alongside improvements in lung function and biomarkers (e.g., sweat chloride) with correlations to reduced airway inflammation.
Impact: This study provides rare evidence that structural airway damage in cystic fibrosis can be partially reversible under CFTR modulator therapy, reframing disease-modifying expectations in adolescence.
Clinical Implications: ETI may not only stabilize but reverse airway structural damage in adolescents with cystic fibrosis, supporting early initiation and sustained therapy. Imaging and inflammation metrics could be integrated into longitudinal monitoring.
Key Findings
- Bronchial dilatations showed radiologic reversal over 12 months of ETI therapy in adolescents.
- Functional and biomarker improvements accompanied structural changes (e.g., improved lung function and reduced sweat chloride).
- Structural improvements correlated with reduced airway inflammation.
- Benefits were observed across both CFTR modulator–naïve patients and those switched from lumacaftor–ivacaftor.
Methodological Strengths
- Prospective, multicentre cohort across 33 pediatric CF centers with 12-month follow-up.
- Primary structural endpoint using standardized chest CT, complemented by functional and inflammatory measures.
Limitations
- Observational design without a randomized control group.
- Adolescent-only cohort with 12-month horizon may limit generalizability and long-term inference.
Future Directions: Randomized or controlled imaging substudies to confirm reversibility, mechanistic work linking CFTR restoration to airway remodeling, and evaluation of timing/age windows for maximal structural benefit.
2. COMPEL: osimertinib plus platinum-based chemotherapy in patients with EGFR-mutated advanced NSCLC and progression on first-line osimertinib.
In the double-blind COMPEL RCT (n=98), continuing osimertinib with platinum-based chemotherapy after non-CNS progression on first-line osimertinib halved the risk of progression (median PFS 8.4 vs 4.4 months; HR 0.43), with a non-significant OS advantage and higher grade ≥3 toxicity.
Impact: Provides randomized evidence to support continuing EGFR-TKI with chemotherapy beyond progression, a common yet debated strategy in EGFR-mutated NSCLC.
Clinical Implications: For EGFR-mutated advanced NSCLC with non-CNS progression on first-line osimertinib, maintaining osimertinib with platinum doublet can be considered to extend PFS, with counseling on increased toxicity and uncertain OS benefit.
Key Findings
- Median PFS improved from 4.4 to 8.4 months (HR 0.43, 95% CI 0.27–0.70) with osimertinib plus chemotherapy.
- Median OS numerically longer (15.9 vs 9.8 months; HR 0.71, 95% CI 0.42–1.23) but not statistically significant.
- CNS PFS favored the combination in patients without baseline CNS metastases (HR 0.56, 95% CI 0.27–1.13).
- Grade ≥3 adverse events were more frequent with the combination (63% vs 46%).
Methodological Strengths
- Randomized, double-blind design with registered protocol (NCT04765059).
- Pre-specified CNS-related outcomes and robust PFS effect size.
Limitations
- Small sample size (n=98) limits power for OS and subgroup analyses.
- Increased grade ≥3 toxicity and absence of predictive biomarker stratification.
Future Directions: Larger phase III trials with biomarker-driven stratification and patient-reported outcomes to clarify OS, CNS control, and tolerability of TKI continuation beyond progression.
3. Near real-time surveillance and tree-based data mining to assess the safety of respiratory syncytial virus vaccines in older adults in the vaccine safety datalink.
Using rapid cycle analysis (n=436,823) and self-controlled tree-based data mining (n=248,056), post-licensure surveillance found no confirmed safety signals for RSV vaccines in adults ≥60 years; an initial ITP signal for Arexvy was not supported after medical record confirmation.
Impact: Delivers high-quality, near real-time population safety data supporting RSV vaccine deployment in older adults, addressing a key evidence gap shortly after licensure.
Clinical Implications: Clinicians can counsel older adults that current surveillance shows no confirmed increased risk for evaluated AESIs after RSV vaccination, supporting uptake while continuing vigilance for rare events.
Key Findings
- Rapid cycle analysis of 436,823 vaccinees showed no statistical signal for 11 of 12 prespecified adverse events.
- An initial signal for immune thrombocytopenic purpura following Arexvy was not confirmed after medical record review and re-analysis.
- Self-controlled tree-based data mining (248,056 vaccinees) identified no significant clusters of ICD-10 diagnoses 1–56 days post-vaccination.
Methodological Strengths
- Near real-time rapid cycle analysis with sequential monitoring across multiple sites.
- Complementary, hypothesis-free self-controlled tree-based data mining and outcome confirmation via medical record review.
Limitations
- Limited power to detect very rare adverse events and short risk windows post-vaccination.
- Observational design susceptible to misclassification and residual confounding despite robust methods.
Future Directions: Extended surveillance across subsequent seasons, linkage with additional data sources, and targeted studies for rare outcomes (e.g., Guillain–Barré syndrome) to refine risk estimates.