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, Gaston Lucas Martinengo, Juan Puig, Daniel Brungs, Bo Gao, Adnan Nagria, Chris Karapetis, Sagun Parakh, John Park, Gaetan Catala, Frederic Forget, Sebahat Ocak, Naveen Basappa, Geoffrey Liu, Ines Menjak, Benjamin Shieh, Shun Lu, Feng Luo, Hongmei Sun, Jialei Wang, Yu Yao, Milada Zemanova, Jaafar Bennouna, Nicolas Girard, Laurent Greillier, Corinne Lamour, Herve Lena, Céline Mascaux, Julien Mazieres, Denis Moro-Sibilot, Maurice Pérol, Elvire Pons-Tostivint, Virginie Westeel, Akin Atmaca, Christine Greil, Niels Reinmuth, Christian Schumann, Thomas Wehler, Juergen Wolf, James Ho, Csaba Bocskei, Federico Cappuzzo, Filippo de Marinis, Claudia Proto, Manlio Mencoboni, Silvia Novello, Stefania Salvagni, Hector Soto Parra, 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, Hiroaki Ozasa, Shunichi Sugawara, Yuichi Tambo, Motohiro Tamiya, Hiroshi Tanaka, Isamu Okamoto, Froylan Lopez-Lopez, Francisco Javier Ramirez Godinez, Jeronimo Rafael Rodriguez Cid, Robin Cornelissen, Steven Gans, Jos Stigt, Dariusz Kowalski, Anna Lowczak, Janusz Milanowski, Robert Mróz, Rodryg Ramlau, Mirelis Acosta-Rivera, Myung-Ju Ahn, Yee Soo Chae, Min Hee Hong, Jin-Hyoung Kang, Sang-We Kim, Jin-Soo Kim, Se Hyun Kim, Ki Hyeong Lee, Yun Gyoo Lee, Byoung Yong Shim, Evgeniy Ledin, Elena Poddubskaya, Boon Yeow Daniel Chan, Amit Jain, Chee Seng Tan, Maria Carmen Areses, Manuel Cobo, Manuel Domine, Enriqueta Felip, José Fuentes Pradera, Dolores Isla, Oscar Juan Vidal, Margarita Majem, Luis Paz-Ares, Mariano Provencio, Noemi Reguart, David Vicente Baz, Ferdinando Cerciello, Martin Früh, Wen-Cheng Chang, Gee-Chen Chang, Wen-Tsung Huang, Chien-Chung Ling, Yu-Feng Wei, Tsung-Ying Yang, Tanya Ahmad, Fabio Gomes, Talal Mansy, Debora Bruno, Michael Castine, Bruno Fang, Marina Garassino, Richard Hall, Balazs Halmos, Khawaja Jahangir, Melissa Johnson, Tirrell Johnson, Sujith Kalmadi, William Lawler, Aaron Lisberg, Ahad Sadiq, Jacob Sands, Benjamin Solomon, Andrea Veatch
Journal: Journal of Clinical Oncology (2024)

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.