Datopotamab Deruxtecan Versus Docetaxel for Previously Treated Advanced or Metastatic Non-Small Cell Lung Cancer: The Randomized, Open-Label Phase III TROPION-Lung01 Study

• Published in: Journal of clinical oncology p. JCO2401544
• Main Authors: Ahn, Myung-Ju, Tanaka, Kentaro, Paz-Ares, Luis, Cornelissen, Robin, Girard, Nicolas, Pons-Tostivint, Elvire, Vicente Baz, David, Sugawara, Shunichi, Cobo, Manuel, Pérol, Maurice, Mascaux, Céline, Poddubskaya, Elena, Kitazono, Satoru, Hayashi, Hidetoshi, Hong, Min Hee, Felip, Enriqueta, Hall, Richard, Juan-Vidal, Oscar, Brungs, Daniel, Lu, Shun, Garassino, Marina, Chargualaf, Michael, Zhang, Yong, Howarth, Paul, Uema, Deise, Lisberg, Aaron, Sands, Jacob
• Format: Journal Article
• Language: English
• Published: United States 09.09.2024
• ISSN: 0732-183X; 1527-7755; 1527-7755
• DOI: 10.1200/JCO-24-01544

The randomized, open-label, global phase III TROPION-Lung01 study compared the efficacy and safety of datopotamab deruxtecan (Dato-DXd) versus docetaxel in patients with pretreated advanced/metastatic non-small cell lung cancer (NSCLC). Patients received Dato-DXd 6 mg/kg or docetaxel 75 mg/m once every 3 weeks. Dual primary end points were progression-free survival (PFS) and overall survival (OS). Objective response rate, duration of response, and safety were secondary end points. In total, 299 and 305 patients were randomly assigned to receive Dato-DXd or docetaxel, respectively. The median PFS was 4.4 months (95% CI, 4.2 to 5.6) with Dato-DXd and 3.7 months (95% CI, 2.9 to 4.2) with docetaxel (hazard ratio [HR], 0.75 [95% CI, 0.62 to 0.91]; = .004). The median OS was 12.9 months (95% CI, 11.0 to 13.9) and 11.8 months (95% CI, 10.1 to 12.8), respectively (HR, 0.94 [95% CI, 0.78 to 1.14]; = .530). In the prespecified nonsquamous histology subgroup, the median PFS was 5.5 versus 3.6 months (HR, 0.63 [95% CI, 0.51 to 0.79]) and the median OS was 14.6 versus 12.3 months (HR, 0.84 [95% CI, 0.68 to 1.05]). In the squamous histology subgroup, the median PFS was 2.8 versus 3.9 months (HR, 1.41 [95% CI, 0.95 to 2.08]) and the median OS was 7.6 versus 9.4 months (HR, 1.32 [95% CI, 0.91 to 1.92]). Grade ≥3 treatment-related adverse events occurred in 25.6% and 42.1% of patients, and any-grade adjudicated drug-related interstitial lung disease/pneumonitis occurred in 8.8% and 4.1% of patients, in the Dato-DXd and docetaxel groups, respectively. Dato-DXd significantly improved PFS versus docetaxel in patients with advanced/metastatic NSCLC, driven by patients with nonsquamous histology. OS showed a numerical benefit but did not reach statistical significance. No unexpected safety signals were observed.