TY - JOUR
T1 - Antitumor activity and safety of trastuzumab deruxtecan in patients with HER2-low–expressing advanced breast cancer
T2 - Results from a phase Ib study
AU - Modi, Shanu
AU - Park, Haeseong
AU - Murthy, Rashmi K.
AU - Iwata, Hiroji
AU - Tamura, Kenji
AU - Tsurutani, Junji
AU - Moreno-Aspitia, Alvaro
AU - Doi, Toshihiko
AU - Sagara, Yasuaki
AU - Redfern, Charles
AU - Krop, Ian E.
AU - Lee, Caleb
AU - Fujisaki, Yoshihiko
AU - Sugihara, Masahiro
AU - Zhang, Lin
AU - Shahidi, Javad
AU - Takahashi, Shunji
N1 - Publisher Copyright:
© 2020 by American Society of Clinical Oncology.
PY - 2020
Y1 - 2020
N2 - PURPOSE Trastuzumab deruxtecan (T-DXd, formerly DS-8201a) is a novel human epidermal growth factor receptor 2 (HER2)-targeted antibody drug conjugate (ADC) with a topoisomerase I inhibitor payload. A dose escalation and expansion phase I study evaluated the safety and activity of T-DXd in patients with advanced HER2-expressing/mutated solid tumors. Here, results for T-DXd at the recommended doses for expansion (RDE) in patients with HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/in situ hybridization2) breast cancer (ClinicalTrials.gov identifier: NCT02564900) are reported. PATIENTS AND METHODS Eligible patients had advanced/metastatic HER2-low–expressing breast cancer refractory to standard therapies. The RDE of 5.4 or 6.4 mg/kg T-DXd were administered intravenously once every 3 weeks until withdrawal of consent, unacceptable toxicity, or progressive disease. Antitumor activity and safety were assessed. RESULTS Between August 2016 and August 2018, 54 patients were enrolled and received $ 1 dose of T-DXd at the RDE. Patients were extensively pretreated (median, 7.5 prior therapies). The confirmed objective response rate by independent central review was 20/54 (37.0%; 95% CI, 24.3% to 51.3%) with median duration of response of 10.4 months (95% CI, 8.8 month to not evaluable). Most patients (53/54; 98.1%) experienced $ 1 treatment-emergent adverse event (TEAE; grade $ 3; 34/54; 63.0%). Common ($ 5%) grade $ 3 TEAEs included decreases in neutrophil, platelet, and WBC counts; anemia; hypokalemia; AST increase; decreased appetite; and diarrhea. Three patients treated at 6.4 mg/kg suffered fatal events associated with T-DXd–induced interstitial lung disease (ILD)/pneumonitis as determined by an independent adjudication committee. CONCLUSION The novel HER2-targeted ADC, T-DXd, demonstrated promising preliminary antitumor activity in patients with HER2-low breast cancer. Most toxicities were GI or hematologic in nature. ILD is an important identified risk and should be monitored closely and proactively managed.
AB - PURPOSE Trastuzumab deruxtecan (T-DXd, formerly DS-8201a) is a novel human epidermal growth factor receptor 2 (HER2)-targeted antibody drug conjugate (ADC) with a topoisomerase I inhibitor payload. A dose escalation and expansion phase I study evaluated the safety and activity of T-DXd in patients with advanced HER2-expressing/mutated solid tumors. Here, results for T-DXd at the recommended doses for expansion (RDE) in patients with HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/in situ hybridization2) breast cancer (ClinicalTrials.gov identifier: NCT02564900) are reported. PATIENTS AND METHODS Eligible patients had advanced/metastatic HER2-low–expressing breast cancer refractory to standard therapies. The RDE of 5.4 or 6.4 mg/kg T-DXd were administered intravenously once every 3 weeks until withdrawal of consent, unacceptable toxicity, or progressive disease. Antitumor activity and safety were assessed. RESULTS Between August 2016 and August 2018, 54 patients were enrolled and received $ 1 dose of T-DXd at the RDE. Patients were extensively pretreated (median, 7.5 prior therapies). The confirmed objective response rate by independent central review was 20/54 (37.0%; 95% CI, 24.3% to 51.3%) with median duration of response of 10.4 months (95% CI, 8.8 month to not evaluable). Most patients (53/54; 98.1%) experienced $ 1 treatment-emergent adverse event (TEAE; grade $ 3; 34/54; 63.0%). Common ($ 5%) grade $ 3 TEAEs included decreases in neutrophil, platelet, and WBC counts; anemia; hypokalemia; AST increase; decreased appetite; and diarrhea. Three patients treated at 6.4 mg/kg suffered fatal events associated with T-DXd–induced interstitial lung disease (ILD)/pneumonitis as determined by an independent adjudication committee. CONCLUSION The novel HER2-targeted ADC, T-DXd, demonstrated promising preliminary antitumor activity in patients with HER2-low breast cancer. Most toxicities were GI or hematologic in nature. ILD is an important identified risk and should be monitored closely and proactively managed.
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U2 - 10.1200/JCO.19.02318
DO - 10.1200/JCO.19.02318
M3 - Article
C2 - 32058843
AN - SCOPUS:85081268424
SN - 0732-183X
VL - 38
SP - 1887
EP - 1896
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 17
ER -