Author(s): Myung-Ju Ahn, MD, PhD1; Kentaro Tanaka, MD, PhD2; Luis Paz-Ares, MD, PhD3; Robin Cornelissen, MD, PhD4; Nicolas Girard, MD, PhD5; Elvire Pons-Tostivint, MD, PhD6; David Vicente Baz, MD7; Shunichi Sugawara, MD, PhD8; Manuel Cobo, MD, PhD9; Maurice Pérol, MD10; Céline Mascaux, MD, PhD11; Elena Poddubskaya, MD12; Satoru Kitazono, MD, PhD13; Hidetoshi Hayashi, MD, PhD14; Min Hee Hong, MD15; Enriqueta Felip, MD16; Richard Hall, MD17; Oscar Juan-Vidal, MD, PhD18; Daniel Brungs, MBBS19; Shun Lu, MD, PhD20; Marina Garassino, MD21; Michael Chargualaf, PharmD22; Yong Zhang, MSc22; Paul Howarth, MD22; Deise Uema, MD22; Aaron Lisberg, MD23; Jacob Sands, MD24
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.
Author Affiliations
1Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
2Kyushu University Hospital, Fukuoka, Japan
3Hospital Universitario 12 de Octubre, Madrid, Spain
4Erasmus MC Cancer Institute, Rotterdam, the Netherlands
5Institut Curie, Paris, France
6University Hospital of Nantes, Nantes, France
7Hospital Universitario Virgen Macarena, Seville, Spain
8Sendai Kousei Hospital, Sendai, Japan
9Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria University Hospitals, IBIMA, Málaga, Spain
10Centre Léon Bérard, Lyon, France
11Hopitaux Universitaire de Strasbourg, Strasbourg, France
12VitaMed LLC, Moscow, Russia
13The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
14Kindai University Hospital, Osaka, Japan
15Yonsei Cancer Center, Severance Hospital, Seoul, Republic of Korea
16Vall d’Hebron Hospital Campus, Vall d’Hebron Institute of Oncology, Universitat Autònoma de Barcelona, Spain
17University of Virginia Health System, Charlottesville, VA
18Hospital Universitari i Politecnic La Fe, Valencia, Spain
19Southern Medical Day Care Centre, University of Wollongong, Wollongong, Australia
20Shanghai Lung Cancer Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
21Department of Medicine, Hematology-Oncology Section, Thoracic Oncology Program, The University of Chicago Medicine & Biological Sciences, Chicago, IL
22Daiichi Sankyo, Basking Ridge, NJ
23Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA
24Dana-Farber Cancer Institute, Boston, MA
