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

Myung-Ju Ahn; Kentaro Tanaka; Luis Paz-Ares; Robin Cornelissen; Nicolas Girard; Elvire Pons-Tostivint; David Vicente Baz; Shunichi Sugawara; Manuel Cobo; Maurice Pérol; Céline Mascaux; Elena Poddubskaya; Satoru Kitazono; Hidetoshi Hayashi; Min Hee Hong; Enriqueta Felip; Richard Hall; Oscar Juan-Vidal; Daniel Brungs; Shun Lu; Marina Garassino; Michael Chargualaf; Yong Zhang; Paul Howarth; Deise Uema; Aaron Lisberg; Jacob Sands; TROPION-Lung01 Trial Investigators

doi:10.1200/jco-24-01544

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

Authors: Myung-Ju Ahn ; Kentaro Tanaka ; Luis Paz-Ares ; Robin Cornelissen ; Nicolas Girard ; Elvire Pons-Tostivint ; David Vicente Baz ; Shunichi Sugawara ; Manuel Cobo ; Maurice Pérol ; Céline Mascaux ; Elena Poddubskaya ; Satoru Kitazono ; Hidetoshi Hayashi ; Min Hee Hong ; Enriqueta Felip ; Richard Hall ; Oscar Juan-Vidal ; Daniel Brungs ; Shun Lu ; Marina Garassino ; Michael Chargualaf ; Yong Zhang ; Paul Howarth ; Deise Uema ; Aaron Lisberg ; Jacob Sands ; TROPION-Lung01 Trial Investigators

Citation: JOURNAL OF CLINICAL ONCOLOGY, Vol.43(3) : 260-272, 2025-01

Journal Title: JOURNAL OF CLINICAL ONCOLOGY

ISSN: 0732-183X

Issue Date: 2025-01

MeSH: Adult ; Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung* / drug therapy ; Carcinoma, Non-Small-Cell Lung* / mortality ; Carcinoma, Non-Small-Cell Lung* / pathology ; Docetaxel* / administration & dosage ; Docetaxel* / adverse effects ; Docetaxel* / therapeutic use ; Female ; Humans ; Immunoconjugates / adverse effects ; Immunoconjugates / therapeutic use ; Lung Neoplasms* / drug therapy ; Lung Neoplasms* / mortality ; Lung Neoplasms* / pathology ; Male ; Middle Aged ; Progression-Free Survival

Abstract: Purpose: 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).

Methods: Patients received Dato-DXd 6 mg/kg or docetaxel 75 mg/m2 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.

Results: 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]; P = .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]; P = .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.

Conclusion: 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.

Trial registration: ClinicalTrials.gov NCT04656652.