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PO007LBA/#1550  Efficacy and safety of trastuzumab deruxtecan in patients with HER2-expressing solid tumors: results from the cervical, endometrial, and ovarian cancer cohorts of the destiny-PanTumor02 study
  1. Jung-Yun Lee1,
  2. Vicky Makker2,3,
  3. Luis Manso4,
  4. Antonio González-Martín5,
  5. Iwona Ługowska6,
  6. Domenica Lorusso7,
  7. Susana Banerjee8,
  8. John Liao9,
  9. Chien-Hsing Lu10,
  10. Naiyarat Prasongsook11,
  11. Bohuslav Melichar12,
  12. Kai Chen13,
  13. Robert Mcewen14,
  14. Flavia Michelini15,
  15. Soham Puvvada14,
  16. Funda Meric-Bernstam16 and
  17. Ana Oaknin17
  1. 1Yonsei University College of Medicine, Obstetrics and Gynecology, Seoul, Korea, Republic of
  2. 2Memorial Sloan Kettering Cancer Center, Department of Medicine, New York, USA
  3. 3Weill Cornell Medical College, Department of Medicine, New York, USA
  4. 4Hospital Universitario 12 de Octubre, Department of Medical Oncology, Madrid, Spain
  5. 5Cancer Center Clínica Universidad de Navarra, Medical Oncology Department, and Programme In Solid Tumours-cima, Madrid, Spain
  6. 6Maria Skłodowska-Curie National Research Institute and Oncology Centre, Early Phase Clinical Trials Unit and Department of Soft Tissue/bone Sarcoma and Melanoma, Warsaw, Poland
  7. 7Fondazione Policlinico Gemelli and Catholic University of the Sacred Heart, Division of Gynecologic Oncology, Rome, Italy
  8. 8The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Gynaecology Unit, London, UK
  9. 9University of Washington, Division of Gynecologic Oncology, Seattle, USA
  10. 10Taichung Veterans General Hospital, Department of Obstetrics and Gynecology, Taichung, Taiwan
  11. 11Phramongkutklao Hospital, Medical Oncology Unit, Bangkok, Thailand
  12. 12University Hospital, Palacký University Medical School, Department of Oncology, Olomouc, Czech Republic
  13. 13AstraZeneca, Oncology Randd, Gaithersburg, USA
  14. 14AstraZeneca, Oncology Randd, Cambridge, UK
  15. 15AstraZeneca, Translational Medicine, Oncology Randd, Waltham, USA
  16. 16University of Texas MD Anderson Cancer Center, Department of Investigational Cancer Therapeutics, Houston, USA
  17. 17Vall d’Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus, Gynaecologic Cancer Programme, Barcelona, Spain


Introduction Trastuzumab deruxtecan (T-DXd) has demonstrated significant survival benefit for patients with HER2-expressing breast and gastric cancers. In DESTINY-PanTumor02, T-DXd demonstrated clinically meaningful response rates, progression-free survival (PFS), and overall survival (OS) in HER2-expressing tumors.

Methods This open-label, Phase 2 study (NCT04482309) evaluated T-DXd (5.4 mg/kg Q3W) in patients across seven cohorts with HER2-expressing (immunohistochemistry [IHC] 3+/2+ by local [with retrospective central testing] or central testing) locally advanced/metastatic disease after ≥1 systemic treatment, or without alternative treatment. The primary endpoint was investigator-assessed confirmed objective response rate (ORR). Secondary endpoints included duration of response, PFS, OS, and safety. Exploratory endpoints included pharmacodynamic biomarkers.

Results At data cutoff (June 2023), 120 patients in the endometrial, cervical, and ovarian cancer cohorts had received treatment (median follow-up [range]: 19.94 [0.8–31.1], 12.60 [0.9–31.0], and 13.13 [0.7–30.6] months, respectively). Overall, 80.8% received ≥2 prior lines of therapy. Table 1 shows efficacy outcomes by HER2 expression levels by cohort. Table 2 shows ORR by HER2 in situ hybridization (ISH) amplification and plasma HER2 amplification by cohort. Grade (G)≥3 drug-related adverse events occurred in 54/120 (45.0%) patients; adjudicated treatment-related interstitial lung disease/pneumonitis occurred in 13/120 (10.8%) patients (n=12 G≤2; n=1 G5).

Conclusion/Implications T-DXd demonstrated clinically meaningful benefit, including responses across HER2 expression levels and in ISH+ or plasma ERBB2 amplified subgroups, and encouraging survival outcomes in patients with gynecological tumors. Safety was consistent with the known profile. These data support T-DXd as a potential treatment for patients with gynecological HER2-expressing tumors who progressed on prior therapy.

Abstract PO007LBA/#1550 Table 1
Abstract PO007LBA/#1550 Table 2

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