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: 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 ,   for the TROPION-Lung01 Trial Investigators, Martinengo Gaston Lucas , Puig Juan , Brungs Daniel , Gao Bo , Nagria Adnan , Karapetis Chris , Parakh Sagun , Park John , Catala Gaetan , Forget Frederic , Ocak Sebahat , Basappa Naveen , Liu Geoffrey , Menjak Ines , Shieh Benjamin , Lu Shun , Luo Feng , Sun Hongmei , Wang Jialei , Yao Yu , Zemanova Milada , Bennouna Jaafar , Girard Nicolas , Greillier Laurent , Lamour Corinne , Lena Herve , Mascaux Céline , Mazieres Julien , Moro-Sibilot Denis , Pérol Maurice , Pons-Tostivint Elvire , Westeel Virginie , Atmaca Akin , Greil Christine , Reinmuth Niels , Schumann Christian , Wehler Thomas , Wolf Juergen , Ho James , Bocskei Csaba , Cappuzzo Federico , de Marinis Filippo , Proto Claudia , Mencoboni Manlio , Novello Silvia , Salvagni Stefania , Parra Hector Soto , Daga Haruko , Goto Yasushi , Hayashi Hidetoshi , Kitazono Satoru , Yoh Kiyotaka , Ko Ryo , Kondo Masashi , Kozuki Toshiyuki , Kurata Takayasu , Mizutani Hideaki , Ohashi Kadoaki , Oizumi Satoshi , Okamoto Isamu , Sakaguchi Satoshi , Ozasa Hiroaki , Sugawara Shunichi , Tambo Yuichi , Tamiya Motohiro , Tanaka Hiroshi , Okamoto Isamu , Lopez-Lopez Froylan , Ramirez Godinez Francisco Javier , Rodriguez Cid Jeronimo Rafael , Cornelissen Robin , Gans Steven , Stigt Jos , Kowalski Dariusz , Lowczak Anna , Milanowski Janusz , Mróz Robert , Ramlau Rodryg , Acosta-Rivera Mirelis , Ahn Myung-Ju , Chae Yee Soo , Hong Min Hee , Kang Jin-Hyoung , Kim Sang-We , Kim Jin-Soo , Kim Se Hyun , Lee Ki Hyeong , Lee Yun Gyoo , Shim Byoung Yong , Ledin Evgeniy , Poddubskaya Elena , Daniel Chan Boon Yeow , Jain Amit , Tan Chee Seng , Areses Maria Carmen , Cobo Manuel , Domine Manuel , Felip Enriqueta , Pradera José Fuentes , Isla Dolores , Vidal Oscar Juan , Majem Margarita , Paz-Ares Luis , Provencio Mariano , Reguart Noemi , Baz David Vicente , Cerciello Ferdinando , Früh Martin , Chang Wen-Cheng , Chang Gee-Chen , Huang Wen-Tsung , Ling Chien-Chung , Wei Yu-Feng , Yang Tsung-Ying , Ahmad Tanya , Gomes Fabio , Mansy Talal , Bruno Debora , Castine Michael , Fang Bruno , Garassino Marina , Hall Richard , Halmos Balazs , Jahangir Khawaja , Johnson Melissa , Johnson Tirrell , Kalmadi Sujith , Lawler William , Lisberg Aaron , Sadiq Ahad , Sands Jacob , Solomon Benjamin , Veatch Andrea 
Published: September 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.