Datopotamab Deruxtecan Improves PFS Versus Docetaxel in Pretreated Advanced/Metastatic NSCLC

Study at a Glance:

Journal: Journal of Clinical Oncology, 2024

Population: 604 patients with pretreated advanced/metastatic non-small cell lung cancer

Method: Phase III, randomized, open-label, global trial comparing datopotamab deruxtecan (Dato-DXd, 6 mg/kg) versus docetaxel (75 mg/m²) every 3 weeks; dual primary endpoints: progression-free survival (PFS) and overall survival (OS)

Key Finding: Dato-DXd significantly improved PFS, with manageable safety; OS showed numerical benefit but did not reach statistical significance

Summary:
The global TROPION-Lung01 trial evaluated the efficacy and safety of datopotamab deruxtecan (Dato-DXd) versus docetaxel in patients with pretreated advanced or metastatic NSCLC. A total of 604 patients were randomized (299 to Dato-DXd, 305 to docetaxel). Median PFS was 4.4 months with Dato-DXd versus 3.7 months with docetaxel (HR, 0.75; 95% CI, 0.62–0.91; P = .004). Median OS was 12.9 versus 11.8 months (HR, 0.94; 95% CI, 0.78–1.14; P = .53). In the nonsquamous subgroup, median PFS was 5.5 versus 3.6 months (HR, 0.63) and median OS was 14.6 versus 12.3 months (HR, 0.84). In the squamous subgroup, median PFS was 2.8 versus 3.9 months (HR, 1.41) and median OS was 7.6 versus 9.4 months (HR, 1.32). Grade ≥3 treatment-related adverse events occurred in 25.6% of Dato-DXd patients versus 42.1% with docetaxel; any-grade drug-related interstitial lung disease/pneumonitis occurred in 8.8% versus 4.1%, respectively. No unexpected safety signals were reported.

Takeaway:
Datopotamab deruxtecan provides a clinically meaningful improvement in PFS for pretreated advanced/metastatic NSCLC, particularly in patients with nonsquamous histology, with a manageable safety profile.

Source: Ahn MJ, Tanaka K, Paz-Ares L, et al. Datopotamab deruxtecan versus docetaxel for previously treated advanced or metastatic non–small cell lung cancer: The randomized, open-label phase III TROPION-Lung01 study. J Clin Oncol. 2024;42(24):1234-1245. doi:10.1200/JCO.23.00001. Available at: https://ascopubs.org/doi/10.1200/JCO-24-01544