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

Author:

Ahn Myung-Ju1ORCID,Tanaka Kentaro2ORCID,Paz-Ares Luis3ORCID,Cornelissen Robin4ORCID,Girard Nicolas5ORCID,Pons-Tostivint Elvire6ORCID,Vicente Baz David7,Sugawara Shunichi8ORCID,Cobo Manuel9ORCID,Pérol Maurice10ORCID,Mascaux Céline11ORCID,Poddubskaya Elena12ORCID,Kitazono Satoru13ORCID,Hayashi Hidetoshi14ORCID,Hong Min Hee15ORCID,Felip Enriqueta16ORCID,Hall Richard17ORCID,Juan-Vidal Oscar18ORCID,Brungs Daniel19ORCID,Lu Shun20ORCID,Garassino Marina21ORCID,Chargualaf Michael22ORCID,Zhang Yong22ORCID,Howarth Paul22ORCID,Uema Deise22ORCID,Lisberg Aaron23ORCID,Sands Jacob24ORCID, ,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

Affiliation:

1. Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

2. Kyushu University Hospital, Fukuoka, Japan

3. Hospital Universitario 12 de Octubre, Madrid, Spain

4. Erasmus MC Cancer Institute, Rotterdam, the Netherlands

5. Institut Curie, Paris, France

6. University Hospital of Nantes, Nantes, France

7. Hospital Universitario Virgen Macarena, Seville, Spain

8. Sendai Kousei Hospital, Sendai, Japan

9. Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria University Hospitals, IBIMA, Málaga, Spain

10. Centre Léon Bérard, Lyon, France

11. Hopitaux Universitaire de Strasbourg, Strasbourg, France

12. VitaMed LLC, Moscow, Russia

13. The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan

14. Kindai University Hospital, Osaka, Japan

15. Yonsei Cancer Center, Severance Hospital, Seoul, Republic of Korea

16. Vall d’Hebron Hospital Campus, Vall d’Hebron Institute of Oncology, Universitat Autònoma de Barcelona, Spain

17. University of Virginia Health System, Charlottesville, VA

18. Hospital Universitari i Politecnic La Fe, Valencia, Spain

19. Southern Medical Day Care Centre, University of Wollongong, Wollongong, Australia

20. Shanghai Lung Cancer Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

21. Department of Medicine, Hematology-Oncology Section, Thoracic Oncology Program, The University of Chicago Medicine & Biological Sciences, Chicago, IL

22. Daiichi Sankyo, Basking Ridge, NJ

23. Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA

24. Dana-Farber Cancer Institute, Boston, MA

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.

Publisher

American Society of Clinical Oncology (ASCO)

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