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(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

Source: https://doi.org/10.1200/JCO-24-01544

Dr. Anjan Patel's Thoughts

Positive trial for the newest ADC on the block, Dato-DXd, is an ADC that delivers a topoisomerase I inhibitor payload via a TROP2 antibody. PFS was not impressive but favored DDxd at 4.4 vs 3.7 months in the docetaxel arm. This drug is now approved in metastatic breast cancer.

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

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