Weekly Respiratory Research Analysis
This week prioritized trials and mechanistic studies that shift prevention and treatment strategies for respiratory disease: two late‑phase randomized trials established new therapeutic options in advanced lung cancer (a TROP2‑targeted ADC improving survival after EGFR‑TKI resistance and a bispecific PD‑1/VEGF‑A antibody outperforming a PD‑1 comparator in squamous NSCLC), and a large pooled randomized analysis supported preferential use of high‑dose influenza vaccine in older adults to reduce ho
Summary
This week prioritized trials and mechanistic studies that shift prevention and treatment strategies for respiratory disease: two late‑phase randomized trials established new therapeutic options in advanced lung cancer (a TROP2‑targeted ADC improving survival after EGFR‑TKI resistance and a bispecific PD‑1/VEGF‑A antibody outperforming a PD‑1 comparator in squamous NSCLC), and a large pooled randomized analysis supported preferential use of high‑dose influenza vaccine in older adults to reduce hospitalizations. Together these papers accelerate clinical adoption of novel biologics and vaccine policy updates while highlighting translational mechanistic insights that may yield new adjunctive respiratory therapies.
Selected Articles
1. Sacituzumab Tirumotecan in EGFR-TKI-Resistant,
In a phase 3 randomized trial (n=376) of patients with EGFR‑TKI–resistant lung cancer, sacituzumab tirumotecan (a TROP2‑targeted antibody–drug conjugate) significantly improved progression‑free survival (8.3 vs 4.3 months; HR 0.49) and overall survival (HR 0.60; P=0.001) compared with chemotherapy, with manageable but frequent grade ≥3 toxicities (neutropenia predominating).
Impact: Demonstrates a survival advantage of a TROP2‑targeted ADC in a previously unmet setting (post‑EGFR‑TKI resistance), potentially establishing a new standard of care and guiding biomarker development for patient selection.
Clinical Implications: Consider prioritizing sacituzumab tirumotecan over conventional chemotherapy for patients with EGFR‑TKI–resistant disease where appropriate, with proactive monitoring and management of neutropenia and other grade ≥3 adverse events.
Key Findings
- Progression‑free survival improved to 8.3 vs 4.3 months (HR 0.49; 95% CI 0.39–0.62).
- Overall survival significantly longer with sacituzumab tirumotecan (HR 0.60; 95% CI 0.44–0.82; P=0.001); 18‑month OS 65.8% vs 48.0%.
- Grade ≥3 adverse events common (58.0%), neutropenia most frequent; serious adverse events lower than chemo (9.0% vs 17.6%).
2. Ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy as first-line treatment for advanced squamous non-small-cell lung cancer (HARMONi-6): a randomised, double-blind, phase 3 trial.
HARMONi‑6 (n=532) showed ivonescimab (a bispecific PD‑1/VEGF‑A antibody) plus chemotherapy significantly prolonged median PFS versus tislelizumab plus chemotherapy (11.1 vs 6.9 months; HR 0.60), with consistent benefit across PD‑L1 subgroups and a manageable safety profile (grade ≥3 events 64% vs 54%).
Impact: Provides head‑to‑head randomized evidence that a bispecific PD‑1/VEGF‑A strategy improves first‑line outcomes in squamous NSCLC, a subgroup with limited prior advances, potentially redefining first‑line immunotherapy choices.
Clinical Implications: Ivonescimab plus chemotherapy may be considered as a first‑line option regardless of PD‑L1 expression; clinicians should weigh PFS benefit against increased grade ≥3 toxicities and monitor for hemorrhagic and immune‑related events.
Key Findings
- Median PFS 11.1 vs 6.9 months favoring ivonescimab (HR 0.60; one‑sided p<0.0001).
- Benefit consistent across PD‑L1 subgroups.
- Grade ≥3 treatment‑related AEs: 64% (ivonescimab) vs 54% (tislelizumab); immune‑related grade ≥3 AEs similar (9% vs 10%).
3. Effectiveness of high-dose influenza vaccine against hospitalisations in older adults (FLUNITY-HD): an individual-level pooled analysis.
A prespecified individual‑level pooled analysis of two harmonized randomized pragmatic trials (n=466,320; ages ≥65) found high‑dose inactivated influenza vaccine reduced hospitalizations for influenza or pneumonia versus standard dose (relative VE 8.8%; 95% CI 1.7–15.5) and decreased lab‑confirmed influenza hospitalizations more markedly (rVE 31.9%). Mortality and serious adverse events were similar between groups.
Impact: Largest randomized pooled evidence supporting preferential use of high‑dose influenza vaccine in older adults to reduce severe respiratory hospitalizations, informing vaccine policy and procurement decisions.
Clinical Implications: Health systems and clinicians should favor high‑dose influenza vaccination for adults ≥65 where available to reduce hospitalizations for influenza/pneumonia and cardiorespiratory causes, while monitoring cost‑effectiveness and season‑specific performance.
Key Findings
- Influenza or pneumonia hospitalizations reduced: 0.56% (HD) vs 0.62% (SD); relative VE 8.8% (95% CI 1.7–15.5).
- Lab‑confirmed influenza hospitalizations reduced substantially (rVE 31.9%; 95% CI 19.7–42.2).
- All‑cause hospitalizations modestly reduced; mortality similar between groups.