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, M. Pérol, Céline Mascaux, Elena Poddubskaya, Satoru Kitazono, Hidetoshi Hayashi, Min Hee Hong, Enriqueta Felip, Richard D. Hall, Óscar Juan, Daniel Brungs, Shun Lü, Marina Chiara Garassino, Michael Chargualaf, Yong Zhang, Paul Howarth, Deise Uema, Aaron Lisberg, Jacob Sands, for the TROPION-Lung01 Trial Investigators, Gastón Lucas Martinengo, Juan Puig, Daniel Brungs, Bo Gao, Adnan Nagria, Christos S. Karapetis, Sagun Parakh, Cheol Park, Gaëtan Catala, Frédéric Forget, Sebahat Ocak, Naveen S. Basappa, Geoffrey Liu, Ines B. Menjak, Benjamin Shieh, Shun Lü, Feng Luo, Hongmei Sun, Jialei Wang, Yu Yao, Milada Zemanová, Jaafar Bennouna, Nicolas Girard, Laurent Greillier, Corinne Lamour, H. Léna, Céline Mascaux, Julien Mazières, Denis Moro‐Sibilot, M. Pérol, Elvire Pons‐Tostivint, Virginie Westeel, Akin Atmaca, Christine Greil, Niels Reinmuth, Christian Schumann, Thomas Wehler, Juergen Wolf, James Ho, Csaba Böcskei, Federico Cappuzzo, Filippo de Marinis, Claudia Proto, Manlio Mencoboni, Silvia Novello, Stefania Salvagni, Héctor Soto Parrà, Haruko Daga, Yasushi Goto, Hidetoshi Hayashi, Satoru Kitazono, Kiyotaka Yoh, Ryo Ko, Masashi Kondo, Toshiyuki Kozuki, Takayasu Kurata, Hideaki Mizutani, Kadoaki Ohashi, Satoshi Oizumi, Isamu Okamoto, Satoshi Sakaguchi, H Ozasa, Shunichi Sugawara, Yuichi Tambo, Motohiro Tamiya, Hiroshi Tanaka, Isamu Okamoto, Froylán López-López, Francisco Javier Ramírez Godinez, Jerónimo Rafael Rodríguez Cid, Robin Cornelissen, Steven Gans
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/m 2 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.