Background
Phase 3 RCT (TROPION-Lung01); N=604 advanced/metastatic NSCLC previously treated, comparing the TROP2 ADC datopotamab deruxtecan vs docetaxel.
Interventions and follow up
Arm A: Datopotamab deruxtecan (Dato-DXd) 6 mg/kg IV q3w
Arm B: Docetaxel 75 mg/m² IV q3w
Primary endpoint: PFS and OS
mFollow up: 23.1mo
Arm B: Docetaxel 75 mg/m² IV q3w
Primary endpoint: PFS and OS
mFollow up: 23.1mo
Results
mPFS (ITT): 4.4mo vs 3.7mo, HR 0.75, 95%CI 0.62-0.92, P<.001
mPFS (non-squamous): 5.5mo vs 3.6mo, HR 0.63, 95%CI 0.51-0.79, P<.001
mOS (ITT): 12.9mo vs 11.8mo, HR 0.94, 95%CI 0.78-1.14, P=.53
mOS (non-squamous): 14.6mo vs 12.3mo, HR 0.84, 95%CI 0.68-1.05, P=.12
mOS (squamous): 7.6mo vs 9.4mo, HR 1.32, 95%CI 0.91-1.92
TROP2 QCS-NMR positive ORR: 32.7% vs 10.3%; mPFS 6.9mo vs 4.1mo, HR 0.57, 95%CI 0.41-0.79
TROP2 QCS-NMR negative ORR: 16.9% vs 15.1%; mPFS 2.9mo vs 4.0mo, HR 1.16, 95%CI 0.79-1.70
mPFS (non-squamous): 5.5mo vs 3.6mo, HR 0.63, 95%CI 0.51-0.79, P<.001
mOS (ITT): 12.9mo vs 11.8mo, HR 0.94, 95%CI 0.78-1.14, P=.53
mOS (non-squamous): 14.6mo vs 12.3mo, HR 0.84, 95%CI 0.68-1.05, P=.12
mOS (squamous): 7.6mo vs 9.4mo, HR 1.32, 95%CI 0.91-1.92
TROP2 QCS-NMR positive ORR: 32.7% vs 10.3%; mPFS 6.9mo vs 4.1mo, HR 0.57, 95%CI 0.41-0.79
TROP2 QCS-NMR negative ORR: 16.9% vs 15.1%; mPFS 2.9mo vs 4.0mo, HR 1.16, 95%CI 0.79-1.70
Adverse events
Mucosal: stomatitis 41% vs 2%
Hematologic: neutropenia 6% vs 23%; anemia 11% vs 9%
Pulmonary: interstitial lung disease/pneumonitis monitoring required (ADC class effect)
Hematologic: neutropenia 6% vs 23%; anemia 11% vs 9%
Pulmonary: interstitial lung disease/pneumonitis monitoring required (ADC class effect)
Conclusions
Dato-DXd modestly improved PFS over docetaxel (driven by non-squamous histology) without an OS benefit; squamous patients did worse. A TROP2 QCS-NMR biomarker enriched for benefit.
Key Limitations
No OS gain; harm signal in squamous histology; ILD risk; QCS-NMR biomarker exploratory and not yet validated/standardized.
Clinical Context
Negative for the OS co-primary endpoint; informed FDA review of Dato-DXd in non-squamous NSCLC and ongoing 1L trials (AVANZAR NCT05687266, TROPION-Lung10 NCT06357533). Not a guideline standard in 2L.