Weekly Respiratory Research Analysis
This week’s respiratory literature highlights three practice‑shifting therapeutic trials and implentation studies: a multicenter phase 3 trial showing the DLL3-directed T‑cell engager tarlatamab significantly improves overall survival in relapsed small‑cell lung cancer; a randomized non‑inferiority trial demonstrating a 16‑week clofazimine‑based regimen is comparable to standard 24‑week therapy for drug‑susceptible pulmonary tuberculosis; and randomized data showing an antibody–drug conjugate (s
Summary
This week’s respiratory literature highlights three practice‑shifting therapeutic trials and implentation studies: a multicenter phase 3 trial showing the DLL3-directed T‑cell engager tarlatamab significantly improves overall survival in relapsed small‑cell lung cancer; a randomized non‑inferiority trial demonstrating a 16‑week clofazimine‑based regimen is comparable to standard 24‑week therapy for drug‑susceptible pulmonary tuberculosis; and randomized data showing an antibody–drug conjugate (sacituzumab tirumotecan) improves response and survival versus docetaxel in previously treated NSCLC. Across the week, translation of diagnostics (targeted NGS, PET‑first algorithms) and host‑directed biologics/AI‑driven drug discovery emerged as priority trends with direct clinical implications.
Selected Articles
1. Tarlatamab in Small-Cell Lung Cancer after Platinum-Based Chemotherapy.
In a multinational phase 3 open‑label RCT (n=509) for patients with SCLC progressing during/after platinum therapy, tarlatamab significantly improved median overall survival versus physician‑choice chemotherapy (13.6 vs 8.3 months; HR 0.60, P<0.001), with lower rates of grade ≥3 adverse events and fewer discontinuations. PFS and patient‑reported respiratory symptoms also favored tarlatamab.
Impact: First phase 3 RCT demonstrating a DLL3‑directed T‑cell engager produces a clear survival benefit over chemotherapy in previously treated SCLC — a paradigm shift in a disease with few effective salvage options.
Clinical Implications: Tarlatamab should be considered a preferred second‑line option for relapsed SCLC after platinum therapy; clinicians must monitor for immune‑engager–related effects (e.g., CRS, neurologic events) while integrating into treatment sequencing.
Key Findings
- Median overall survival 13.6 months (tarlatamab) vs 8.3 months (chemotherapy); HR 0.60, P<0.001.
- Lower incidence of grade ≥3 adverse events (54% vs 80%) and fewer treatment discontinuations (5% vs 12%) with tarlatamab.
- Progression‑free survival and patient‑reported dyspnea/cough improved with tarlatamab.
2. Four-month clofazimine regimen for susceptible pulmonary TB: a randomized clinical trial.
CORTAIL, a multicenter randomized non‑inferiority trial (n=322), compared a 16‑week clofazimine‑based regimen with the standard 24‑week regimen for drug‑susceptible pulmonary TB. Relapse at 3 months post‑treatment and 1‑year relapse rates, sputum conversion, and bacteriologic cure were comparable between arms, and safety was acceptable, supporting feasibility of shortening therapy.
Impact: High‑quality RCT evidence that safely shortens drug‑susceptible TB treatment from 6 months to 4 months would have major public‑health and implementation implications (adherence, toxicity, costs) if replicated and adopted.
Clinical Implications: If validated in broader settings, a 4‑month clofazimine‑containing regimen could be adopted as a new standard for drug‑susceptible pulmonary TB, particularly in programs struggling with adherence to longer courses; monitoring for clofazimine toxicities and resistance surveillance is required.
Key Findings
- Non‑inferiority for relapse at 3 months post‑treatment: 3.2% (short) vs 1.9% (standard) within predefined margin.
- No significant difference in 1‑year relapse, sputum conversion, or bacteriologic cure between arms.
- Safety profile acceptable across 11 centers; trial registered (CTRI/2019/03/018102).
3. Sacituzumab tirumotecan versus docetaxel for previously treated
In a multicenter randomized (2:1) trial (n=137) of previously treated advanced NSCLC, sacituzumab tirumotecan achieved a higher blinded objective response rate (45%) and improved progression‑free and overall survival versus docetaxel, with a manageable safety profile, supporting ADC use over chemotherapy in this setting.
Impact: Randomized head‑to‑head evidence that an ADC outperforms docetaxel on ORR, PFS and OS in previously treated NSCLC supports changing second‑line standards and expands ADC utility in thoracic oncology.
Clinical Implications: Consider sacituzumab tirumotecan over docetaxel after platinum failure in appropriate patients, with attention to ADC‑specific toxicities and access considerations.
Key Findings
- Blinded ORR 45% with sacituzumab tirumotecan vs lower ORR with docetaxel; PFS and OS improved at median 12.2 months follow‑up.
- Safety profile manageable supporting clinical adoption pending wider validation.